Drug-Induced Liver Injury due to Medications for Alcohol Use Disorder: Results from the DILIN Prospective Study

Abstract

Objectives: Concerns about drug-induced liver injury (DILI) may deter physicians from prescribing medications for alcohol use disorder (MAUD). We aim to explore DILI due to MAUD in Drug-Induced Liver Injury Network (DILIN) prospective study. Methods: High-confidence DILI cases (ie, definite, highly likely, or probable) due to MAUD in DILIN prospective study (2004-2024) were included. Demographic, clinical, laboratory data, and 6-month outcomes were analyzed. HLA allele frequency (AF) of disulfiram cases was compared to matched controls with DILI due to non-MAUD (DILI controls). Results: Among 1975 high-confidence cases, 13 were attributed to MAUD (11 disulfiram; 1 naltrexone and 1 baclofen; and none from acamprosate). Median age was 45 years, with 77% female and 85% White. All had hepatocellular injury. In disulfiram group, the median time for DILI occurrence was 34 days. Eight patients developed jaundice, with 3 fatal or near-fatal cases (2 liver transplantation and 1 liver-related death). Five (71%) patients with severe or fatal disulfiram DILI had underlying liver disease. AF for HLA-C01:02 (OR, 6.29; P = 0.02) and DRB109:01 (OR, 10.16; P = 0.02) were significantly higher in disulfiram cases than in DILI controls. DILI from baclofen and naltrexone was mild and self-limited with no chronic DILI. Conclusions: Disulfiram is the leading cause of DILI among MAUD and is most common in women. Disulfiram can cause severe DILI and is associated with HLA-C01:02 and DRB109:01. Baclofen and naltrexone can cause mild to moderate self-limited DILI. There were no cases of acamprosate. These findings suggest DILI due to MAUD are less frequent.