Drug-induced Liver Injury Due to Medications for Alcohol Use Disorder: Results From the DILIN Prospective Study.

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-C*01:02 (OR, 6.29; P  = 0.02) and DRB1*09:01 (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-C*01:02 and DRB1*09:01. 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.