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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.
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.
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.
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.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Iron Overload in Non-HFE Liver Disease: Not all Iron is Ready to Strike
Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.
The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.
Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.
Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.
The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.
Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.
Pathological iron overload with end-organ damage in hemochromatosis occurs in individuals who are homozygous for the major mutation C282Y. Phenotypic hemochromatosis occurs much less frequently in compound heterozygotes with one C282Y mutation and one H63D mutation. Iron overload can be confirmed by magnetic resonance imaging, which shows a loss of signal intensity in affected tissues and avoids the need for liver biopsy.
The serum ferritin level, an acute phase reactant, may be elevated for reasons other than iron overload, including infection and malignancy; in such cases, the iron saturation is usually normal. In patients with liver disease, iron overload is not restricted to patients with genetic hemochromatosis. In nonalcoholic fatty liver disease (NAFLD), up to one-third of patients have an elevated iron saturation (> 45%) and an elevated serum ferritin level. Iron accumulation in NAFLD can occur in hepatocytes, the reticuloendothelial system, or both. Deposition of iron in the reticuloendothelial system has been implicated in more severe liver disease (steatohepatitis and fibrosis) in NAFLD. Hepatic iron accumulation is also frequent in alcohol-associated liver disease. In chronic hepatitis B and C, accumulation of hepatic iron is also recognized.
Dr. Martin is chief of the division of digestive health and liver diseases at the Miller School of Medicine, University of Miami, where he is the Mandel Chair of Gastroenterology. Dr. Friedman is the Anton R. Fried, MD, Chair of the department of medicine at Newton-Wellesley Hospital in Newton, Massachusetts, and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University School of Medicine, all in Boston. The authors disclosed no conflicts. Previously published in Gastro Hep Advances. 2023 Oct 12. doi: 10.1016/j.gastha.2023.10.004.
New Guideline Offers Recommendations for Alcohol-Associated Liver Disease
according to a new clinical guideline from the American College of Gastroenterology.
In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.
Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.
“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”
The guideline was published in the January issue of the American Journal of Gastroenterology.
Updating ALD Recommendations
With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.
In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.
To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.
Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.
“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”
In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.
Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.
“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
Policy Implications
Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.
“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”
Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.
“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.
Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.
“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”
The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.
A version of this article appeared on Medscape.com.
according to a new clinical guideline from the American College of Gastroenterology.
In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.
Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.
“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”
The guideline was published in the January issue of the American Journal of Gastroenterology.
Updating ALD Recommendations
With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.
In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.
To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.
Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.
“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”
In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.
Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.
“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
Policy Implications
Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.
“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”
Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.
“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.
Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.
“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”
The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.
A version of this article appeared on Medscape.com.
according to a new clinical guideline from the American College of Gastroenterology.
In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.
Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.
“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”
The guideline was published in the January issue of the American Journal of Gastroenterology.
Updating ALD Recommendations
With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.
In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.
To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.
Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.
“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”
In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.
Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.
“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
Policy Implications
Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.
“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”
Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.
“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.
Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.
“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”
The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.
A version of this article appeared on Medscape.com.
The Breakthrough Drug Whose Full Promise Remains Unrealized
Celebrating a Decade of Sofosbuvir for Hepatitis C
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.
Celebrating a Decade of Sofosbuvir for Hepatitis C
Celebrating a Decade of Sofosbuvir for Hepatitis C
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.
Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.
Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.
The Sofosbuvir Revolution Begins
The Liver Meeting held in 2013 changed everything.
Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.
However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.
This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.
On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.
Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.
Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.
Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.
This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.
This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.
Progress, but Far From Reaching Targets
Fast-forward to 2023.
Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.
In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.
Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.
The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.
Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).
In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.
Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.
As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:
- A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
- HCV antibody testing with reflex to PCR should be used as the screening test.
- Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
- Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.
Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.
Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article appeared on Medscape.com.
February 2024 – ICYMI
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
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. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
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. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
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. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Rebranding NAFLD: Correcting ‘Flawed’ Conventions
Nonalcoholic fatty liver disease (NAFLD) should now be referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), according to a recent commentary by leading hepatologists.
This update, which was determined by a panel of 236 panelists from 56 countries, is part of a broader effort to rebrand “fatty liver disease” as “steatotic liver disease” (SLD), reported lead author Alina M. Allen, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
Writing in Gastroenterology, they described a range of reasons for the nomenclature changes, from the need for better characterization of disease subtypes, to the concern that the term “fatty” may be perceived as stigmatizing by some patients.
“The scientific community and stakeholder organizations associated with liver diseases determined there was a need for new terminology to cover liver disease related to alcohol alone, metabolic risk factors (until recently termed NAFLD/nonalcoholic steatohepatitis [NASH]) alone, the combination of alcohol and metabolic risk factors, and hepatic steatosis due to other specific etiologies,” the authors wrote.
Naming conventions in this area have been flawed since inception, Dr. Allen and colleagues wrote, noting that “nonalcoholic” is exclusionary rather than descriptive, and is particularly misplaced in the pediatric setting. These shortcomings could explain why the term “NASH” took more than a decade to enter common usage, they suggested, and why the present effort is not the first of its kind.
“There have been several movements to change the nomenclature [of NAFLD], including most recently to ‘metabolic dysfunction–associated fatty liver disease’ (MAFLD), a term that received limited traction,” the authors wrote.
Still, a change is needed, they added, as metabolic dysfunction is becoming increasingly common on a global scale, driving up rates of liver disease. Furthermore, in some patients, alcohol consumption and metabolic factors concurrently drive steatosis, suggesting an intermediate condition between alcohol-related liver disease (ALD) and NAFLD that is indescribable via current naming conventions.
SLD (determined by imaging or biopsy) now comprises five disease subtypes that can be determined via an algorithm provided in the present publication.
If at least one metabolic criterion is present, but no other causes of steatosis, then that patient has MASLD. The three other metabolic subtypes include MetALD (2-3 drinks per day for women and 3-4 drinks per day for men), ALD (more than 3 drinks per day for women and more than 4 drinks per day for men), and monogenic miscellaneous drug-induced liver injury (DILI).
Patients without metabolic criteria can also be classified with monogenic miscellaneous DILI with no caveat, whereas patients with metabolic criteria need only consume 2 or 3 drinks per day for women or 3-4 drinks per day for men, respectively, to be diagnosed with ALD.
Finally, patients with no metabolic criteria or other cause of steatosis should be characterized by cryptogenic SLD.
“While renaming and redefining the disease was needed, the implementation is not without challenges,” Dr. Allen and colleagues wrote. “A more complex classification may add confusion in the mind of nonhepatology providers when awareness and understanding of the implications of SLD are already suboptimal.”
Still, they predicted that the new naming system could lead to several positive outcomes, including improved SLD screening among individuals with metabolic risk factors, more accurate phenotyping of patients with moderate alcohol consumption, increased disease awareness in nonhepatology practices, and improved multidisciplinary collaboration.
Only time will tell whether these benefits come to fruition, Dr. Allen and colleagues noted, before closing with a quote: “In the words of Jean Piaget, the developmental psychologist of the 20th century, who coincidentally died the year the term NASH was coined, ‘Scientific knowledge is in perpetual evolution; it finds itself changed from one day to the next.’”
The authors disclosed no conflicts of interest.
Nonalcoholic fatty liver disease (NAFLD) should now be referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), according to a recent commentary by leading hepatologists.
This update, which was determined by a panel of 236 panelists from 56 countries, is part of a broader effort to rebrand “fatty liver disease” as “steatotic liver disease” (SLD), reported lead author Alina M. Allen, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
Writing in Gastroenterology, they described a range of reasons for the nomenclature changes, from the need for better characterization of disease subtypes, to the concern that the term “fatty” may be perceived as stigmatizing by some patients.
“The scientific community and stakeholder organizations associated with liver diseases determined there was a need for new terminology to cover liver disease related to alcohol alone, metabolic risk factors (until recently termed NAFLD/nonalcoholic steatohepatitis [NASH]) alone, the combination of alcohol and metabolic risk factors, and hepatic steatosis due to other specific etiologies,” the authors wrote.
Naming conventions in this area have been flawed since inception, Dr. Allen and colleagues wrote, noting that “nonalcoholic” is exclusionary rather than descriptive, and is particularly misplaced in the pediatric setting. These shortcomings could explain why the term “NASH” took more than a decade to enter common usage, they suggested, and why the present effort is not the first of its kind.
“There have been several movements to change the nomenclature [of NAFLD], including most recently to ‘metabolic dysfunction–associated fatty liver disease’ (MAFLD), a term that received limited traction,” the authors wrote.
