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Probiotics Emerge as Promising Intervention in Cirrhosis
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
, according to a systematic review and meta-analysis.
They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.
“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.
“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”
The study was published online in Frontiers in Medicine .
Analyzing Probiotic Trials
The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.
The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.
Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.
In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.
Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.
Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).
Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.
“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
Considering Variables
The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.
“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.
“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”
Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.
“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”
However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.
“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.
The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.
A version of this article appeared on Medscape.com .
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and r</metaDescription> <articlePDF/> <teaserImage/> <teaser>“The study shows that probiotics can improve some disease markers in cirrhosis,” said Dr. Phillipp Hartmann.</teaser> <title>Probiotics Emerge as Promising Intervention in Cirrhosis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> <term>213</term> <term>226</term> <term>49620</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Probiotics Emerge as Promising Intervention in Cirrhosis</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Probiotics appear to be beneficial for patients with <span class="Hyperlink">cirrhosis</span>, showing a reversal of <span class="Hyperlink">hepatic encephalopathy</span> (HE), improvement in liver function measures, and regulation of gut dysbiosis</span>, according to a systematic review and meta-analysis.</p> <p>They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.<br/><br/>“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.<br/><br/>“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”<br/><br/>The study was <a href="https://www.frontiersin.org/articles/10.3389/fmed.2024.1379333/full">published online</a> in <em>Frontiers in Medicine</em> .<br/><br/></p> <h2>Analyzing Probiotic Trials</h2> <p>The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.</p> <p>The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.<br/><br/>Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains <em>Streptococcus</em>, <em>Bifidobacterium</em>, and <em>Lactobacillus</em> — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.<br/><br/>In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.<br/><br/>Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for <em>Bifidobacterium</em>, <em>Enterococcus</em>, <em>Bacteroidaceae</em>, and <em>Fusobacterium</em>.<br/><br/>Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).<br/><br/>Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.<br/><br/>“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”<br/><br/></p> <h2>Considering Variables</h2> <p>The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.</p> <p>“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.<br/><br/>“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”<br/><br/>Dr. Hartmann, who wasn’t involved with this study, has <span class="Hyperlink"><a href="https://journals.physiology.org/doi/abs/10.1152/ajpgi.00017.2023">published a review</a></span> on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.<br/><br/>“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”<br/><br/>However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.<br/><br/>“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.<br/><br/>The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.</p> <p> <em> <span class="Emphasis">A version of this article appeared on </span> <span class="Hyperlink"> <a href="https://www.medscape.com/viewarticle/probiotics-emerge-promising-intervention-cirrhosis-2024a10008g7">Medscape.com</a> </span> <span class="Emphasis">.</span> </em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
May 2024 – ICYMI
Gastroenterology
January 2024
Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.
Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.
Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.
February 2024
Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.
Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.
Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
Clinical Gastroenterology and Hepatology
January 2024
Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.
Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.
Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.
February 2024
Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.
Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
Techniques and Innovations in Gastrointestinal Endoscopy
January 2024
Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.
Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.
Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
Gastro Hep Advances
January 2024
Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.
Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.
Gastroenterology
January 2024
Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.
Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.
Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.
February 2024
Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.
Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.
Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
Clinical Gastroenterology and Hepatology
January 2024
Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.
Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.
Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.
February 2024
Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.
Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
Techniques and Innovations in Gastrointestinal Endoscopy
January 2024
Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.
Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.
Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
Gastro Hep Advances
January 2024
Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.
Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.
Gastroenterology
January 2024
Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.
Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.
Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.
February 2024
Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.
Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.
Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
Clinical Gastroenterology and Hepatology
January 2024
Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.
Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.
Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.
February 2024
Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.
Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
Techniques and Innovations in Gastrointestinal Endoscopy
January 2024
Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.
Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.
Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
Gastro Hep Advances
January 2024
Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.
Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>In case you missed it: Recent studies published in the journals of the American Gastroenterology Association.</metaDescription> <articlePDF/> <teaserImage/> <teaser> <span class="tag metaDescription">In case you missed it: Recent studies published in the journals of the American Gastroenterology Association.</span> </teaser> <title>May 2024 – ICYMI</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> </publications> <sections> <term>47431</term> <term canonical="true">46646</term> </sections> <topics> <term canonical="true">347</term> <term>344</term> <term>345</term> <term>39703</term> <term>39702</term> <term>343</term> <term>346</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>May 2024 – ICYMI</title> <deck/> </itemMeta> <itemContent> <h2>Gastroenterology</h2> <p> <strong>January 2024</strong> </p> <p>Hirano I, et al; ASCENT WORKING GROUP. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.09.004">Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis</a></span>. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.<br/><br/><br/><br/>Åkerström JH, et al. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.08.050">Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus</a></span>. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.<br/><br/><br/><br/>Barnes EL, et al; AGA Clinical Guidelines Committee. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.10.015">AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders</a></span>. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.</p> <p><strong>February 2024</strong><br/><br/>Yoo HW, et al. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.10.013">Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study</a></span>. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.<br/><br/><br/><br/>Yang J, et al. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.10.012">High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice</a></span>. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.<br/><br/><br/><br/>Young E, et al. <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2023.10.008">Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial</a></span>. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.<br/><br/></p> <h2>Clinical Gastroenterology and Hepatology</h2> <p><strong>January 2024</strong><br/><br/>Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.cgh.2023.03.035">Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk</a></span>. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.</p> <p><br/><br/>Reddy CA, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.cgh.2023.06.013">Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders</a></span>. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.<br/><br/>Thiruvengadam NR, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.cgh.2023.05.028">The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis</a></span>. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.</p> <p><strong>February 2024</strong><br/><br/>Goodoory VC, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.cgh.2023.02.014">Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome</a></span>. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.<br/><br/>Brenner DM, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.cgh.2023.09.013">Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome</a></span>. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.<br/><br/></p> <h2>Techniques and Innovations in Gastrointestinal Endoscopy</h2> <p><strong>January 2024</strong><br/><br/>Ramirez PR, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.tige.2023.10.001">Gaps and Improvement Opportunities in Post-Colonoscopy Communication</a></span>. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.</p> <p><br/><br/>Gonzaga ER, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.tige.2023.09.002">Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis</a></span>. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.<br/><br/><br/><br/>Wang D, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.tige.2023.10.003">Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis</a></span>. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.<br/><br/></p> <h2>Gastro Hep Advances</h2> <p><strong>January 2024</strong><br/><br/>Adeniran E, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.gastha.2023.08.017">Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention</a></span>. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.</p> <p><br/><br/>Alkhouri N, et al. <span class="Hyperlink"><a href="https://doi.org/10.1016/j.gastha.2023.08.019">A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease</a></span>. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Artificial Intelligence in GI and Hepatology
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
Dear colleagues,
Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.
In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.
Artificial Intelligence in Gastrointestinal Endoscopy
BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD
The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.
Approved applications for colorectal cancer
In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).1-3
Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.4 Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.5
Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.6 In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.7 The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.
Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.
Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.
Innovative applications for alternative gastrointestinal conditions
Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.
Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.11 Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.
Artificial intelligence adoption in clinical practice
Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.
Conclusions
Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.
Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.
References
1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.
2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.
3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.
4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.
5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.
6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.
7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.
8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.
9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.
10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.
11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.
12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.
13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.
The Promise and Challenges of AI in Hepatology
BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL
In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.
The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.
Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.
AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.
Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.
Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.
In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.
We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.
Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.
Sources
Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.
Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.
Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.
Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167656</fileName> <TBEID>0C04F83D.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F83D</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>Perspectives for May GIHEP</storyname> <articleType>353</articleType> <TBLocation>Published-All Pubs</TBLocation> <QCDate/> <firstPublished>20240503T152711</firstPublished> <LastPublished>20240503T153001</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240503T152711</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>McCarty, Nabil, Mansour</byline> <bylineText/> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Dear colleagues,Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. E</metaDescription> <articlePDF/> <teaserImage>300209</teaserImage> <teaser>As the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.</teaser> <title>Artificial Intelligence in GI and Hepatology</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>2</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> </publications> <sections> <term canonical="true">41022</term> <term>52</term> </sections> <topics> <term canonical="true">346</term> <term>39702</term> <term>343</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012632.jpg</altRep> <description role="drol:caption">Dr. Nabil M. Mansour</description> <description role="drol:credit">Baylor College of Medicine</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012818.jpg</altRep> <description role="drol:caption">Dr. Basile Njei</description> <description role="drol:credit">Yale School of Medicine</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012817.jpg</altRep> <description role="drol:caption">Yazan A. Al-Ajlouni</description> <description role="drol:credit">New York Medical College</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Artificial Intelligence in GI and Hepatology</title> <deck/> </itemMeta> <itemContent> <p><em>Dear colleagues,</em><br/><br/>Since <span class="Hyperlink"><a href="https://gastro.org/news/innovation-in-gi-whats-the-next-big-thing/">our prior Perspectives piece</a></span> on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.</p> <p>In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X <span class="Hyperlink"><a href="https://twitter.com/AGA_GIHN">@AGA_GIHN</a></span>.</p> <p> <em>Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.</em> </p> <h2>Artificial Intelligence in Gastrointestinal Endoscopy</h2> <p><strong>BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD</strong><br/><br/>The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.[[{"fid":"300209","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Nabil M. Mansour, McNair General GI Clinic at Baylor College of Medicine in Houston","field_file_image_credit[und][0][value]":"Baylor College of Medicine","field_file_image_caption[und][0][value]":"Dr. Nabil M. Mansour"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/><strong>Approved applications for colorectal cancer</strong><br/><br/>In an attempt to improve colorectal cancer screening and outcomes related to screening and surveillance, efforts have been focused on procedural performance metrics, quality indicators, and tools to aid in lesion detection and improve quality of care. One such tool has been computer-aided detection (CADe), with early randomized controlled trial (RCT) data showing significantly increased adenoma detection rate (ADR) and adenomas per colonoscopy (APC).<sup>1-3</sup> </p> <p>Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.<sup>4</sup> Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.<sup>5</sup><br/><br/>Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.<sup>6</sup> In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.<sup>7</sup> The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.<br/><br/>Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.<br/><br/>Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.</p> <p><strong>Innovative applications for alternative gastrointestinal conditions</strong><br/><br/>Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases. </p> <p>Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.<sup>8-10</sup> Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.<sup>11</sup> Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.<sup>12,13</sup> Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.</p> <p><strong>Artificial intelligence adoption in clinical practice</strong><br/><br/>Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required. <br/><br/><strong>Conclusions</strong><br/><br/>Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.<span class="end"/></p> <p> <em>Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.</em> </p> <h2>References</h2> <p>1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2020.04.062">10.1053/j.gastro.2020.04.062</a></span>.<br/><br/>2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: <span class="Hyperlink"><a href="https://gut.bmj.com/content/71/4/757">10.1136/gutjnl-2021-324471</a></span>.<br/><br/>3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2022.03.007">10.1053/j.gastro.2022.03.007</a></span>.<br/><br/>4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: <span class="Hyperlink"><a href="https://www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf">www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf</a></span>.<br/><br/>5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: <span class="Hyperlink"><a href="https://www.thelancet.com/journals/landig/article/PIIS2589-7500(23)00242-X/fulltext">10.1016/S2589-7500(23)00242-X</a></span>. <br/><br/>6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: <span class="Hyperlink"><a href="https://doi.org/10.1053/j.gastro.2022.12.004">10.1053/j.gastro.2022.12.004</a></span>. <br/><br/>7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: <span class="Hyperlink"><a href="https://journals.lww.com/ajg/abstract/2023/10000/evaluation_of_computer_aided_detection_during.28.aspx">10.14309/ajg.0000000000002239</a></span>. <br/><br/>8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: <span class="Hyperlink"><a href="https://onlinelibrary.wiley.com/doi/10.1177/2050640619837443">10.1177/2050640619837443</a></span>. <br/><br/>9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: <span class="Hyperlink"><a href="https://doi.org/10.1016/j.gie.2017.11.029">10.1016/j.gie.2017.11.029</a></span>. <br/><br/>10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: <span class="Hyperlink"><a href="https://www.nature.com/articles/s41598-022-17502-7">10.1038/s41598-022-17502-7</a></span>. <br/><br/>11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: <span class="Hyperlink"><a href="https://doi.org/10.20524/aog.2023.0779">10.20524/aog.2023.0779</a></span>. <br/><br/>12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: <span class="Hyperlink"><a href="https://gut.bmj.com/content/71/12/2388">10.1136/gutjnl-2021-326470</a></span>.<br/><br/>13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: <span class="Hyperlink"><a href="https://www.nature.com/articles/s41467-023-42451-8">10.1038/s41467-023-42451-8</a></span>. </p> <h2>The Promise and Challenges of AI in Hepatology</h2> <p><strong>BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL</strong><br/><br/>In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.</p> <p>The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.<br/><br/>[[{"fid":"301101","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Basile Njei, Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn.","field_file_image_credit[und][0][value]":"Yale School of Medicine","field_file_image_caption[und][0][value]":"Dr. Basile Njei"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research. <br/><br/>AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.<br/><br/>[[{"fid":"301100","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Yazan A. Al-Ajlouni, senior medical student at New York Medical College School of Medicine, Valhalla, N.Y.","field_file_image_credit[und][0][value]":"New York Medical College","field_file_image_caption[und][0][value]":"Yazan A. Al-Ajlouni"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.<br/><br/>Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.<br/><br/>In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future. <br/><br/>We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.<span class="end"/></p> <p> <em>Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.</em> </p> <h2>Sources</h2> <p>Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: <span class="Hyperlink"><a href="https://journals.lww.com/hep/toc/2021/07000">10.1002/hep.31750</a></span>.<br/><br/>Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: <span class="Hyperlink"><a href="https://doi.org/10.1016/j.jhep.2022.01.018">10.1016/j.jhep.2022.01.018</a></span>.<br/><br/>Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: <span class="Hyperlink"><a href="https://journals.lww.com/ajg/toc/2022/03000">10.14309/ajg.0000000000001617</a></span>.<br/><br/>Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: <span class="Hyperlink"><a href="https://www.cureus.com/articles/187909-the-application-of-artificial-intelligence-ai-based-ultrasound-for-the-diagnosis-of-fatty-liver-disease-a-systematic-review#!/">10.7759/cureus.50601</a></span>.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Real-World HDV Study Characterizes Responses to Bulevirtide
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167499</fileName> <TBEID>0C04F4EC.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F4EC</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>GHA_Killer_HDV</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240409T153350</QCDate> <firstPublished>20240409T154337</firstPublished> <LastPublished>20240409T154337</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240409T154336</CMSDate> <articleSource>FROM GASTRO HEP ADVANCES </articleSource> <facebookInfo/> <meetingNumber/> <byline>Will Pass</byline> <bylineText>WILL PASS</bylineText> <bylineFull>WILL PASS</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Some hepatitis D virus (HDV)-infected patients may require longer treatment with bulevirtide than others, but even “nonresponders” according to US Food and Drug</metaDescription> <articlePDF/> <teaserImage>301066</teaserImage> <teaser>The findings suggest that longer follow-up is needed to determine optimal treatment duration for bulevirtide monotherapy.</teaser> <title>Real-World HDV Study Characterizes Responses to Bulevirtide</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> </publications> <sections> <term canonical="true">69</term> <term>27970</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240127f0.jpg</altRep> <description role="drol:caption">Dr. Alexander Killer</description> <description role="drol:credit">Heinrich Heine University</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Real-World HDV Study Characterizes Responses to Bulevirtide</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Some hepatitis D virus (HDV)-infected patients may require longer treatment with bulevirtide than others, but even “nonresponders” according to US Food and Drug Administration (FDA) criteria may achieve reduced viremia with ALT normalization</span>, based on real-world experience.</p> <p>These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author <a href="https://www.researchgate.net/profile/Alexander-Killer">Alexander Killer, MD</a>, of Heinrich Heine University Düsseldorf, Germany, and colleagues.<br/><br/>[[{"fid":"301066","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Alexander Killer, Heinrich Heine University Düsseldorf, Germany","field_file_image_credit[und][0][value]":"Heinrich Heine University","field_file_image_caption[und][0][value]":"Dr. Alexander Killer"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is <a href="https://www.gilead.com/news-and-press/press-room/press-releases/2023/5/chmp-adopts-positive-opinion-recommending-hepcludex-bulevirtide-for-full-marketing-authorization-for-the-treatment-of-hepatitis-delta-virus-hdv">on track for full marketing approval</a> in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced <a href="https://www.gilead.com/news-and-press/company-statements/gilead-receives-complete-response-letter-from-us-fda-for-bulevirtide-for-the-treatment-of-adults-with-hepatitis-delta-virus">regulatory hurdles</a>. <br/><br/>In the <a href="https://www.sciencedirect.com/science/article/abs/pii/S1473309922003188">MYR202</a> and <a href="https://www.nejm.org/doi/10.1056/NEJMoa2213429">301</a> clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks. <br/><br/>“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues <span class="Hyperlink"><a href="https://www.ghadvances.org/article/S2772-5723(24)00001-3/fulltext">wrote</a></span> in <em>Gastro Hep Advances</em>.<br/><br/>Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany. <br/><br/>The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.<br/><br/>Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting. <br/><br/>Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.<br/><br/>“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.<br/><br/>Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.<br/><br/>Of note, two patients had ALT normalization without virologic response.<br/><br/>“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”<br/><br/>The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.<br/><br/>This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM GASTRO HEP ADVANCES
FDA Approves First Drug for MASH
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release.
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release.
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167330</fileName> <TBEID>0C04F10A.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F10A</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240321T112415</QCDate> <firstPublished>20240321T120021</firstPublished> <LastPublished>20240321T120021</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240321T120020</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Megan Brooks</byline> <bylineText>MEGAN BROOKS</bylineText> <bylineFull>MEGAN BROOKS</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunc</metaDescription> <articlePDF/> <teaserImage>221080</teaserImage> <teaser>Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist.</teaser> <title>FDA Approves First Drug for MASH</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> <term>21</term> <term>15</term> </publications> <sections> <term>39313</term> <term canonical="true">27979</term> </sections> <topics> <term>213</term> <term>226</term> <term canonical="true">346</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400a061.jpg</altRep> <description role="drol:caption">Dr. Stephen Harrison</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>FDA Approves First Drug for MASH</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease)</span>, along with diet and exercise. </p> <p>Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.<br/><br/>The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. <br/><br/>The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) <br/><br/>The results were <a href="https://www.nejm.org/doi/10.1056/NEJMoa2309000">published online</a> February 6 in <em>The New England Journal of Medicine</em>. <br/><br/>“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a <a href="https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-fda-approval-rezdiffratm">news release</a>. <br/><br/>[[{"fid":"221080","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Stephen Harrison, medical director of Pinnacle Clinical Research","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Stephen Harrison"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.<br/><br/> </p> <h2>Addressing an Unmet Need </h2> <p>MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. </p> <p>In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. <br/><br/>Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.<br/><br/>Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. <br/><br/>At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.<br/><br/>Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. <br/><br/>The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. <br/><br/>Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. <br/><br/>The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.<br/><br/>Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.<br/><br/>Full prescribing information is <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217785s000lbl.pdf">available online</a>. Prescribing information does not include a liver biopsy requirement for diagnosis.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/fda-approves-first-drug-mash-2024a10004vn">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Semaglutide Curbs MASLD Severity in People Living With HIV
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, ac</metaDescription> <articlePDF/> <teaserImage/> <teaser>Most participants lost significant weight and weight loss was closely associated with improvements in MASLD.</teaser> <title>Semaglutide Curbs MASLD Severity in People Living With HIV</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>idprac</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term>34</term> <term>15</term> <term canonical="true">21</term> <term>20</term> </publications> <sections> <term>53</term> <term canonical="true">39313</term> </sections> <topics> <term>239</term> <term>205</term> <term canonical="true">226</term> <term>261</term> <term>318</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Semaglutide Curbs MASLD Severity in People Living With HIV</title> <deck/> </itemMeta> <itemContent> <p>Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s <a href="https://www.medscape.com/viewcollection/37447">Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting</a> in Denver.</p> <p>Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.<br/><br/></p> <h2>‘A First’</h2> <p>SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.</p> <p>The phase 2b, single-arm <a href="https://www.clinicaltrials.gov/study/NCT04216589">pilot study</a> enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.<br/><br/>Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.<br/><br/>The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.<br/><br/>A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.<br/><br/>In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.<br/><br/>Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.<br/><br/>The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.<br/><br/>Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.<br/><br/>The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.<br/><br/>All participants completed the full 24 weeks of therapy at the originally prescribed dose.<br/><br/></p> <h2>Potential Impact</h2> <p>“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”</p> <p>“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.<br/><br/>The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.<br/><br/>No conflicts of interest were reported.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/semaglutide-curbs-masld-severity-people-living-hiv-2024a10004jq?src=">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM CROI 2024
Seladelpar Could ‘Raise the Bar’ in Primary Biliary Cholangitis Treatment
, according to the full results of the RESPONSE phase 3 study.
“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.
The study data are “genuinely exciting...and support the potential for seladelpar to raise the bar in PBC treatment,” Dr. Hirschfield added in a news release.
Seladelpar is being developed by CymaBay Therapeutics, which funded the study.
The results were published online in The New England Journal of Medicine.
Topline data from the study were presented in November at The Liver Meeting 2023: American Association for the Study of Liver Diseases.
‘Unequivocal’ Progress
Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.
Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.
In the RESPONSE study, 193 patients with PBC who had an inadequate response to or a history of unacceptable side effects with UDCA were randomly allocated to either oral seladelpar 10 mg daily or placebo for 12 months. The vast majority (93.8%) continued UDCA as standard-of-care background therapy.
The primary endpoint was a biochemical response, which was defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at 12 months.
After 12 months, 61.7% of patients taking seladelpar met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking seladelpar than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the seladelpar group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the seladelpar group compared with 6.5% and 11.4%, respectively, in the placebo group.
“In PBC, we use target endpoints, so the trial was not powered or able to show yet clinical outcomes because the pace of the disease is quite slow. But we believe that the normalization of liver tests and improvement in quality of life will change the disease trajectory over time,” Dr. Hirschfield said.
Significant Reduction in Pruritus
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.
Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.
“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.
The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.
The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
Potential First-Line Treatment?
In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”
“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.
“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.
Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.
“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.
Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.
The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, according to the full results of the RESPONSE phase 3 study.
“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.
The study data are “genuinely exciting...and support the potential for seladelpar to raise the bar in PBC treatment,” Dr. Hirschfield added in a news release.
Seladelpar is being developed by CymaBay Therapeutics, which funded the study.
The results were published online in The New England Journal of Medicine.
Topline data from the study were presented in November at The Liver Meeting 2023: American Association for the Study of Liver Diseases.
‘Unequivocal’ Progress
Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.
Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.
In the RESPONSE study, 193 patients with PBC who had an inadequate response to or a history of unacceptable side effects with UDCA were randomly allocated to either oral seladelpar 10 mg daily or placebo for 12 months. The vast majority (93.8%) continued UDCA as standard-of-care background therapy.
The primary endpoint was a biochemical response, which was defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at 12 months.
After 12 months, 61.7% of patients taking seladelpar met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking seladelpar than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the seladelpar group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the seladelpar group compared with 6.5% and 11.4%, respectively, in the placebo group.
