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Pretreatment of Chronic Active Hepatitis C in Patients Coinfected With HIV and Hepatitis C Virus Reduces the Hepatotoxicity Associated With Subsequent Antiretroviral Therapy

Uberti-Foppa Caterina; De Bona, Anna; Morsica, Giulia; Galli, Laura; Gallotta, Giulia; Boeri, Enzo; Lazzarin, Adriano
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2003

Summary:Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral-related hepatotoxicity, but little is known about the frequency of severe liver toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated). The aim of this prospective study of 105 patients was to compare the incidence of progression to severe antiretroviral-related liver toxicity in 66 patients pretreated (36 with interferon-α [IFNα], 30 with IFNα plus ribavirin), and 39 patients not pretreated. The subjects could choose whether to receive anti-HCV therapy. Severe liver toxicity was defined as alanine aminotransferase (ALT) level ≥5-times the upper limit of normal in patients with normal baseline levels and ≥3.5-times in those with increased baseline levels. The authors also estimated the hepatotoxicity-related risk of discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39 untreated patients (24month survival: 94% ± 2.9% vs. 85% ± 5.8%). After adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of patients not pretreated), and previous anti-HCV therapy, the risk of discontinuing anti-HIV treatment was significantly higher in the anti-HCV untreated patients (RR = 10.4; 95% CI: 1.6-66; p = .0127) and in those with increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p = .0005). The authors' data suggest that previous treatment of chronic active HCV is an independent factor associated with a decrease of severe liver toxicity as the result of a subsequent antiretroviral regimen. The authors also confirm that the baseline level of ALT is an important prognostic factor for increased liver damage during antiretroviral therapy.

Address correspondence and reprint requests to Caterina Uberti-Foppa, Infectious Diseases Department, Vita-Salute San Raffaele University, Via Stamira D'Ancona 20, 20127 Milano, Italy. E-mail:

Presented in part at the Eighth European Conference on Clinical Aspects and Treatment of HIV-1 Infection, Athens, October 28-30, 2001.

Manuscript received November 20, 2002; accepted March 5, 2003.

© 2003 Lippincott Williams & Wilkins, Inc.