Still, a change is needed, they added, as metabolic dysfunction is becoming increasingly common on a global scale, driving up rates of liver disease. Furthermore, in some patients, alcohol consumption and metabolic factors concurrently drive steatosis, suggesting an intermediate condition between alcohol-related liver disease (ALD) and NAFLD that is indescribable via current naming conventions.
SLD (determined by imaging or biopsy) now comprises five disease subtypes that can be determined via an algorithm provided in the present publication.
If at least one metabolic criterion is present, but no other causes of steatosis, then that patient has MASLD. The three other metabolic subtypes include MetALD (2-3 drinks per day for women and 3-4 drinks per day for men), ALD (more than 3 drinks per day for women and more than 4 drinks per day for men), and monogenic miscellaneous drug-induced liver injury (DILI).
Patients without metabolic criteria can also be classified with monogenic miscellaneous DILI with no caveat, whereas patients with metabolic criteria need only consume 2 or 3 drinks per day for women or 3-4 drinks per day for men, respectively, to be diagnosed with ALD.
Finally, patients with no metabolic criteria or other cause of steatosis should be characterized by cryptogenic SLD.
“While renaming and redefining the disease was needed, the implementation is not without challenges,” Dr. Allen and colleagues wrote. “A more complex classification may add confusion in the mind of nonhepatology providers when awareness and understanding of the implications of SLD are already suboptimal.”
Still, they predicted that the new naming system could lead to several positive outcomes, including improved SLD screening among individuals with metabolic risk factors, more accurate phenotyping of patients with moderate alcohol consumption, increased disease awareness in nonhepatology practices, and improved multidisciplinary collaboration.
Only time will tell whether these benefits come to fruition, Dr. Allen and colleagues noted, before closing with a quote: “In the words of Jean Piaget, the developmental psychologist of the 20th century, who coincidentally died the year the term NASH was coined, ‘Scientific knowledge is in perpetual evolution; it finds itself changed from one day to the next.’”
The authors disclosed no conflicts of interest.
Nonalcoholic fatty liver disease (NAFLD) should now be referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), according to a recent commentary by leading hepatologists.
This update, which was determined by a panel of 236 panelists from 56 countries, is part of a broader effort to rebrand “fatty liver disease” as “steatotic liver disease” (SLD), reported lead author Alina M. Allen, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
Writing in Gastroenterology, they described a range of reasons for the nomenclature changes, from the need for better characterization of disease subtypes, to the concern that the term “fatty” may be perceived as stigmatizing by some patients.
“The scientific community and stakeholder organizations associated with liver diseases determined there was a need for new terminology to cover liver disease related to alcohol alone, metabolic risk factors (until recently termed NAFLD/nonalcoholic steatohepatitis [NASH]) alone, the combination of alcohol and metabolic risk factors, and hepatic steatosis due to other specific etiologies,” the authors wrote.
Naming conventions in this area have been flawed since inception, Dr. Allen and colleagues wrote, noting that “nonalcoholic” is exclusionary rather than descriptive, and is particularly misplaced in the pediatric setting. These shortcomings could explain why the term “NASH” took more than a decade to enter common usage, they suggested, and why the present effort is not the first of its kind.
“There have been several movements to change the nomenclature [of NAFLD], including most recently to ‘metabolic dysfunction–associated fatty liver disease’ (MAFLD), a term that received limited traction,” the authors wrote.
Still, a change is needed, they added, as metabolic dysfunction is becoming increasingly common on a global scale, driving up rates of liver disease. Furthermore, in some patients, alcohol consumption and metabolic factors concurrently drive steatosis, suggesting an intermediate condition between alcohol-related liver disease (ALD) and NAFLD that is indescribable via current naming conventions.
SLD (determined by imaging or biopsy) now comprises five disease subtypes that can be determined via an algorithm provided in the present publication.
If at least one metabolic criterion is present, but no other causes of steatosis, then that patient has MASLD. The three other metabolic subtypes include MetALD (2-3 drinks per day for women and 3-4 drinks per day for men), ALD (more than 3 drinks per day for women and more than 4 drinks per day for men), and monogenic miscellaneous drug-induced liver injury (DILI).
