Gopalakrishna 2025: liver injury from alcohol medicines in a US registry

What they tested

The Drug-Induced Liver Injury Network (DILIN) is a US study that collects cases of liver damage caused by medicines. Researchers pulled every high-confidence case (rated definite, highly likely or probable) caused by a medicine for alcohol use disorder between 2004 and 2024.

They looked at each person's background, lab results and health 6 months later. For disulfiram cases, they also compared immune-system gene types (HLA alleles) with people whose liver injury came from other drugs.

What they found

Of the 13 cases from alcohol medicines, 11 were disulfiram, 1 was naltrexone and 1 was baclofen. None was caused by acamprosate. The median age was 45, 77% were women, and all had hepatocellular injury, damage to the liver cells themselves.

Disulfiram injury showed up after a median of 34 days. Eight patients developed jaundice, and there were 3 fatal or near-fatal cases: 2 liver transplants and 1 death from liver disease. Five (71%) of the people with severe or fatal disulfiram injury already had liver disease.

Liver injury from naltrexone and baclofen was mild and self-limited, meaning it cleared up on its own, with no lasting liver damage. The site's liver tests guide notes that the one naltrexone case was a woman taking low-dose naltrexone who already had fatty liver.

Two gene types, HLA-C*01:02 and DRB1*09:01, were more common in people with disulfiram injury than in people with liver injury from other drugs (odds ratios 6.29 and 10.16).

Limits

• A registry only captures cases that doctors recognize and refer, so it can't give a rate of liver injury per person taking each drug.
• With a single naltrexone case, the registry can't describe what naltrexone liver injury typically looks like.

What it means if you're considering naltrexone

For someone weighing alcohol medicines, this registry puts naltrexone far behind disulfiram as a cause of serious liver injury. It supports the authors' view that liver injury from these medicines is less frequent than concerns suggest, though it can't replace liver monitoring a prescriber may advise.