Kimberly A. Brown, MD

Liver Lineup: Unmet Needs and Evolving Standards in Alcohol-Associated Liver Disease, With Jessica Mellinger, MD

Liver Lineup: Updates and Unfiltered Insights

, hosts Nancy Reau, MD, and Kimberly Brown, MD, are joined by guest Jessica Mellinger, MD, to discuss rising prevalence, new care models, and evolving concepts in alcohol-associated liver disease (ALD).

Mellinger begins by addressing the troubling rise in alcohol use and ALD. Despite widespread healthcare engagement, she says patients with ALD are often diagnosed late, underscoring the need for proactive screening approaches that combine assessments of both liver health and alcohol use. She also notes that defined screening models and pathways developed for MASLD could be adapted for ALD to improve early identification and intervention.

A key part of the discussion centers on Mellinger’s pioneering integrated clinic model, which brings hepatology and addiction psychiatry together in a single, co-located setting. She explains that addressing liver health and alcohol use disorder alongside underlying drivers such as anxiety, depression, insomnia, and chronic pain is critical—and that siloed systems of care have historically failed these patients.

The conversation also explores the emergence of MetALD and the overlap between metabolic and alcohol-associated liver disease. Mellinger notes that while definitions continue to evolve, understanding the interplay between metabolic dysfunction and alcohol use will be essential for tailoring therapies. GLP-1 receptor agonists, already transforming the metabolic liver disease landscape with the recent FDA approval of semaglutide for MASH, are showing early promise for ALD as well, with some patients reporting reduced alcohol cravings and improved liver parameters.

Turning to transplantation, Mellinger reflects on the progress since the Dallas Criteria were introduced, highlighting shifting attitudes toward early liver transplant in carefully selected patients. She stresses the importance of moving beyond rigid sobriety thresholds toward a more patient-centered approach focused on post-transplant support and relapse management.

The trio emphasizes that progress in alcohol-associated liver disease depends on bridging the long-standing divide between hepatology and addiction medicine. With integrated care models gaining traction, evolving definitions like MetALD reshaping clinical thinking, and novel therapeutics such as GLP-1 receptor agonists offering new hope, the field may be entering a pivotal era.

Editors’ Note: Editors’ note: Relevant disclosures for 

 include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for 

 include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for 

Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed October 14, 2025. 

https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

Asrani SK, Trotter J, Lake J, et al. Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis. Liver Transpl. 2020;26(1):127-140. 

Podcasts

Mellinger joins Liver Lineup to discuss current shortcomings in ALD diagnosis and care, the importance of addressing underlying alcohol use disorder, and more.

Liver Lineup: GLP-1 RAs and FGF21s for MASH, with Mary Rinella, MD

, hosts Nancy Reau, MD, and Kimberly Brown, MD, sit down with Mary (Maru) Rinella, MD, a professor of medicine and director of Clinical Trials and the Metabolic and Fatty Liver Program at the University of Chicago, to discuss the rapidly evolving therapeutic landscape for 

metabolic dysfunction-associated steatohepatitis (MASH)

The conversation opens with a discussion about GLP-1 receptor agonists, which Rinella notes are already ubiquitous in her practice, with nearly 60% of patients being on one by the time they see her because of the overlap of comorbidities like diabetes and obesity with MASLD. She explains that the liver benefits of these agents appear to be primarily mediated by weight loss, though findings from the ESSENCE trial of Novo Nordisk’s semaglutide have demonstrated resolution of steatohepatitis and improvements in fibrosis.

Editors’ note: This episode was recorded prior to the FDA approval of semaglutide (Wegovy) injection 2.4 mg for the treatment of noncirrhotic MASH on August 15, 2025.

The conversation then shifts to strategies for integrating GLP-1 receptor agonists with resmetirom (Rezdiffra), the first FDA-approved agent for MASH. Rinella emphasizes the importance of staggering initiation, typically waiting 3 to 6 months before layering therapies, to both monitor for side effects and determine which drug is driving clinical response. She highlights the need for individualized, patient-centered strategies based on comorbidities and disease severity.

