Safety of naltrexone in patients with cirrhosis

Abstract

BackgroundTreatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns for drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis. MethodsThis was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine transaminase or alkaline phosphatase elevations to more than 2 times or 5 times the upper limit of normal, respectively. The Roussel Uclaf Causality Assessment Method (RUCAM) was used to determine if DILI occurred. ResultsA total of 3285 patients with cirrhosis were initiated on naltrexone and 2940 of these had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as “DILI excluded” and 32 (52%) were classified as “DILI unlikely”. No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone. ConclusionsNaltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis. Impact and ImplicationsNaltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns for hepatotoxicity. This retrospective study shows no drug induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.