(149) Safety of Naltrexone for Alcohol Use Disorder Treatment in Liver Transplant Recipients

Background & Introduction: Naltrexone is an FDA approved oral medication used to treat alcohol use disorder (AUD), with an injectable (IM) long-term option available. Data on safety of Naltrexone in liver transplant (LT) recipients is limited. Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation in the US. Many patients undergo early transplantation before a significant history of sobriety can be established, and relapse is common. These patients often warrant treatment in the post-transplant setting, but there are concerns regarding potential hepatotoxicity from naltrexone in fresh LT recipients. There is pressing need for safety data in this patient population. The aim of this study was to assess the safety of naltrexone for treatment of AUD in liver transplant recipients.

Methods: This is a single-center retrospective cohort of LT recipients who were prescribed naltrexone in a multi-disciplinary post-transplant clinic, co-managed by hepatology, addiction medicine, and pharmacy, between January 2023 to December 2025. Inclusion criteria included patients who reported taking naltrexone at follow-up after prescription. Documentation in provider notes and pharmacy data was used to confirm compliance. A minimum 3-months of continued naltrexone therapy with clinic follow-up and associated laboratory testing was required. Adverse events (AEs) were assessed during follow up visits and included reported side effects and liver test abnormalities. Discontinuation of therapy due to AEs were recorded.

Results: A total of 83 LT patients were pulled from the UCLA database who had been prescribed naltrexone. Of those, 32 patients met the inclusion criteria of at least 3-months of continued naltrexone therapy with appropriate follow up. The mean age of the cohort was 51 years old, with 17 (53%) female patients. The ethnic breakup included 17 (53%) Hispanic, 9 (28%) White, 4 (12%) Black, and 2 (6%) Asian. The most common primary etiology for LT was ALD (30, 93%), with comorbidities that included HCC (2), HBV (2), DILI (1), Diabetes (1), A1AT (1), and NASH (1). Acute liver failure secondary to a Tylenol overdose and cryptogenic cirrhosis as the other etiologies for the last two patients. 24 (75%) of patients met the criteria for severe AUD at the time of initial naltrexone prescription, while others were moderate or mild. The median duration of therapy was 8 months, with 14 (44%) of patients transitioning to IM naltrexone. There were 24 (75%) patients still on naltrexone therapy at the end of the study. The most common AE was elevated liver enzymes in 7 (22%) patients, with 5-mild and 2-moderate episodes. All elevated liver enzymes resolved without discontinuation of naltrexone and had other etiologies identified. Nausea (5 patients, 16%) was the second most common AE, followed by 1 reported instance of vomiting, somnolence, depression, decreased appetite, and heartburn each. 3 patients stopped naltrexone due to AEs in our cohort.

Conclusion & Discussion: Our cohort provides preliminary safety data on naltrexone use for AUD in liver transplant recipients, with low incidence of AEs, similar to non-transplant patient population. Further studies are needed to assess naltrexone’s efficacy in LT recipients. Our data suggests expansion of AUD pharmacotherapy to LT recipients is safe and may ideally be completed in a multi-disciplinary setting with co-management with hepatology and addiction medicine.

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Ayyala D, Bottyan T, Tien C, et al. Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease. Hepatology Communications. 2022;6(12):3433-3442. doi:10.1002/hep4.2080
Bolton M, Hodkinson A, Boda S, et al. Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. BMC Medicine. 2019;17(1):10. doi:10.1186/s12916-018-1242-0