Looking ahead, the discussion turns to next-generation incretin therapies, including dual and triple agonists such as tirzepatide, survodutide, and retatrutide. While early-phase studies suggest significant weight loss and metabolic benefits, all 3 experts note phase 3 data are needed to establish their antifibrotic efficacy. The group also notes challenges in advanced liver disease: while weight loss can improve fibrosis, it also poses important implications for sarcopenia risk and acceleration, a trade-off that is particularly concerning in the context of cirrhosis, where malnutrition already heightens risk.

The experts also delve into FGF21 analogues, a class Rinella describes as one of the most promising in development with agents such as efruxifermin and pegozafermin showing some of the largest antifibrotic signals to date. Although recent cirrhosis trials were limited by short follow-up periods, Rinella expresses confidence that longer studies will confirm meaningful fibrosis improvements, additionally pointing to emerging research suggesting possible effects on alcohol consumption, opening new avenues for treatment in patients with overlapping metabolic and alcohol-related liver disease.

Finally, the group considers where the field is headed. Within the next decade, Rinella says she anticipates a much richer therapeutic armamentarium that could allow most patients with MASH to receive targeted treatment. However, she cautions that decompensated cirrhosis remains an area of unmet need, with no therapies yet convincingly effective.

Brooks A. Semaglutide Improves Steatohepatitis, Fibrosis in Phase 3 MASH Trial. 

. April 30, 2025. Accessed August 20, 2025. 

https://www.hcplive.com/view/semaglutide-improves-steatohepatitis-fibrosis-phase-3-mash-trial

Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. 

. August 15, 2025. Accessed August 20, 2025. 

Brooks A. Efruxifermin Shows Potential for Fibrosis Reduction in Phase 2b MASH Cirrhosis Trial. 

. May 9, 2025. Accessed August 20, 2025. 

https://www.hcplive.com/view/exfruxifermin-misses-primary-endpoint-phase-2b-compensated-mash-cirrhosis-trial

Hosts Nancy Reau and Kimberly Brown are joined by Mary Rinella to discuss the evolving MASH treatment landscape with GLP-1s and FGF21s in development.

Liver Lineup: Progress, Policy, and Barriers in Hepatitis C Elimination

Liver Lineup: Updates & Unfiltered Insights

, hosts Kimberly Brown, MD, a professor of Medicine at Michigan State University and Wayne State University, associate medical director of the Henry Ford Hospital Transplant Institute, and medical director of Transplant Outreach Services at Henry Ford Hospital, and Nancy Reau, MD, a professor of internal medicine, the Richard B. Capps Chair of Hepatology, associate director of solid organ transplantation, and the section chief of hepatology at Rush University Medical Center, discuss the progress and persistent challenges in eliminating 

With highly effective, short-course oral therapies now available, Brown and Reau emphasize that curing HCV is more achievable than ever. The discussion explores the major policy, clinical, and structural milestones enabling this effort—and the critical gaps in diagnosis, treatment access, and health policy that still impede progress.

Reau opens by emphasizing the revolutionary nature of curative HCV therapies, which not only improve individual health outcomes but also reduce transmission, presenting a rare opportunity for public health impact on a global scale. She and Brown discuss how national and international efforts, including World Health Organization goals and US legislation, have aligned to prioritize viral hepatitis elimination.

Specifically, the hosts discuss the role of the US Preventive Services Task Force and the Affordable Care Act in establishing HCV screening as a covered preventive service. Outlining the evolution from birth cohort screening to universal screening for adults 18 and over, Reau and Brown discuss a recent legal challenge to the Affordable Care Act’s preventive service mandate that threatened access to HCV screening. The Supreme Court’s 6–3 decision to uphold this provision was, in their view, a critical win for public health and HCV elimination.

