by
Jeanette M. Tetrault;
Janet P. Tate;
E. Jennifer Edelman;
Adam J. Gordon;
Vincent Lo Re;
Joseph K. Lim;
David Rimland;
Joseph Goulet;
Stephen Crystal;
Julie R. Gaither;
Cynthia L. Gibert;
Maria C. Rodriguez-Barradas;
Lynn E. Fiellin;
Kendall Bryant;
Amy C. Justice;
David A. Fiellin
Introduction: Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity. Materials and methods: We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI. Results: Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 7.3, 95% CI 2.1–26.1, p = 0.002), HCV-infected (OR 4.9 95% CI 1.6–15.2, p = 0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1–22.2, p = 0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p = 0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p = 0.002); 8 experienced DILI, 4/202 HIV-infected and 4/204 uninfected (p = 0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status. Conclusions: Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring.