title: Hepatic Safety of Buprenorphine in HIV-Infected and Uninfected Patients With Opioid Use Disorder: The Role of HCV-Infection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. Electronic address: jeanette.tetrault@yale.edu.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Tetrault
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; VA Connecticut Health Care System, West Haven, CT.
authors.forename: Janet P
authors.initials: JP
authors.lastname: Tate
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: E Jennifer
authors.initials: EJ
authors.lastname: Edelman
authors.affiliation: VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, PA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gordon
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lo Re
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: VA Medical Center, Atlanta, GA; Emory University School of Medicine, Atlanta, GA.
authors.forename: David
authors.initials: D
authors.lastname: Rimland
authors.affiliation: VA Connecticut Health Care System, West Haven, CT; Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
authors.forename: Joseph
authors.initials: J
authors.lastname: Goulet
authors.affiliation: Center for Health Services Research, Institute for Health, Rutgers University.
authors.forename: Stephen
authors.initials: S
authors.lastname: Crystal
authors.affiliation: Center for Interdisciplinary Research on AIDS, Yale University School of Public Health, New Haven, CT.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gaither
authors.affiliation: VA Medical Center Washington DC; George Washington University School of Medicine and Health Sciences, Washington, DC.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Gibert
authors.affiliation: Michael E. DeBakey VA Medical Center and Baylor College School of Medicine, Houston, TX.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rodriguez-Barradas
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Fiellin
authors.affiliation: National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD.
authors.forename: Kendall
authors.initials: K
authors.lastname: Bryant
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; VA Connecticut Health Care System, West Haven, CT; Center for Interdisciplinary Research on AIDS, Yale University School of Public Health, New Haven, CT.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Center for Interdisciplinary Research on AIDS, Yale University School of Public Health, New Haven, CT.
authors.forename: David A
authors.initials: DA
authors.lastname: Fiellin
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology*; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D012307:Risk Factors
chemical_list: D002047:Buprenorphine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Buprenorphine; Drug induced liver injury; HIV; Hepatitis C