“In PBC, we use target endpoints, so the trial was not powered or able to show yet clinical outcomes because the pace of the disease is quite slow. But we believe that the normalization of liver tests and improvement in quality of life will change the disease trajectory over time,” Dr. Hirschfield said.
Significant Reduction in Pruritus
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.
Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.
“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.
The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.
The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
Potential First-Line Treatment?
In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”
“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.
“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.
Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.
“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.
Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.
The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, according to the full results of the RESPONSE phase 3 study.
“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.
The study data are “genuinely exciting...and support the potential for seladelpar to raise the bar in PBC treatment,” Dr. Hirschfield added in a news release.
Seladelpar is being developed by CymaBay Therapeutics, which funded the study.
The results were published online in The New England Journal of Medicine.
Topline data from the study were presented in November at The Liver Meeting 2023: American Association for the Study of Liver Diseases.
‘Unequivocal’ Progress
Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.
Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.
In the RESPONSE study, 193 patients with PBC who had an inadequate response to or a history of unacceptable side effects with UDCA were randomly allocated to either oral seladelpar 10 mg daily or placebo for 12 months. The vast majority (93.8%) continued UDCA as standard-of-care background therapy.
The primary endpoint was a biochemical response, which was defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at 12 months.
After 12 months, 61.7% of patients taking seladelpar met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking seladelpar than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the seladelpar group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the seladelpar group compared with 6.5% and 11.4%, respectively, in the placebo group.
“In PBC, we use target endpoints, so the trial was not powered or able to show yet clinical outcomes because the pace of the disease is quite slow. But we believe that the normalization of liver tests and improvement in quality of life will change the disease trajectory over time,” Dr. Hirschfield said.
Significant Reduction in Pruritus
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.
Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.
“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.
The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.
The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
Potential First-Line Treatment?
In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”
“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.
“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.
Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.
“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.
Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.
The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of di</metaDescription> <articlePDF/> <teaserImage/> <teaser>Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief.</teaser> <title>Seladelpar Could ‘Raise the Bar’ in Primary Biliary Cholangitis Treatment</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> <term>226</term> <term>213</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Seladelpar Could ‘Raise the Bar’ in Primary Biliary Cholangitis Treatment</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC)</span>, according to the full results of the RESPONSE phase 3 study.</p> <p>“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.<br/><br/>The study data are “genuinely exciting...and support the potential for seladelpar to raise the bar in PBC treatment,” Dr. Hirschfield added in a <span class="Hyperlink"><a href="https://www.cymabay.com/investors-media/news-events/press-releases/detail/594/the-new-england-journal-of-medicine-publishes-positive">news release</a></span>.<br/><br/>Seladelpar is being developed by CymaBay Therapeutics, which funded the study.<br/><br/>The results were <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2312100">published online</a></span> in <em>The New England Journal of Medicine</em>.<br/><br/><span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/998611">Topline data from the study</a></span> were presented in November at The Liver Meeting 2023: American Association for the Study of Liver Diseases.<br/><br/></p> <h2>‘Unequivocal’ Progress</h2> <p>Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.</p> <p>Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMe2312745">editorial</a></span>.<br/><br/>In the RESPONSE study, 193 patients with PBC who had an inadequate response to or a history of unacceptable side effects with UDCA were randomly allocated to either oral seladelpar 10 mg daily or placebo for 12 months. The vast majority (93.8%) continued UDCA as standard-of-care background therapy.<br/><br/>The primary endpoint was a biochemical response, which was defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at 12 months.<br/><br/>After 12 months, 61.7% of patients taking seladelpar met the primary endpoint vs 20% of patients taking placebo.<br/><br/>In addition, significantly more patients taking seladelpar than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the seladelpar group vs 4.3% in the placebo group.<br/><br/>At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the seladelpar group compared with 6.5% and 11.4%, respectively, in the placebo group.<br/><br/>“In PBC, we use target endpoints, so the trial was not powered or able to show yet clinical outcomes because the pace of the disease is quite slow. But we believe that the normalization of liver tests and improvement in quality of life will change the disease trajectory over time,” Dr. Hirschfield said.<br/><br/></p> <h2>Significant Reduction in Pruritus</h2> <p>A key secondary endpoint was change in patient-reported pruritus.</p> <p>At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.<br/><br/>Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.<br/><br/>Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.<br/><br/>Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.<br/><br/>“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.<br/><br/>The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.<br/><br/>The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.<br/><br/></p> <h2>Potential First-Line Treatment?</h2> <p>In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported <span class="Hyperlink"><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2306185">ELATIVE trial</a></span> of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”</p> <p>“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.<br/><br/>“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.<br/><br/>Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.<br/><br/>“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.<br/><br/>Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.<br/><br/>The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/seladelpar-could-raise-bar-primary-biliary-cholangitis-2024a10003vi">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
NEJM Study Highlights Resmetirom’s Efficacy in NASH With Liver Fibrosis
published in The New England Journal of Medicine.
Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment.
“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas.
The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively.
A Closer Look at MAESTRO-NASH
Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo).
The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex.
“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote.
The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom.
From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).
More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).
Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion.
Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org.
A version of this article appeared on Medscape.com.
published in The New England Journal of Medicine.
Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment.
“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas.
The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively.
A Closer Look at MAESTRO-NASH
Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo).
The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex.
“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote.
The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom.
From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).
More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).
Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion.
Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org.
A version of this article appeared on Medscape.com.
published in The New England Journal of Medicine.
Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment.
“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas.
The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively.
A Closer Look at MAESTRO-NASH
Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo).
The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex.
“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote.
The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom.
From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).
More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).
Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion.
Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>166871</fileName> <TBEID>0C04E777.SIG</TBEID> <TBUniqueIdentifier>MD_0C04E777</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240209T093406</QCDate> <firstPublished>20240209T100928</firstPublished> <LastPublished>20240209T100928</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240209T100928</CMSDate> <articleSource>FROM THE NEW ENGLAND JOURNAL OF MEDICINE</articleSource> <facebookInfo/> <meetingNumber/> <byline>Becky McCall</byline> <bylineText>BECKY MCCALL</bylineText> <bylineFull>BECKY MCCALL</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achievi</metaDescription> <articlePDF/> <teaserImage>221080</teaserImage> <teaser>Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes.</teaser> <title>NEJM Study Highlights Resmetirom’s Efficacy in NASH With Liver Fibrosis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> <term>213</term> <term>226</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400a061.jpg</altRep> <description role="drol:caption">Dr. Stephen Harrison</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>NEJM Study Highlights Resmetirom’s Efficacy in NASH With Liver Fibrosis</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2038493-overview">nonalcoholic steatohepatitis</a></span> (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial</span> <span class="Hyperlink"><a href="https://doi.org/10.1056/NEJMoa2309000">published</a></span> in <em>The New England Journal of Medicine</em>.</p> <p>Although certain findings from this trial were <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/993575">initially presented</a></span> at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. <br/><br/>[[{"fid":"221080","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Stephen Harrison, medical director of Pinnacle Clinical Research","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Stephen Harrison"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. <br/><br/>The trial uses the earlier nomenclature of NASH and nonalcoholic <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/175472-overview">fatty liver</a></span> disease (NAFLD). An international consensus group <span class="Hyperlink"><a href="https://www.medscape.com/s/viewarticle/994318">has since changed</a></span> these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. <br/><br/></p> <h2>A Closer Look at MAESTRO-NASH</h2> <p>Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. </p> <p>They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. <br/><br/>NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (<em>P</em> < .001 for both doses compared with placebo). <br/><br/>The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. <br/><br/>“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. <br/><br/>The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2500031-overview">cardiovascular risk</a></span> and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2500032-overview">lipids</a></span> and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–<span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2087757-overview">high-density lipoprotein cholesterol</a></span>, <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2074115-overview">triglycerides</a></span>, <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2087335-overview">apolipoprotein B</a></span>, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. <br/><br/>From baseline to week 24, <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/2087735-overview">LDL cholesterol</a></span> levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (<em>P</em> < .001).<br/><br/>More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/928598-overview">Diarrhea</a></span> and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).<br/><br/>Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to <span class="Hyperlink"><a href="https://emedicine.medscape.com/article/185856-overview">cirrhosis</a></span>. Likewise, long-term safety data will become available with the trial’s completion. <br/><br/>Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org.<span class="end"/> </p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/nejm-study-highlights-resmetiroms-efficacy-nash-liver-2024a10002q1">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Meta-Analysis Highlights Litany of MASLD-Associated Complications, Encouraging New Treatment Targets
, based on a large-scale meta-analysis of longitudinal data.
