Another reason not to withhold naltrexone from people with alcohol-related cirrhosis
STUDY: Alla M et al, Liver International 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Independent
Background
Naltrexone has a warning about hepatotoxicity, something seen in high doses, but it also helps people stop drinking. This trial clarifies its role in patients with severe liver disease (cirrhosis) from alcohol.
The Study
- 100 men with compensated alcohol-associated cirrhosis and alcohol use disorder, randomized to naltrexone 50 mg/day or placebo for 12 weeks, plus brief psychosocial support in both arms.
- Primary outcome: abstinence at 12 weeks; secondary outcomes included craving, lapses, relapse, and liver safety through 24 weeks.
Results
Abstinence at 12 weeks was 64% with naltrexone versus 22% with placebo (OR 10.86, p<0.001). Naltrexone lowered craving scores and roughly halved lapse rates (28% vs 54% at 3 months); fewer heavy-drinking relapses trended in its favor but weren’t significant.
Side Effects
Adverse events (nausea, sedation, gastritis) were infrequent and similar between groups. No patient had hepatic decompensation or an AST/ALT rise beyond 5 times normal from the drug; two naltrexone patients developed jaundice, tied to ongoing drinking, not drug-induced injury.
Limitations
All participants were men at a single center. Decompensated cirrhosis was excluded, follow-up was 6 months, and alcohol use relied mainly on self-report.
Practice Implications
- This is the first randomized evidence that standard-dose naltrexone is safe and effective in compensated cirrhosis, challenging the practice of withholding it over old, high-dose hepatotoxicity data.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
