title: Risk factors for grade 3-4 liver enzyme elevation in HIV and hepatitis C coinfected patients on combination antiretroviral therapy.
abstract: Although coinfection with hepatitis C (HCV) is an established risk factor for hepatotoxicity in HIV-positive patients receiving combination antiretroviral therapy (cART), specific variables that may be predictive of severe hepatotoxicity among co-infected patients receiving cART remain poorly defined. A retrospective cohort study of HIV/HCV coinfected adults from two HIV treatment centers covering the period between December 1998 and December 2003 was conducted to address this question. The primary endpoint of the study was the occurrence of grade 3 or 4 elevation of serum alanine aminotransferase (ALT) during follow-up and the primary predictors of interest were specific antiretrovirals. One hundred five coinfected patients receiving cART for a median of 70 months (interquartile range [IQR], 37, 83) were included in the analysis. Twenty-three (22%) patients developed a grade 3 or 4 increase in serum ALT at least once in follow-up. In univariate analysis, current receipt of lopinavir/ritonavir (LPV/r) (odds ratio [OR] 3.09, 95% confidence interval [CI] 1.14-8.34, p = 0.03), baseline ALT (OR 1.01, 95% CI 1.00-1.02, p = 0.004), and current use of boosting ritonavir (OR 2.84, 95% CI 1.16-7.00, p = 0.02) were significantly associated with a grade 3 or 4 increase in serum ALT, although most patients receiving boosting ritonavir were on lopinavir/ritonavir based regimens. Patients receiving LPV/r had been previously exposed to significantly more antiretrovirals (p < 0.0001), protease inhibitors (p < 0.0001), and nucleoside analogues (p = 0.0009) compared to the rest of the cohort. Further research to better clarify risk factors for hepatotoxicity in coinfected patients is warranted given the challenges in treating this population.
authors.affiliation: Maple Leaf Medical Clinic, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Chihrin
authors.forename: T
authors.initials: T
authors.lastname: Antoniou
authors.forename: J
authors.initials: J
authors.lastname: Raboud
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.forename: V
authors.initials: V
authors.lastname: Govan
authors.forename: D
authors.initials: D
authors.lastname: Fletcher
authors.forename: A
authors.initials: A
authors.lastname: Rachlis
authors.forename: C
authors.initials: C
authors.lastname: Kovacs
authors.forename: F
authors.initials: F
authors.lastname: Crouzat
authors.forename: D
authors.initials: D
authors.lastname: Tilley
authors.forename: B
authors.initials: B
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: Saskin
authors.forename: M R
authors.initials: MR
authors.lastname: Loutfy
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology; D006526:Hepatitis C / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D044966:Anti-Retroviral Agents; D000410:Alanine Transaminase