These findings emphasize the multisystemic nature of MASLD, suggesting that broader treatment targets are needed to reduce systemic events and end organ complications, reported lead author Kai En Chan, MBBS, of the National University of Singapore, and colleagues.
“[D]espite the substantial impact of MASLD, with direct medical costs estimated to reach $103 billion in the United States alone, a comprehensive umbrella meta-analysis of the longitudinal complications associated with MASLD has yet to be conducted,” the investigators wrote in Clinical Gastroenterology and Hepatology, noting that key outcomes associated with sex and disease severity have yet to be elucidated. “A comprehensive understanding of the spectrum of clinical complications associated with MASLD is thus crucial in developing effective disease management strategies and optimizing the allocation of limited healthcare resources.”
To this end, the investigators analyzed data from 129 studies reporting longitudinal risks of clinical outcomes among adults with MASLD. Assessed complications spanned a broad array of organ systems and pathologies. Cardiovascular and oncologic conditions predominated, while chronic kidney disease, liver-related outcomes, gallstone formation, dementia, and reflux esophagitis were also considered.
The analysis revealed significant associations between MASLD and — in ascending level of risk — chronic kidney disease (hazard ratio [HR], 1.38), cardiovascular diseases (HR, 1.43), cancer (HR, 1.54), prediabetes (HR, 1.69), hypertension (HR, 1.75), diabetes (HR, 2.56), and metabolic syndrome (HR, 2.57).
Across cardiovascular diseases, MASLD raised risk of hypertension the most, by 75%. Among cancer types, MASLD increased risk of hepatocellular carcinoma to the greatest degree, by more than fourfold.
No significant sex-specific differences in MASLD-associated risk were detected for cancer, chronic kidney disease, diabetes, or cardiovascular disease, although the investigators urged a cautious interpretation of these findings, since relevant data were scarce.
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the investigators wrote.
They also suggested that the link between MASLD and cancer deserves particular attention.
“Although the mechanism by which MASLD gives rise to cardiovascular disease and diabetes has been thoroughly researched, the pathophysiology of MASLD leading to extrahepatic carcinogenesis is less well understood and has been postulated to be linked to chronic inflammation and dysregulation of the gut microbiome in MASLD,” they wrote.
Lastly, considering the multiprong association between MASLD and so many complications, the investigators recommended broader clinical metrics for measuring outcomes in patients with MASLD.
“With the synergistic increases of metabolic diseases globally, treatment targets should in turn act beyond the resolution of fibrosis but also to reduce systemic end organ complications,” they concluded.The investigators disclosed relationships with AbbVie, Echosens, Gilead Sciences, and others.
In a massive meta-analysis of 129 studies that included over 6 million participants, Chan and colleagues evaluated the associations of MASLD with incident hepatic and extrahepatic outcomes. They report numerous associations for MASLD with metabolic, cardiovascular, and renal events as well as with gastrointestinal, hepatobiliary, and other types of cancers.
[[{"fid":"300210","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"}},"attributes":{"alt":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","class":"media-element file-medstat-image-flush-right","data-delta":"1"}}]]Some of their findings are congruent with prior research establishing the independent association of MASLD with future development of cardiovascular and renal disease, diabetes, and hepatocellular carcinoma. It is, however, unclear if the additional MASLD associations they report, such as with nonliver malignancies, would persist if adjustment for relevant covariates affecting these outcomes were performed. While the large number of participants from different study populations included in the analysis can be a strength, the resulting considerable heterogeneity calls for caution in interpreting some of the associations and their magnitudes.
The unimpeded pace of the obesity pandemic remains a steady driver of the rise in the burden of metabolic syndrome and its components, including MASLD. Thus, approaches to tackle the rising burden of metabolic diseases including MASLD should start with the root driver, obesity. It is also imperative to consider addressing the cardiometabolic milieu in any approach designed to specifically target MASLD/MASH. Lifestyle modifications that include weight loss, smoking cessation, and avoidance of alcohol use may help reduce risks of cardiovascular disease and cancer, the leading causes of death in patients with MASLD. Anticipated pharmacologic therapies for MASH should not only improve liver endpoints but also have a beneficial or, at minimum, neutral extrahepatic effects on coexisting cardiometabolic conditions.
Samer Gawrieh, MD, is professor of clinical medicine in the Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis, where he serves as the Director of Hepatology Research and Clinical Fellowship Program. He receives funding for the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Alcohol Abuse and Alcoholism, and research grant support from Zydus and Viking, and serves on safety committees with TransMedics, Pfizer and Spruce.
In a massive meta-analysis of 129 studies that included over 6 million participants, Chan and colleagues evaluated the associations of MASLD with incident hepatic and extrahepatic outcomes. They report numerous associations for MASLD with metabolic, cardiovascular, and renal events as well as with gastrointestinal, hepatobiliary, and other types of cancers.
[[{"fid":"300210","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"}},"attributes":{"alt":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","class":"media-element file-medstat-image-flush-right","data-delta":"1"}}]]Some of their findings are congruent with prior research establishing the independent association of MASLD with future development of cardiovascular and renal disease, diabetes, and hepatocellular carcinoma. It is, however, unclear if the additional MASLD associations they report, such as with nonliver malignancies, would persist if adjustment for relevant covariates affecting these outcomes were performed. While the large number of participants from different study populations included in the analysis can be a strength, the resulting considerable heterogeneity calls for caution in interpreting some of the associations and their magnitudes.
The unimpeded pace of the obesity pandemic remains a steady driver of the rise in the burden of metabolic syndrome and its components, including MASLD. Thus, approaches to tackle the rising burden of metabolic diseases including MASLD should start with the root driver, obesity. It is also imperative to consider addressing the cardiometabolic milieu in any approach designed to specifically target MASLD/MASH. Lifestyle modifications that include weight loss, smoking cessation, and avoidance of alcohol use may help reduce risks of cardiovascular disease and cancer, the leading causes of death in patients with MASLD. Anticipated pharmacologic therapies for MASH should not only improve liver endpoints but also have a beneficial or, at minimum, neutral extrahepatic effects on coexisting cardiometabolic conditions.
Samer Gawrieh, MD, is professor of clinical medicine in the Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis, where he serves as the Director of Hepatology Research and Clinical Fellowship Program. He receives funding for the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Alcohol Abuse and Alcoholism, and research grant support from Zydus and Viking, and serves on safety committees with TransMedics, Pfizer and Spruce.
In a massive meta-analysis of 129 studies that included over 6 million participants, Chan and colleagues evaluated the associations of MASLD with incident hepatic and extrahepatic outcomes. They report numerous associations for MASLD with metabolic, cardiovascular, and renal events as well as with gastrointestinal, hepatobiliary, and other types of cancers.
[[{"fid":"300210","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"}},"attributes":{"alt":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","class":"media-element file-medstat-image-flush-right","data-delta":"1"}}]]Some of their findings are congruent with prior research establishing the independent association of MASLD with future development of cardiovascular and renal disease, diabetes, and hepatocellular carcinoma. It is, however, unclear if the additional MASLD associations they report, such as with nonliver malignancies, would persist if adjustment for relevant covariates affecting these outcomes were performed. While the large number of participants from different study populations included in the analysis can be a strength, the resulting considerable heterogeneity calls for caution in interpreting some of the associations and their magnitudes.
The unimpeded pace of the obesity pandemic remains a steady driver of the rise in the burden of metabolic syndrome and its components, including MASLD. Thus, approaches to tackle the rising burden of metabolic diseases including MASLD should start with the root driver, obesity. It is also imperative to consider addressing the cardiometabolic milieu in any approach designed to specifically target MASLD/MASH. Lifestyle modifications that include weight loss, smoking cessation, and avoidance of alcohol use may help reduce risks of cardiovascular disease and cancer, the leading causes of death in patients with MASLD. Anticipated pharmacologic therapies for MASH should not only improve liver endpoints but also have a beneficial or, at minimum, neutral extrahepatic effects on coexisting cardiometabolic conditions.
Samer Gawrieh, MD, is professor of clinical medicine in the Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis, where he serves as the Director of Hepatology Research and Clinical Fellowship Program. He receives funding for the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Alcohol Abuse and Alcoholism, and research grant support from Zydus and Viking, and serves on safety committees with TransMedics, Pfizer and Spruce.
, based on a large-scale meta-analysis of longitudinal data.
These findings emphasize the multisystemic nature of MASLD, suggesting that broader treatment targets are needed to reduce systemic events and end organ complications, reported lead author Kai En Chan, MBBS, of the National University of Singapore, and colleagues.
“[D]espite the substantial impact of MASLD, with direct medical costs estimated to reach $103 billion in the United States alone, a comprehensive umbrella meta-analysis of the longitudinal complications associated with MASLD has yet to be conducted,” the investigators wrote in Clinical Gastroenterology and Hepatology, noting that key outcomes associated with sex and disease severity have yet to be elucidated. “A comprehensive understanding of the spectrum of clinical complications associated with MASLD is thus crucial in developing effective disease management strategies and optimizing the allocation of limited healthcare resources.”
To this end, the investigators analyzed data from 129 studies reporting longitudinal risks of clinical outcomes among adults with MASLD. Assessed complications spanned a broad array of organ systems and pathologies. Cardiovascular and oncologic conditions predominated, while chronic kidney disease, liver-related outcomes, gallstone formation, dementia, and reflux esophagitis were also considered.
The analysis revealed significant associations between MASLD and — in ascending level of risk — chronic kidney disease (hazard ratio [HR], 1.38), cardiovascular diseases (HR, 1.43), cancer (HR, 1.54), prediabetes (HR, 1.69), hypertension (HR, 1.75), diabetes (HR, 2.56), and metabolic syndrome (HR, 2.57).
Across cardiovascular diseases, MASLD raised risk of hypertension the most, by 75%. Among cancer types, MASLD increased risk of hepatocellular carcinoma to the greatest degree, by more than fourfold.
No significant sex-specific differences in MASLD-associated risk were detected for cancer, chronic kidney disease, diabetes, or cardiovascular disease, although the investigators urged a cautious interpretation of these findings, since relevant data were scarce.
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the investigators wrote.
They also suggested that the link between MASLD and cancer deserves particular attention.
“Although the mechanism by which MASLD gives rise to cardiovascular disease and diabetes has been thoroughly researched, the pathophysiology of MASLD leading to extrahepatic carcinogenesis is less well understood and has been postulated to be linked to chronic inflammation and dysregulation of the gut microbiome in MASLD,” they wrote.
Lastly, considering the multiprong association between MASLD and so many complications, the investigators recommended broader clinical metrics for measuring outcomes in patients with MASLD.
“With the synergistic increases of metabolic diseases globally, treatment targets should in turn act beyond the resolution of fibrosis but also to reduce systemic end organ complications,” they concluded.The investigators disclosed relationships with AbbVie, Echosens, Gilead Sciences, and others.
, based on a large-scale meta-analysis of longitudinal data.
These findings emphasize the multisystemic nature of MASLD, suggesting that broader treatment targets are needed to reduce systemic events and end organ complications, reported lead author Kai En Chan, MBBS, of the National University of Singapore, and colleagues.
“[D]espite the substantial impact of MASLD, with direct medical costs estimated to reach $103 billion in the United States alone, a comprehensive umbrella meta-analysis of the longitudinal complications associated with MASLD has yet to be conducted,” the investigators wrote in Clinical Gastroenterology and Hepatology, noting that key outcomes associated with sex and disease severity have yet to be elucidated. “A comprehensive understanding of the spectrum of clinical complications associated with MASLD is thus crucial in developing effective disease management strategies and optimizing the allocation of limited healthcare resources.”
To this end, the investigators analyzed data from 129 studies reporting longitudinal risks of clinical outcomes among adults with MASLD. Assessed complications spanned a broad array of organ systems and pathologies. Cardiovascular and oncologic conditions predominated, while chronic kidney disease, liver-related outcomes, gallstone formation, dementia, and reflux esophagitis were also considered.
The analysis revealed significant associations between MASLD and — in ascending level of risk — chronic kidney disease (hazard ratio [HR], 1.38), cardiovascular diseases (HR, 1.43), cancer (HR, 1.54), prediabetes (HR, 1.69), hypertension (HR, 1.75), diabetes (HR, 2.56), and metabolic syndrome (HR, 2.57).
Across cardiovascular diseases, MASLD raised risk of hypertension the most, by 75%. Among cancer types, MASLD increased risk of hepatocellular carcinoma to the greatest degree, by more than fourfold.
No significant sex-specific differences in MASLD-associated risk were detected for cancer, chronic kidney disease, diabetes, or cardiovascular disease, although the investigators urged a cautious interpretation of these findings, since relevant data were scarce.
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the investigators wrote.
They also suggested that the link between MASLD and cancer deserves particular attention.
“Although the mechanism by which MASLD gives rise to cardiovascular disease and diabetes has been thoroughly researched, the pathophysiology of MASLD leading to extrahepatic carcinogenesis is less well understood and has been postulated to be linked to chronic inflammation and dysregulation of the gut microbiome in MASLD,” they wrote.
Lastly, considering the multiprong association between MASLD and so many complications, the investigators recommended broader clinical metrics for measuring outcomes in patients with MASLD.
“With the synergistic increases of metabolic diseases globally, treatment targets should in turn act beyond the resolution of fibrosis but also to reduce systemic end organ complications,” they concluded.The investigators disclosed relationships with AbbVie, Echosens, Gilead Sciences, and others.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>166678</fileName> <TBEID>0C04E283.SIG</TBEID> <TBUniqueIdentifier>MD_0C04E283</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>CGH_Chan_MASLD</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240207T105131</QCDate> <firstPublished>20240207T105259</firstPublished> <LastPublished>20240207T105259</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240207T105259</CMSDate> <articleSource>FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY</articleSource> <facebookInfo/> <meetingNumber/> <byline>Will Pass</byline> <bylineText>WILL PASS</bylineText> <bylineFull>WILL PASS</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with a host of negative clinical outcomes across cardiovascular, metabolic, and o</metaDescription> <articlePDF/> <teaserImage>300210</teaserImage> <teaser>The findings emphasize the multisystemic nature of MASLD, suggesting that broader treatment targets are needed.</teaser> <title>Meta-Analysis Highlights Litany of MASLD-Associated Complications, Encouraging New Treatment Targets</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> </publications> <sections> <term canonical="true">69</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012633.jpg</altRep> <description role="drol:caption">Dr. Samer Gawrieh</description> <description role="drol:credit">Indiana University School of Medicine</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Meta-Analysis Highlights Litany of MASLD-Associated Complications, Encouraging New Treatment Targets</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with a host of negative clinical outcomes across cardiovascular, metabolic, and oncologic domains</span>, based on a large-scale meta-analysis of longitudinal data. </p> <p>These findings emphasize the multisystemic nature of MASLD, suggesting that broader treatment targets are needed to reduce systemic events and end organ complications, reported lead author <a href="https://www.linkedin.com/in/chan-kai-en-3455b1208/?originalSubdomain=sg">Kai En Chan, MBBS</a>, of the National University of Singapore, and colleagues.<br/><br/>“[D]espite the substantial impact of MASLD, with direct medical costs estimated to reach $103 billion in the United States alone, a comprehensive umbrella meta-analysis of the longitudinal complications associated with MASLD has yet to be conducted,” the <span class="Hyperlink"><a href="https://www.cghjournal.org/article/S1542-3565(23)00754-1/fulltext">investigators wrote</a></span> in <em>Clinical Gastroenterology and Hepatology</em>, noting that key outcomes associated with sex and disease severity have yet to be elucidated. “A comprehensive understanding of the spectrum of clinical complications associated with MASLD is thus crucial in developing effective disease management strategies and optimizing the allocation of limited healthcare resources.”<br/><br/>To this end, the investigators analyzed data from 129 studies reporting longitudinal risks of clinical outcomes among adults with MASLD. Assessed complications spanned a broad array of organ systems and pathologies. Cardiovascular and oncologic conditions predominated, while chronic kidney disease, liver-related outcomes, gallstone formation, dementia, and reflux esophagitis were also considered.<br/><br/>The analysis revealed significant associations between MASLD and — in ascending level of risk — chronic kidney disease (hazard ratio [HR], 1.38), cardiovascular diseases (HR, 1.43), cancer (HR, 1.54), prediabetes (HR, 1.69), hypertension (HR, 1.75), diabetes (HR, 2.56), and metabolic syndrome (HR, 2.57).<br/><br/>Across cardiovascular diseases, MASLD raised risk of hypertension the most, by 75%. Among cancer types, MASLD increased risk of hepatocellular carcinoma to the greatest degree, by more than fourfold. <br/><br/>No significant sex-specific differences in MASLD-associated risk were detected for cancer, chronic kidney disease, diabetes, or cardiovascular disease, although the investigators urged a cautious interpretation of these findings, since relevant data were scarce.<br/><br/>“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the investigators wrote.<br/><br/>They also suggested that the link between MASLD and cancer deserves particular attention.<br/><br/> “Although the mechanism by which MASLD gives rise to cardiovascular disease and diabetes has been thoroughly researched, the pathophysiology of MASLD leading to extrahepatic carcinogenesis is less well understood and has been postulated to be linked to chronic inflammation and dysregulation of the gut microbiome in MASLD,” they wrote.<br/><br/>Lastly, considering the multiprong association between MASLD and so many complications, the investigators recommended broader clinical metrics for measuring outcomes in patients with MASLD.<br/><br/>“With the synergistic increases of metabolic diseases globally, treatment targets should in turn act beyond the resolution of fibrosis but also to reduce systemic end organ complications,” they concluded.The investigators disclosed relationships with AbbVie, Echosens, Gilead Sciences, and others.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>views</itemRole> <itemClass>text</itemClass> <title>Start With the Root Driver — Obesity</title> <deck/> </itemMeta> <itemContent> <p>In a massive meta-analysis of 129 studies that included over 6 million participants, Chan and colleagues evaluated the associations of MASLD with incident hepatic and extrahepatic outcomes. They report numerous associations for MASLD with metabolic, cardiovascular, and renal events as well as with gastrointestinal, hepatobiliary, and other types of cancers. </p> <p>[[{"fid":"300210","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Samer Gawrieh, Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis. Director of Hepatology Research and Clinical Fellowship Program","field_file_image_credit[und][0][value]":"Indiana University School of Medicine","field_file_image_caption[und][0][value]":"Dr. Samer Gawrieh"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]Some of their findings are congruent with prior research establishing the independent association of MASLD with future development of cardiovascular and renal disease, diabetes, and hepatocellular carcinoma. It is, however, unclear if the additional MASLD associations they report, such as with nonliver malignancies, would persist if adjustment for relevant covariates affecting these outcomes were performed. While the large number of participants from different study populations included in the analysis can be a strength, the resulting considerable heterogeneity calls for caution in interpreting some of the associations and their magnitudes.<br/><br/>The unimpeded pace of the obesity pandemic remains a steady driver of the rise in the burden of metabolic syndrome and its components, including MASLD. Thus, approaches to tackle the rising burden of metabolic diseases including MASLD should start with the root driver, obesity. It is also imperative to consider addressing the cardiometabolic milieu in any approach designed to specifically target MASLD/MASH. Lifestyle modifications that include weight loss, smoking cessation, and avoidance of alcohol use may help reduce risks of cardiovascular disease and cancer, the leading causes of death in patients with MASLD. Anticipated pharmacologic therapies for MASH should not only improve liver endpoints but also have a beneficial or, at minimum, neutral extrahepatic effects on coexisting cardiometabolic conditions.<br/><br/></p> <p><em> <em>Samer Gawrieh, MD, is professor of clinical medicine in the Division of Gastroenterology and Hepatology at Indiana University School of Medicine, Indianapolis, where he serves as the Director of Hepatology Research and Clinical Fellowship Program. He receives funding for the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Alcohol Abuse and Alcoholism, and research grant support from Zydus and Viking, and serves on safety committees with TransMedics, Pfizer and Spruce.</em> </em></p> </itemContent> </newsItem> </itemSet></root>
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Dueling Gut Bacteria Impact Chronic HBV Progression
, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
[[{"fid":"300195","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"}},"attributes":{"alt":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","class":"media-element file-medstat-image-flush-left","data-delta":"1"}}]]In the latest issue of Cellular and Molecular Gastroenterology and Hepatology, Chua et al. shed new light on the direct involvement of gut microbiota in regulating the progression of CHB. Specifically, using fecal samples from CHB patients and a hepatitis B virus (HBV) mouse model, the research team demonstrates that the gut bacterium Ruminococcus gnavus promotes IT and HBV persistence, while Akkermansia muciniphila favors the transition from the IT to IA phase and HBV clearance. Furthermore, R. gnavus modulates bile acid metabolism to facilitate HBV replication, while A. muciniphila removes cholesterol and secretes metabolites that inhibit the growth and function of R. gnavus.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
[[{"fid":"300195","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"}},"attributes":{"alt":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","class":"media-element file-medstat-image-flush-left","data-delta":"1"}}]]In the latest issue of Cellular and Molecular Gastroenterology and Hepatology, Chua et al. shed new light on the direct involvement of gut microbiota in regulating the progression of CHB. Specifically, using fecal samples from CHB patients and a hepatitis B virus (HBV) mouse model, the research team demonstrates that the gut bacterium Ruminococcus gnavus promotes IT and HBV persistence, while Akkermansia muciniphila favors the transition from the IT to IA phase and HBV clearance. Furthermore, R. gnavus modulates bile acid metabolism to facilitate HBV replication, while A. muciniphila removes cholesterol and secretes metabolites that inhibit the growth and function of R. gnavus.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.
[[{"fid":"300195","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"}},"attributes":{"alt":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","class":"media-element file-medstat-image-flush-left","data-delta":"1"}}]]In the latest issue of Cellular and Molecular Gastroenterology and Hepatology, Chua et al. shed new light on the direct involvement of gut microbiota in regulating the progression of CHB. Specifically, using fecal samples from CHB patients and a hepatitis B virus (HBV) mouse model, the research team demonstrates that the gut bacterium Ruminococcus gnavus promotes IT and HBV persistence, while Akkermansia muciniphila favors the transition from the IT to IA phase and HBV clearance. Furthermore, R. gnavus modulates bile acid metabolism to facilitate HBV replication, while A. muciniphila removes cholesterol and secretes metabolites that inhibit the growth and function of R. gnavus.
This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential A. muciniphila–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of A. muciniphila supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.
Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.
, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
, according to investigators.
While Ruminococcus gnavus promotes immune tolerance and therefore HBV persistence, Akkermansia muciniphila stimulates the immune system, promoting viral clearance, reported lead author Huey-Huey Chua, MD, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.
These findings could lead to new therapeutic strategies, such as administration of the secretory products of A. muciniphila, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.
“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”
They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection.
R. gnavus was the most abundant species among IT patients, whereas A. muciniphila was most abundant among patients in the IA phase. Higher levels of A. muciniphila were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.
Further experiments with mouse models revealed that R. gnavus modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, A. muciniphila removes cholesterol and secretes metabolites that inhibit growth and function of R. gnavus.
“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.
They went on to describe several therapeutic strategies worth further investigation.
“A key step to promote switching from the IT to IA phase is to lessen the richness of R. gnavus and bile acid bioconversion from cholesterol,” they wrote. The secretory products of A. muciniphila that successfully ameliorate the burden of R. gnavus outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of A. muciniphila while inhibiting the detrimental effects of R. gnavus may have translational value for CHB.”
The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>166675</fileName> <TBEID>0C04E21D.SIG</TBEID> <TBUniqueIdentifier>MD_0C04E21D</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>CMGH_Chua_HBV</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240206T100055</QCDate> <firstPublished>20240206T100809</firstPublished> <LastPublished>20240206T100809</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240206T100809</CMSDate> <articleSource>FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY</articleSource> <facebookInfo/> <meetingNumber/> <byline>Will Pass</byline> <bylineText>WILL PASS</bylineText> <bylineFull>WILL PASS</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Two species of gut bacteria modulate the immune system and even the survival of one another to impact the progression of chronic hepatitis B (CHB)</metaDescription> <articlePDF/> <teaserImage>300195</teaserImage> <teaser>These findings could lead to new therapeutic strategies, researchers say.</teaser> <title>Dueling Gut Bacteria Impact Chronic HBV Progression</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>gih</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">17</term> </publications> <sections> <term canonical="true">69</term> <term>39313</term> </sections> <topics> <term canonical="true">346</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2401262a.jpg</altRep> <description role="drol:caption">Dr. Dawu Zeng</description> <description role="drol:credit">Dr. Zeng</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Dueling Gut Bacteria Impact Chronic HBV Progression</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">Two species of gut bacteria modulate the immune system and even the survival of one another to impact the progression of chronic hepatitis B (CHB)</span>, according to investigators.</p> <p>While <em>Ruminococcus gnavus</em> promotes immune tolerance and therefore HBV persistence, <em>Akkermansia muciniphila</em> stimulates the immune system, promoting viral clearance, reported lead author <a href="https://www.researchgate.net/scientific-contributions/Huey-Huey-Chua-38848966">Huey-Huey Chua, MD</a>, of the National Taiwan University College of Medicine and Children’s Hospital, Taipei, and colleagues.<br/><br/>These findings could lead to new therapeutic strategies, such as administration of the secretory products of <em>A. muciniphila</em>, or provision of probiotics and prebiotics that tip the balance toward this more beneficial bacterium, <span class="Hyperlink"><a href="https://www.cmghjournal.org/article/S2352-345X(23)00216-3/fulltext">the investigators wrote</a></span> in <em>Cellular and Molecular Gastroenterology and Hepatology</em>.<br/><br/>Their study, which included data from both human patients and mouse models of CHB, was grounded in prior research showing a link between gut microbiota and the age-dependence of HBV immunity.<br/><br/>“Sterilization of the gut microbiota using antibiotics prevents adult mice from rapidly clearing HBV and restores the tolerance phenotype, implying that the gut microbiota may transmit signals to break liver tolerance and evoke rapid HBV clearance,” Dr. Chua and colleagues wrote. “We hypothesized that the wax and wane of gut microbiota signatures may determine the progression of CHB. We aimed to delineate what the pivotal bacteria are and how they manipulate the progression of CHB.”<br/><br/>They began by analyzing fecal samples from 102 patients with CHB either in the immune-tolerant (IT) or immune-active (IA) phase of infection. <br/><br/><em>R. gnavus</em> was the most abundant species among IT patients, whereas <em>A. muciniphila</em> was most abundant among patients in the IA phase. Higher levels of <em>A. muciniphila</em> were also associated with early hepatitis B e-antigen (HBeAG) loss, HBeAG seroconversion, and flares of aminotransferase. A mouse model echoed these findings.<br/><br/>Further experiments with mouse models revealed that <em>R. gnavus</em> modulates bile acids to promote HBV persistence and prolongation of the IT course. In opposition, <em>A. muciniphila</em> removes cholesterol and secretes metabolites that inhibit growth and function of <em>R. gnavus</em>.<br/><br/>“These novel findings will certainly confer a groundbreaking impact on the future therapy of CHB,” Dr. Chua and colleagues wrote.<br/><br/>They went on to describe several therapeutic strategies worth further investigation.<br/><br/>“A key step to promote switching from the IT to IA phase is to lessen the richness of <em>R. gnavus</em> and bile acid bioconversion from cholesterol,” they wrote. The secretory products of <em>A. muciniphila</em> that successfully ameliorate the burden of <em>R. gnavus</em> outgrowth can be provided as useful means to induce anti-HBV efficacy. Also, the development of targeted probiotics or prebiotics that can modulate the gut microbiota composition to favor the beneficial effects of <em>A. muciniphila</em> while inhibiting the detrimental effects of <em>R. gnavus</em> may have translational value for CHB.”<br/><br/>The study was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan and the Center of Precision Medicine from Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. The investigators disclosed no conflicts of interest.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>views</itemRole> <itemClass>text</itemClass> <title>‘Important advancement’ offers insights for potential therapies</title> <deck/> </itemMeta> <itemContent> <p>Clinical observations have long indicated that chronic hepatitis B (CHB) patients with a prolonged immune-tolerant (IT) phase are at a higher risk of liver diseases, while those with an early transition to the immune-active (IA) phase are associated with a better clinical outcome. However, the underlying mechanisms remain unclear.</p> <p>[[{"fid":"300195","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Dawu Zeng, Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China","field_file_image_credit[und][0][value]":"Dr. Zeng","field_file_image_caption[und][0][value]":"Dr. Dawu Zeng"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]In the latest issue of <em>Cellular and Molecular Gastroenterology and Hepatology</em>, Chua et al. shed new light on the direct involvement of gut microbiota in regulating the progression of CHB. Specifically, using fecal samples from CHB patients and a hepatitis B virus (HBV) mouse model, the research team demonstrates that the gut bacterium <em>Ruminococcus gnavus</em> promotes IT and HBV persistence, while <em>Akkermansia muciniphila</em> favors the transition from the IT to IA phase and HBV clearance. Furthermore, <em>R. gnavus</em> modulates bile acid metabolism to facilitate HBV replication, while <em>A. muciniphila</em> removes cholesterol and secretes metabolites that inhibit the growth and function of <em>R. gnavus</em>.<br/><br/>This study merits attention as it marks an important advancement in our understanding of how gut microbiota affects the immune response and, in turn, the progression of CHB, offering insights for potential <em>A. muciniphila</em>–based therapies. Nonetheless, the research is still in its infancy, and further studies, including longitudinal analysis to determine gut microbiota changes from IT to IA, are required. The prospect of <em>A. muciniphila</em> supplementation could be beneficial for CHB patients, warranting clinical trials. Continued research could lead to improved management and prevention of liver diseases in this patient population with CHB.<br/><br/></p> <p><em> <em>Qirong Jiang, MD, and Dawu Zeng, MD, are based in the Hepatology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. They report no conflicts of interest.</em> </em></p> </itemContent> </newsItem> </itemSet></root>
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
