Liver Lineup: New MASLD and PBC Agents, PEth Testing, and HBV Functional Cure at EASL 2025

In this episode of Liver Lineup: Updates & Unfiltered Insights, hosts Kimberly Brown, MD, division chief of gastroenterology and hepatology and the associate medical director of the Henry Ford Hospital Transplant Institute at Henry Ford Hospital and a professor of medicine at Wayne State University, 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, highlight 4 key abstracts presented at the 2025 European Association for the Study of the Liver (EASL) Congress.

The hosts begin by discussing data presented on a new fibroblast growth factor 21 (FGF21) analog, efimosfermin alfa, citing the agent’s fast-acting impact on fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH). Brown highlights its once-monthly subcutaneous administration and notes reductions in pro-fibrotic markers as soon as 4 weeks, indicating early improvements in fibrosis that were sustained through week 24 of the study.

Reau calls attention to the antifibrotic nature of efimosfermin alfa, citing delayed antifibrotic effects in other currently approved agents as well as agents that are currently in clinical development and expected to eventually earn approval. The duo also notes the favorable safety profile of the drug, describing the lack of severe side effects observed thus far.

The second abstract they highlight from EASL examines the use of phosphatidylethanol (PEth) testing to monitor alcohol intake in patients with alcohol-associated liver disease and confirm their self-reported alcohol consumption using an objective, blood-based biomarker. Brown describes discordance between patients’ reported alcohol consumption and their PEth levels in the study, noting the significance of now having confirmatory testing that can better categorize these patients and aid risk stratification in the context of clinical trials.

Reau notes that her institution primarily conducts PEth testing in patients being considered for transplantation, to which Brown asserts that more clinical trials should be using this tool to increase understanding of its value in clinical practice. She also describes its use in patients presenting as donors.

Reau then introduces the third abstract examining data from the RETRACT-B cohort, a global, multicenter observational project evaluating the feasibility of stopping nucleos(t)ide analog therapy in chronic hepatitis B patients with long-term viral suppression. She explains that while current long-term maintenance HBV treatments are “excellent” at viral suppression, patients often want to know that they do not need to take medication for forever.

RETRACT-B findings presented at EASL suggest those with low surface antigen levels have the greatest chance of success, but reaffirm that discontinuation is not for everyone – some patients experience recurrence, flares, and decompensation events. Both experts highlight treatment discontinuation in patients with cirrhosis, something they say they likely would not consider for these patients due to the risk of decompensation.

The fourth and final EASL abstract Brown and Reau highlight is the phase 3 GLISTEN trial of linerixibat in patients with primary biliary cholangitis (PBC) and cholestatic pruritus, data Reau refers to as a “success story,” highlighting early, significant, and sustained itch relief with use of the ileal bile acid transporter (IBAT) inhibitor.

Despite these positive data, both experts note that IBAT inhibitors are currently approved for Alagille syndrome and progressive familial intrahepatic cholestasis but have not yet been granted approval for pruritus in PBC.

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.