Baclofen vs Acamprosate in Alcohol-Associated Cirrhosis: Alimentary Pharmacology & Therapeutics | March 2026

Introduction

Management of alcohol use disorder in patients with cirrhosis remains a clinical challenge, where drug safety is as critical as efficacy. Acamprosate is generally preferred due to renal clearance, while baclofen has been considered safe even in advanced liver disease. However, comparative real-world safety data between these two commonly used agents in compensated alcohol-associated cirrhosis have been limited.

Problem Statement

Despite guideline endorsement of both baclofen and acamprosate, uncertainty persists regarding their relative hepatic safety. Clinicians often face a dilemma in choosing therapy, particularly in patients at risk of decompensation, where even small differences in adverse outcomes can significantly impact prognosis.

Summary

This large, multicenter, real-world cohort study using a target trial emulation framework compared baclofen and acamprosate in compensated alcohol-associated cirrhosis. After robust propensity matching, baclofen was associated with a higher incidence of major adverse liver outcomes at one year compared to acamprosate (34.3% vs 27.4%). Notably, the increased risk was primarily driven by a higher incidence of hepatic encephalopathy, while other decompensation events and mortality did not differ significantly. The risk appeared more pronounced in older patients.

These findings suggest that while baclofen remains an option, acamprosate may be the safer first-line agent in compensated cirrhosis, particularly in patients at risk for encephalopathy. This study provides important real-world evidence to guide individualised therapeutic decision-making in this vulnerable population.