Despite these advances, both experts acknowledge major challenges remain in the HCV care cascade. Many patients are lost between screening and cure, often due to provider restrictions, system fragmentation, and lack of prioritization. They emphasize the need for government-backed elimination efforts, drawing lessons from successful national programs in countries like Egypt and Georgia.

The conversation also underscores the role of grassroots advocacy, emphasizing the critical role clinicians and patients alike can play in supporting federal hepatitis elimination legislation. Most importantly, they encourage patients to share their stories with legislators—a strategy proven effective in other public health movements, including HIV.

Reau additionally calls upon listeners to write to their local senators to support bipartisan legislation from senators Bill Cassidy (R-LA) and Chris Van Hollen (D-MD) to eliminate hepatitis C using the following link: 

Ask Senators to Cosponsor the Cure Hepatitis C Act

Editors’ note: Relevant Disclosures for 

 include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal.

Hosts Kimberly Brown and Nancy Reau discuss policy, clinical, and structural milestones enabling HCV elimination efforts and critical gaps impeding progress.

Liver Lineup: Advances in MASH, PSC, and PBC Care at EASL 2025

, hosts Kimberly Brown, MD, a professor of Medicine at Michigan State University and Wayne State University, associate medical director of the Henry Ford Hospital Transplant Institute, and medical director of Transplant Outreach Services at Henry Ford Hospital, and Nancy Reau, MD, a professor of internal medicine, the Richard B. Capps Chair of Hepatology, associate director of solid organ transplantation, and the section chief of hepatology at Rush University Medical Center, continue their discussion on notable abstracts presented at the 2025 European Association for the Study of the Liver (EASL) Congress.

Check out part 1 of Liver Lineup’s EASL recap 

The hosts highlight an additional 3 abstracts of note from the meeting, starting with findings from the LITMUS study, a multicenter effort to identify noninvasive biomarkers that can accurately stage patients with at-risk 

, particularly for inclusion in clinical trials. While many patients had baseline imaging and biomarker data correlated with liver biopsy, only the NIS4-2 test—a proprietary combination of 2 biomarkers—showed promise in identifying this “at-risk” group, though both hosts note that it is not yet commercially available.

Results showed widely used measures such as FIB-4 and VCTE alone underperformed for early-stage disease, to which Brown and Reau both express disappointment that reliable, accessible tools for frontline providers are still lacking—creating barriers to early referral and trial enrollment.

, the hosts discuss a promising interim analysis of an ongoing norursodeoxycholic acid trial. At week 96, results showed the bile acid therapy significantly reduced alkaline phosphatase levels compared to placebo, particularly in patients not receiving ursodeoxycholic acid. Notably, the hosts point out 25% of treated patients showed an improvement in fibrosis stage, and fewer progressed compared to placebo. Although early, Brown says the results suggest this agent may offer hope for a disease that currently has no approved therapy and a high risk of complications like cholangiocarcinoma.

Finally, Brown and Reau review a presentation on seladelpar, a newly approved PPAR agonist for the treatment of 

. In the study, investigators used the GLOBE score—a validated tool predicting transplant-free survival—to assess outcomes and found patients on seladelpar had significantly improved GLOBE scores, reinforcing the long-term benefit of the drug beyond surrogate markers like ALP and bilirubin. While both hosts admit they do not routinely calculate the score in clinical practice, they emphasize its value in post-marketing evaluation, especially given the challenges of proving outcome benefit in a slowly progressive disease like PBC.

Reau concludes the episode with optimism about the progress being made for PBC and hope that similar breakthroughs for PSC, alcohol-associated liver disease, and MASLD are on the horizon.

Editors’ note: Relevant Disclosures for Reau include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for Brown include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal.

In the second part of a 2-part episode, hosts Kimberly Brown and Nancy Reau break down 3 more notable abstracts from the 2025 EASL Congress.

Kimberly A. Brown, MD

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