Patients without metabolic criteria can also be classified with monogenic miscellaneous DILI with no caveat, whereas patients with metabolic criteria need only consume 2 or 3 drinks per day for women or 3-4 drinks per day for men, respectively, to be diagnosed with ALD.
Finally, patients with no metabolic criteria or other cause of steatosis should be characterized by cryptogenic SLD.
“While renaming and redefining the disease was needed, the implementation is not without challenges,” Dr. Allen and colleagues wrote. “A more complex classification may add confusion in the mind of nonhepatology providers when awareness and understanding of the implications of SLD are already suboptimal.”
Still, they predicted that the new naming system could lead to several positive outcomes, including improved SLD screening among individuals with metabolic risk factors, more accurate phenotyping of patients with moderate alcohol consumption, increased disease awareness in nonhepatology practices, and improved multidisciplinary collaboration.
Only time will tell whether these benefits come to fruition, Dr. Allen and colleagues noted, before closing with a quote: “In the words of Jean Piaget, the developmental psychologist of the 20th century, who coincidentally died the year the term NASH was coined, ‘Scientific knowledge is in perpetual evolution; it finds itself changed from one day to the next.’”
The authors disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Is There a Safe Alcohol Limit in Early Liver Disease?
TOPLINE:
Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.
METHODOLOGY:
- Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
- They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
- Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.
TAKEAWAY:
- During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
- After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
- In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
- No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.
IN PRACTICE:
“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”
SOURCE:
The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.
LIMITATIONS:
The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.
DISCLOSURES:
The study did not list funding. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.
METHODOLOGY:
- Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
- They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
- Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.
TAKEAWAY:
- During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
- After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
- In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
- No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.
IN PRACTICE:
“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”
SOURCE:
The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.
LIMITATIONS:
The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.
DISCLOSURES:
The study did not list funding. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.
METHODOLOGY:
- Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
- They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
- Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.
TAKEAWAY:
- During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
- After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
- In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
- No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.
IN PRACTICE:
“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”
SOURCE:
The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.
LIMITATIONS:
The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.
DISCLOSURES:
The study did not list funding. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
Exploring the impact of substance use on liver transplantation
Dear colleagues,
With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?
Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.
We welcome your thoughts on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.
Liver transplantation in the setting of alcohol-related liver disease
BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD
Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).
The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.
One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.
The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.
References
Tapper E. BMJ. 2018;362: k2817
Louvet A. Lancet Gastro Hep. 2022;7(5):416-25
Lee B. Gastroenterology. 2018;155:422-30
Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)
High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants
BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD
Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.
Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.2 Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.3
The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.2 Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.
The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.4
The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.5 In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.
The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.
Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.
REFERENCES
1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.
2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.
3. Page, RL. Circulation. 2020;142(10):e131-e152.
4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.
5. Zhu, J. Transplantation. 2018;102(3):433-439.
Dear colleagues,
With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?
Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.
We welcome your thoughts on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.
Liver transplantation in the setting of alcohol-related liver disease
BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD
Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).
The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.
One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.
The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.
References
Tapper E. BMJ. 2018;362: k2817
Louvet A. Lancet Gastro Hep. 2022;7(5):416-25
Lee B. Gastroenterology. 2018;155:422-30
Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)
High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants
BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD
Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.
Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.2 Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.3
The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.2 Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.
The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.4
The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.5 In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.
The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.
Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.
REFERENCES
1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.
2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.
3. Page, RL. Circulation. 2020;142(10):e131-e152.
4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.
5. Zhu, J. Transplantation. 2018;102(3):433-439.
Dear colleagues,
With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?
Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.
We welcome your thoughts on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.
Liver transplantation in the setting of alcohol-related liver disease
BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD
Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).
The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.
One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.
The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.
References
Tapper E. BMJ. 2018;362: k2817
Louvet A. Lancet Gastro Hep. 2022;7(5):416-25
Lee B. Gastroenterology. 2018;155:422-30
Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)
High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants
BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD
Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.
Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.2 Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.3
The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.2 Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.
The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.4
The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.5 In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.
The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.
Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.
REFERENCES
1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.
2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.
3. Page, RL. Circulation. 2020;142(10):e131-e152.
4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.
5. Zhu, J. Transplantation. 2018;102(3):433-439.
Hepatologist finds purpose as health equity advocate for LGBTQI+
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
NAFLD familial risk score outperforms FIB-4 index for identifying advanced fibrosis
By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points). 
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points).
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points).
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY