Assessing Major Adverse Liver Outcomes With Baclofen Compared to Acamprosate in Compensated Alcohol‐Associated Cirrhosis

Background Acamprosate is generally considered safe in patients with liver disease because it is renally cleared. Baclofen has been shown to be safe and effective in patients with alcohol use disorder and alcohol‐associated cirrhosis. Both medications are guideline‐endorsed pharmacotherapies for patients with alcohol‐associated cirrhosis. However, the safety of baclofen relative to acamprosate remains uncertain. Aims To compare the safety profiles of baclofen and acamprosate in patients with alcohol‐associated cirrhosis. Methods We conducted a nationwide, multicenter cohort study using a target trial emulation framework. Adults with compensated alcohol‐associated cirrhosis who received a first prescription of baclofen or acamprosate within 6 months of diagnosis were included. Propensity score matching (1:1) was used to balance 60 covariates. The primary outcome was major adverse liver outcomes (MALO), defined as a composite of hepatic decompensation events within 12 months. Secondary outcomes included individual decompensation events and mortality. Results After matching, 571 baclofen and 571 acamprosate initiators were analysed. The 1‐year incidence of MALO was higher in the baclofen group (34.3%) than in the acamprosate group (27.4%), corresponding to a hazard ratio (HR) of 1.32 (95% CI, 1.02–1.70). Among individual events, baclofen was associated with a higher risk of hepatic encephalopathy (HR 1.80; 95% CI, 1.21–2.69). No significant differences in other individual events or mortality were observed. Subgroup analyses suggested greater risk among patients aged 56–70 years. Conclusions In this large real‐world study, baclofen was associated with a higher risk of hepatic encephalopathy compared with acamprosate in patients with compensated alcohol‐associated cirrhosis.