2025 was a landmark year in hepatology, defined by regulatory milestones, therapeutic expansion, and growing clarity around how liver diseases may be diagnosed, treated, and studied moving forward. Across viral hepatitis, MASH/MASLD, and cholestatic liver diseases, the year reflected both long-awaited progress and ongoing recalibration as the field responded to new evidence, new approvals, and new uncertainties.

Regulatory momentum was especially visible in viral hepatitis and MASH. The FDA’s label expansion of glecaprevir/pibrentasvir for acute hepatitis C virus (HCV) marked a major advance in early intervention and cure, while the approval of semaglutide for noncirrhotic MASH reinforced the central role of metabolic therapies in liver disease management. At the same time, the FDA’s acceptance of FibroScan liver stiffness measurement as a reasonably likely surrogate endpoint signaled a potential inflection point for MASH drug development, complementing continued pipeline advances from agents such as pemvidutide and efruxifermin and reflecting a broader shift toward noninvasive assessment.

Despite these advances, 2025 was not defined by progress alone. The voluntary withdrawal of obeticholic acid for PBC underscored persistent safety and efficacy challenges in cholestatic disease, even as nebokitug moved closer to a registrational pathway for PSC. Policy decisions, including changes to CDC recommendations on infant hepatitis B vaccination, sparked debate and highlighted the evolving intersection of evidence, public health, and clinical practice. Together, these developments made 2025 a year of acceleration and reassessment, reshaping the hepatology landscape while setting the stage for the next era of innovation.

FDA News

FDA Approves Glecaprevir/Pibrentasvir (Mavyret) Label Expansion for Acute HCV

On June 11, 2025, the FDA approved a label expansion for AbbVie’s glecaprevir/pibrentasvir (Mavyret), an oral pangenotypic direct acting antiviral (DAA) therapy. With this decision, glecaprevir/pibrentasvir is now approved for the treatment of adults and pediatric patients ≥ 3 years of age with acute or chronic HCV infection without cirrhosis or with compensated cirrhosis.

The approval was supported by data from the phase 3, multicenter, single-arm prospective M20-350 study evaluating the safety and efficacy of glecaprevir/pibrentasvir 8-week treatment in adults with acute HCV infection. Of note, the decision made glecaprevir/pibrentasvir the first and only DAA therapy approved to treat patients with acute HCV in 8 weeks with a 96% cure rate.

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

On August 15, 2025, the FDA approved Novo Nordisk’s semaglutide (Wegovy) injection 2.4 mg for the treatment of adults with MASH with moderate to advanced fibrosis, but not with cirrhosis, in conjunction with a reduced calorie diet and increased physical activity. The decision made semaglutide the second-ever FDA-approved MASH therapeutic and was based on results from the phase 3 ESSENCE trial investigating the effects of once-weekly semaglutide 2.4 mg injection on liver histology in adults with MASH and moderate to advanced liver fibrosis at week 72.

FDA Accepts FibroScan Letter of Intent for Surrogate Endpoint in MASH Trials

On September 8, 2025, the FDA’s Center for Drug Evaluation and Research, Office of New Drugs accepted Echosens’ Letter of Intent for the qualification of Liver Stiffness Measurement (LSM) by VCTE (FibroScan) as a reasonably likely surrogate endpoint in clinical trials for MASH. The decision marked the first time the FDA accepted the initiation of the qualification process of a noninvasive test as a reasonably likely surrogate endpoint in drug development for MASH. The Letter of Intent included official letters of support from Eli Lilly, Boehringer Ingelheim, and Novo Nordisk.

Intercept Voluntarily Withdraws Obeticholic Acid (Ocaliva) for PBC From US Market

On September 11, 2025, Intercept Pharmaceuticals announced its decision to voluntarily withdraw obeticholic acid (Ocaliva) from the US market for the treatment of PBC following a request from the FDA, The Agency additionally placed a clinical hold on all Intercept clinical trials conducted under a US IND involving obeticholic acid.

Nebokitug (CM-101) Gets FDA Runway for PSC Approval

On February 19, 2025, Chemomab Therapeutics announced the successful completion of an end-of-phase 2 meeting with the FDA as well as alignment with the agency on the design of a single phase 3 registration study for nebokitug (CM-101) for the treatment of PSC.

“Until now, the pathway to drug approval in PSC has been problematic due to the lack of validated surrogate endpoints and clarity around primary efficacy endpoints for PSC registration trials. This has been a major hindrance to the development of effective therapies for PSC,” Christopher Bowlus, MD, the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, commented. “The agreed composite endpoint approach for the nebokitug trial enhances our chances of efficiently and accurately identifying the potential clinical benefits of this promising new drug.

Trial Updates and New Guidelines

Pemvidutide Shows Continued Antifibrotic Activity for MASH, Progresses to Phase 3 Trial

Topline 48-week data from the phase 2b IMPACT trial of pemvidutide, a balanced 1:1 glucagon/GLP-1 dual receptor agonist, in patients with MASH showed treatment with pemvidutide achieved statistically significant improvements across treatment arms in key noninvasive tests, including ELF and LSM, versus placebo. Of note, these data exhibited continued reductions from week 24 and provide evidence of continued improvement in antifibrotic activity with both treatment doses.

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

Efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of MASH, failed to significantly reduce fibrosis without worsening of MASH at 36 weeks in a phase 2b trial. Despite missing the trial’s primary endpoint, the 50 mg dose of efruxifermin may have possible benefit on fibrosis reduction at 96 weeks. Notably, efruxifermin also appeared to be associated with improvements in MASH-related histologic findings, noninvasive markers of liver injury and fibrosis, and markers of glucose and lipid metabolism.

CDC Changes Infant Hepatitis B Vaccine Recommendation

On December 5, 2025, the CDC ACIP voted 8 to 3 to recommend individual-based decision-making for parents deciding whether to give the hepatitis B vaccine, including the birth dose, to infants born to women who test negative for the virus.

For infants not receiving the birth dose, ACIP suggested in its recommendation that the initial dose be administered no earlier than 2 months of age. ACIP additionally voted to recommend that when evaluating the need for a subsequent hepatitis B vaccine dose in children, parents should consult with health care providers to decide whether to test antibody levels to hepatitis surface antigen to evaluate adequacy of protection through serology results.

Related: Clinical Concerns Over the ACIP Infant Hepatitis B Vaccine Decision, With Chari Cohen, DrPH, MPH

Feature Content/Podcasts

Celebrating 1 Year of Resmetirom, Progress in MASH/MASLD

In honor of the 1 year anniversary of resmetirom’s FDA approval, a trio of expert hepatologists examined updates and unmet needs in the management of MASH and MASLD, highlighting resmetirom’s impact on disease management and looking ahead to what might be next in the pipeline.

Liver Lineup: Innovations in Cholestatic Disease Management, With Kris Kowdley, MD

In this episode of Liver Lineup: Updates & Unfiltered Insights, Nancy Reau, MD, sits down with Kris Kowdley, MD, to discuss evolving approaches in cholestatic liver disease, with a particular focus on PBC diagnosis and shifting treatment goals.

2025 in Hepatology: New MASLD Therapies, HBV Updates, and More

As part of HCPLive’s This Year in Medicine series, the editorial team of HCPLive Hepatology invited 7 leading experts to weigh in on the most important advances of 2025. Their responses ranged from the long-awaited arrival of effective pharmacologic treatments for MASLD/MASH to renewed innovation in viral hepatitis, cholestatic liver diseases, portal hypertension, and alcohol-associated liver disease, as well as emerging noninvasive diagnostics, evolving disease definitions, AI-enabled pathology, and increasingly patient-centered care models.