MASH Therapies Show Fibrosis Signal in ALD, With Vijay Shah, MD

Drugs developed for metabolic dysfunction-associated steatohepatitis (MASH) may also improve fibrosis in alcohol-related liver disease (ALD), according to Vijay Shah, MD, who presented phase 2 randomized trial results at The Liver Meeting 2026 in Denver, Colorado.

“If you took a liver of somebody who had MASLD or MASH and somebody who had alcohol, they looked the same,” Shah, a consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota, told HCP Live. That histologic overlap is part of why investigators tested agents targeting 3 pathways already being studied in MASH and obesity.

How Did MASH Therapies Affect Fibrosis in ALD?

The multinational, placebo-controlled trial randomized 270 participants with heavy alcohol use and advanced liver disease to 28 weeks of once-weekly zalfermin, an FGF-21 analogue; cagrilintide, an amylin analogue; semaglutide (Wegovy), a GLP-1 receptor agonist; or 1 of 2 combinations. All active treatment arms met the primary end point, reducing Enhanced Liver Fibrosis (ELF) score compared with placebo, with consistent improvements in liver stiffness and PRO-C3. Investigators describe it as the first randomized trial to show that pharmacologic treatment can improve fibrosis biomarkers in ALD.1

The finding addresses a long-standing gap. Sustained abstinence remains the cornerstone of ALD management, and no approved therapies target the underlying fibrogenic process.1,2 Shah points to stigma and the biologic complexity of alcohol-related injury as reasons progress has lagged.

Was the Benefit Driven by Reduced Drinking?

Alcohol consumption trended downward in every group, but without significant differences vs placebo, suggesting the benefit may stem in part from direct effects on the liver. Shah also explains why metabolic risk factors among many participants, consistent with the MetALD phenotype, may have contributed.3

Watch the full interview to hear Shah discuss the safety and tolerability profile in this heavily drinking population, the design challenges facing future trials, and how these investigational therapies might one day fit alongside treatment for alcohol use disorder.

References:

1. Shah V, Arab JP, Bataller R, et al. Effects of zalfermin, cagrilintide, and semaglutide on non-invasive fibrosis biomarkers in alcohol-related liver disease: a phase 2 randomized trial. Abstract 0087. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Jophlin LL, Singal AK, Bataller R, et al. ACG clinical guideline: alcohol-associated liver disease. Am J Gastroenterol. 2024;119(1):30-54. doi:10.14309/ajg.0000000000002572
3. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986. doi:10.1097/HEP.0000000000000520