title: Severe transaminitis after interferon-ribavirin therapy in HIV/HCV-coinfected patients: influence of a sustained HCV response.
abstract: Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis.
authors.affiliation: Groupe Hospitalier Universitaire Est, INSERM U 707, Université Pierre et Marie Curie, UMR-S 707, UPMC-Paris 6, Paris, France. firouze.bani-sadr@tnn.ap-hop-paris.fr
authors.forename: F
authors.initials: F
authors.lastname: Bani-Sadr
authors.forename: E
authors.initials: E
authors.lastname: Krastinova
authors.forename: D
authors.initials: D
authors.lastname: Fromentin
authors.forename: L
authors.initials: L
authors.lastname: Piroth
authors.forename: E
authors.initials: E
authors.lastname: Rosenthal
authors.forename: Y
authors.initials: Y
authors.lastname: Quertainmont
authors.forename: C
authors.initials: C
authors.lastname: Perronne
authors.forename: P
authors.initials: P
authors.lastname: Cacoub
authors.forename: S
authors.initials: S
authors.lastname: Pol
authors.forename: F
authors.initials: F
authors.lastname: Carrat
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001219:Aspartate Aminotransferases / Q000097:blood*; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D012254:Ribavirin; D007372:Interferons; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase