Naltrexone tripled abstinence in compensated alcohol-associated cirrhosis without hepatic harm

The edition in brief

The finding most likely to change what you prescribe concerns a drug most hepatologists have been taught to avoid. Alcohol use disorder with cirrhosis carries high mortality and has no approved pharmacotherapy, largely because naltrexone's label has long carried hepatotoxicity warnings. NAL-CI randomised 100 patients with compensated alcohol-associated cirrhosis and DSM-5 alcohol use disorder to naltrexone 50 mg daily or placebo for twelve weeks, with standardised psychosocial support in both arms. Mean MELD was about 12.6. Point-prevalence abstinence at twelve weeks was 64% with naltrexone and 22% with placebo. Lapses fell from 54% to 28%, and craving scores dropped on both obsessive and compulsive subscales. On safety — the question that has kept this drug out of hepatology clinics — no patient developed decompensation attributable to study medication, and neither arm produced an AST or ALT rise above five times the upper limit of normal. Two negatives complete the day. In 813 patients where rectal NSAIDs are unavailable, acetate-buffered crystalloid did not beat lactated Ringer's for preventing post-ERCP pancreatitis, so Ringer's remains first line. And an antisense oligonucleotide for hepatitis B was discontinued after four of eight treated patients developed drug-induced liver injury — in a trial where single doses had been well tolerated by healthy volunteers.