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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
Statins and the liver: Not harmful and perhaps beneficial
, including glucose intolerance and hyperlipidemia. A lingering concern about potential hepatotoxicity has resulted in widespread reluctance to prescribe statins to treat hyperlipidemia in patients with liver disease; however, their safety in this setting has been documented in the literature as well as in clinical practice. Therefore, statins should not be withheld in patients with liver disease when indicated — with a few caveats. Baseline liver chemistries should be obtained. After initiation of statin therapy, a modest rise in serum aminotransferase levels may occur but is not an indication to discontinue the drug. In fact, monitoring of liver biochemical tests more frequently than is appropriate for any patient with chronic liver disease is unnecessary. The role of statins in cirrhosis may even expand, as recent reports suggest that statin use in patients with cirrhosis may slow the progression of liver disease and reduce the frequency of complications, such as hepatocellular carcinoma. These observations, however, require confirmation before statins can be suggested for any indication other than treating hyperlipidemia in patients with chronic liver disease, and statins are generally not appropriate in patients with decompensated cirrhosis.
Pearls from the Pros was published in Gastro Hep Advances .
Dr. Friedman is the Anton R. Fried, MD, Chair of the Department of Medicine at Newton-Wellesley Hospital in Newton, Mass., and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University, Boston. Dr. Martin is chief of the division of digestive health and liver diseases at the University of Miami, where he is the Mandel Chair of Gastroenterology. The authors disclose no conflicts.
, including glucose intolerance and hyperlipidemia. A lingering concern about potential hepatotoxicity has resulted in widespread reluctance to prescribe statins to treat hyperlipidemia in patients with liver disease; however, their safety in this setting has been documented in the literature as well as in clinical practice. Therefore, statins should not be withheld in patients with liver disease when indicated — with a few caveats. Baseline liver chemistries should be obtained. After initiation of statin therapy, a modest rise in serum aminotransferase levels may occur but is not an indication to discontinue the drug. In fact, monitoring of liver biochemical tests more frequently than is appropriate for any patient with chronic liver disease is unnecessary. The role of statins in cirrhosis may even expand, as recent reports suggest that statin use in patients with cirrhosis may slow the progression of liver disease and reduce the frequency of complications, such as hepatocellular carcinoma. These observations, however, require confirmation before statins can be suggested for any indication other than treating hyperlipidemia in patients with chronic liver disease, and statins are generally not appropriate in patients with decompensated cirrhosis.
Pearls from the Pros was published in Gastro Hep Advances .
Dr. Friedman is the Anton R. Fried, MD, Chair of the Department of Medicine at Newton-Wellesley Hospital in Newton, Mass., and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University, Boston. Dr. Martin is chief of the division of digestive health and liver diseases at the University of Miami, where he is the Mandel Chair of Gastroenterology. The authors disclose no conflicts.
, including glucose intolerance and hyperlipidemia. A lingering concern about potential hepatotoxicity has resulted in widespread reluctance to prescribe statins to treat hyperlipidemia in patients with liver disease; however, their safety in this setting has been documented in the literature as well as in clinical practice. Therefore, statins should not be withheld in patients with liver disease when indicated — with a few caveats. Baseline liver chemistries should be obtained. After initiation of statin therapy, a modest rise in serum aminotransferase levels may occur but is not an indication to discontinue the drug. In fact, monitoring of liver biochemical tests more frequently than is appropriate for any patient with chronic liver disease is unnecessary. The role of statins in cirrhosis may even expand, as recent reports suggest that statin use in patients with cirrhosis may slow the progression of liver disease and reduce the frequency of complications, such as hepatocellular carcinoma. These observations, however, require confirmation before statins can be suggested for any indication other than treating hyperlipidemia in patients with chronic liver disease, and statins are generally not appropriate in patients with decompensated cirrhosis.
Pearls from the Pros was published in Gastro Hep Advances .
Dr. Friedman is the Anton R. Fried, MD, Chair of the Department of Medicine at Newton-Wellesley Hospital in Newton, Mass., and assistant chief of medicine at Massachusetts General Hospital, and a professor of medicine at Harvard Medical School and Tufts University, Boston. Dr. Martin is chief of the division of digestive health and liver diseases at the University of Miami, where he is the Mandel Chair of Gastroenterology. The authors disclose no conflicts.
AGA CPU updates usage of vasoactive drugs, IV albumin, for cirrhosis
The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.
These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
Variceal Hemorrhage
Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.
“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.
In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.
The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.
“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
Ascites and Spontaneous Bacterial Peritonitis
In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.
Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.
Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.
The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
Acute Kidney Injury and Hepatorenal Syndrome
In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”
The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.
Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.
The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.
The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.
These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
Variceal Hemorrhage
Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.
“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.
In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.
The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.
“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
Ascites and Spontaneous Bacterial Peritonitis
In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.
Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.
Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.
The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
Acute Kidney Injury and Hepatorenal Syndrome
In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”
The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.
Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.
The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.
The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.
These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
Variceal Hemorrhage
Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.
“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.
In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.
The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.
“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
Ascites and Spontaneous Bacterial Peritonitis
In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.
Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.
Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.
The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
Acute Kidney Injury and Hepatorenal Syndrome
In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”
The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.
Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.
The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.
FROM GASTROENTEROLOGY
Fewer than 1 out of 4 patients with HCV-related liver cancer receive antivirals
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
AT THE LIVER MEETING
Taste and smell changes linked with worse QOL and cognition in cirrhosis, renal failure
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
AT THE LIVER MEETING
COVID livers are safe for transplant
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
AT THE LIVER MEETING