Naltrexone improves liver-related parameters, decompensation in alcohol use disorder

Key takeaways:

• At 12 months, 7.1% of patients with AUD and cirrhosis in the naltrexone group vs. 28.6% in the placebo group had new-onset hepatic decompensation.
• Naltrexone also can maintain abstinence and reduce cravings.

BOSTON — Oral naltrexone 50 mg safely improved alcohol use-related parameters and decompensation, and also reduced cravings, over 1 year among patients with alcohol use disorder and compensated cirrhosis, according to a presenter.

“Naltrexone is a pure opioid receptor antagonist with good efficacy in noncirrhotics,” Mohit Kumar Varshney, MD, DM, addiction psychiatrist at the Alcohol Use Disorder Clinic at the Institute of Liver and Biliary Sciences, said at The Liver Meeting. “But because of concerns of hepatic toxicity, there is reluctance. The gap in the literature is that there is no effective FDA-approved drug for cirrhosis, there is reluctance on the part of both patient and physicians and there was no double-blind study on naltrexone.”

Data previously presented at EASL Congress showed naltrexone achieved abstinence, reduced relapse and improved alcohol craving scores at 3 months among patients with alcohol-related cirrhosis.

Following up on these results, Varshney and colleagues evaluated naltrexone’s role in ongoing alcohol intake among patients with alcohol use disorder and compensated cirrhosis, as well as hepatic decompensation events after 12 weeks of naltrexone therapy. Researchers also studied abstinence, reduction in cravings, adverse events and changes in liver function parameters at 12 months.

Among 100 enrolled patients with cirrhosis and active alcohol consumption in the past 30 days, 96 were randomized to oral naltrexone (n = 48) or placebo (n = 48) for 12 weeks. Of those, 28 participants in each group completed 12 months of follow-up. Patients self-reported abstinence, lapses and cravings during the study period, with corroboration of family members.

Varshney noted similar baseline characteristics between treatment and placebo groups, including gamma-glutamyl transferase ([GGT] 470 IU/L vs. 457 IU/L, respectively) and Child-Turcotte-Pugh ([CTP] 6.1 vs. 6.4), MELD (13.6 vs. 12.2) and Alcohol Use Disorders Identification Test ([AUDIT] 22.2 vs. 21.2) scores.

Results showed 7.1% of patients in the naltrexone group had new-onset decompensation over 12 months compared with 28.6% in the placebo group (adjusted OR = 4.38; 95% CI, 2.9-41.69). Further, patients receiving naltrexone had “significant reductions” in CTP (–2.64 vs. –0.65) and MELD scores (–3.07 vs. –1.07), as well as total bilirubin (–0.97 vs. –0.52), INR (–0.37 vs. –0.22) and serum GGT (–127.23 IU/L vs. – 76.89 IU/L) compared with placebo.

The proportion of patients abstinent at 12 months was significantly higher in the naltrexone group vs. placebo, and craving measures were significantly lower with treatment. Varshney noted that the anti-craving effect of naltrexone was significant at 6 months, with a change in obsessive compulsive drinking scales of –9.85 vs. –5.7; however, the effect plateaued at 12 months (–9.96 vs. –5.48).

Adverse events were comparable between groups.

“Oral 50 mg naltrexone was safe with no significant adverse effects in compensated liver disease patients for AUD management,” Varshney concluded. “Naltrexone can maintain abstinence and reduce craving, and abstinence further reduces decompensation events over 1 year.”