Q4 2025 Recap: Hepatology News and Updates

The fourth quarter of 2025 underscored how rapidly hepatology is evolving at the intersection of metabolic disease, public health policy, and clinical standards of care.

Q4 opened with updated American Association for the Study of Liver Diseases (AASLD) practice guidance on semaglutide for metabolic dysfunction-associated steatohepatitis (MASH), reflecting the growing role of incretin-based therapies in metabolic dysfunction-associated steatotic liver disease (MASLD) management, alongside encouraging phase 2 data for next-generation dual agonists such as mazdutide. Diagnostic innovation also moved to the forefront, with prospective data from the ALTUS study suggesting that multi-target blood testing may meaningfully outperform ultrasound for early hepatocellular carcinoma detection in at-risk populations.

As the year closed, attention turned to high-impact policy and practice updates with broad implications for clinicians. A narrowly passed Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) vote reshaped recommendations around infant hepatitis B vaccination, prompting renewed discussion about implementation and long-term prevention strategies, while AASLD and AST released comprehensive new guidelines addressing both liver transplant candidacy and post-transplant management. Rounding out the quarter, pemvidutide’s progression toward phase 3 development reinforced momentum in the MASH pipeline, and expert dialogue on alcohol-associated liver disease highlighted persistent unmet needs and the urgency of integrating liver care with effective treatment of alcohol use disorder.

Check out this recap of what made headlines in Q4 of 2025:

AASLD Releases Updated Practice Guidance on Semaglutide (Wegovy) for MASH

On November 7, 2025, the AASLD released an updated practice guidance on semaglutide (Wegovy) therapy for MASH. Published in Hepatology, the document serves as an update to the 2023 AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease (NAFLD), now known as MASLD, and provides recommendations on patient selection, comorbidity management, and monitoring the safety and effectiveness of semaglutide for MASH.

Mazdutide Significantly Reduces Liver Fat, Improves Metabolic Markers in MASLD, Obesity

Phase 2 data highlight the benefit of mazdutide, a once-weekly dual agonist of the glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, on liver fat content reduction, steatosis resolution, and metabolic marker improvement in patients with MASLD and obesity. By 32 weeks, investigators observed reductions in liver fat content across all mazdutide groups compared with placebo (P <.01), with mean percent change from baseline in liver fat content of -53.5% (standard error [SE], 5.4%) with 3/6 mg, -67.7% (SE, 4.0%) with 10 mg, -68.8% (SE, 4.8%) with 16 mg vs -14.1% (SE, 6.7%) compared with placebo.

ALTUS: Multi-Target Blood Outperforms Ultrasound for HCC, With Binu John, MD, MPH

A new multi-target blood test, Exact Sciences’ Oncoguard® Liver blood test, delivers superior early-stage and overall sensitivity for hepatocellular carcinoma (HCC) compared to standard of care abdominal ultrasound, according to findings from the prospective multicenter ALTUS study. The data were presented by Binu John, MD, MPH, an associate professor of medicine and chief of gastroenterology and hepatology at the University of Miami, at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025, and showed the higher sensitivity demonstrated by mt-HBT for detecting early-stage HCC, defined by Milan Criteria, in at-risk patients (66.7%) compared with ultrasound (22.2%).

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

AASLD Releases New Liver Transplantation Practice Guidelines on Candidacy, Management

On December 17, 2025, the AASLD and AST released 2 new practice guidelines on evaluating adult liver transplant candidates and managing non-graft complications that drive long-term outcomes following liver transplantation.

“AASLD’s practice guidelines and guidances are invaluable tools for clinicians worldwide. Together, these guidelines represent a comprehensive, patient-centered roadmap for adult liver transplantation,” Grace Su, MD, President of AASLD, said in a statement.1 “By addressing both who should be considered for transplant and how patients should be cared for long after surgery, we aim to support better outcomes, improved quality of life, and more consistent care for patients worldwide.”

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

On December 19, 2025, Altimmune announced positive topline results from the phase 2b IMPACT trial of pemvidutide, a balanced 1:1 glucagon/GLP-1 dual receptor agonist, in patients with MASH at 48 weeks. Topline 48-week data showed treatment with pemvidutide achieved statistically significant improvements across treatment arms in key noninvasive tests, including Enhanced Liver Fibrosis (ELF) and Liver Stiffness Measurement (LSM), versus placebo. Altimmune additionally announced that it held a productive End-of-Phase 2 meeting with the FDA resulting in alignment on the parameters for a registrational phase 3 trial of pemvidutide for MASH patients with moderate to advanced liver fibrosis.

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

In this episode of 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). The group delves into current shortcomings in ALD diagnosis and care, the importance of addressing underlying alcohol use disorder, and more.