Thompson 2024: naltrexone and liver injury in veterans with cirrhosis

What they tested

Researchers searched a Veterans Affairs database called VOCAL for people with cirrhosis, serious scarring of the liver, who started naltrexone after their diagnosis and had liver enzymes checked within 3 months. That is the period when drug-caused liver injury is most likely to show up.

When someone's ALT, a liver enzyme, rose above 2 times the upper limit of normal, or their alkaline phosphatase rose above 5 times, the team reviewed the chart. They used a standard scoring system called RUCAM to judge how likely it was that naltrexone caused the rise.

What they found

Of 3,285 people who started naltrexone, 2,940 had liver tests during the high-risk period. Only 2% of them had enzyme rises large enough to prompt a chart review.

Of those reviewed, 30 (48%) were rated as drug-induced liver injury excluded and 32 (52%) as drug-induced liver injury unlikely. No one was rated as possible, probable or highly probable liver injury from the drug.

No deaths or new decompensations were attributed to naltrexone. The authors concluded that it appears safe in both compensated and decompensated cirrhosis.

Limits

• It looked back at medical records. No one was randomly assigned to naltrexone or a placebo, so it can show what happened to people who took it but not compare them with similar people who didn't.
• Everyone was a US veteran, a group that is mostly men, so the results may not carry over fully to women.
• People who started naltrexone but weren't tested in the 3-month window couldn't be assessed for liver injury.

What it means if you're considering naltrexone

Doctors have often held back naltrexone from people with liver disease because of older worries about liver damage. In this large group of veterans with cirrhosis, no case of liver injury was judged likely to be caused by naltrexone, which weakens the case for ruling it out on liver grounds alone.

Data for the most severe liver disease are still thin, as the site's liver tests guide notes, so this study is reassuring rather than the final word for every person with cirrhosis.