Background of study: HIV-infected patients who have chronic hepatitis C virus (HCV) infection have 2.5 to 3 times the risk of a serious liver enzyme elevation after starting an anti-HIV regimen containing a protease inhibitor, compared with HIV-infected patients without hepatitis.
Objective: To assess the 2-year effects of interferon-alpha (IFN-α) + ribavirin therapy on chronic active hepatitis (CAH) C and on the liver tolerability of anti-HIV drugs in 70 HIV-positive patients with CAH treated or not with IFN-α + ribavirin.
Design: We took liver biopsies from 70 HIV-HCV coinfected candidates for two prospective studies on the efficacy of 6 MU thrice–weekly subcutaneous doses of IFN-α (Group A: 27 patients) or of 6 MU every other day + 800-1200 mg of ribavirin daily for six months (Group B:19 patients); the 24 refusers (Group C) were used as controls to evaluate the subsequent liver tolerability of anti-HIV drugs.
Results: At baseline ALT levels were 134+145 IU/L and CD4 counts 451+ 183 cells/µL. Twenty-two patients of group A and all subjects of group B started anti-HIV therapy after the end of the anti-HCV treatment with two nucleoside reverse transcriptase inhibitors (NRTIs : 11 of group A and 5 of group B), or with highly active antiretroviral therapy (2 NRTIs + 1 Protease Inhibitor= HAART: 11 of group A and 14 of B). Of the remaining five, one was lost of follow-up and four were not treated because of the absence of any indication. Eleven patients of group C started therapy with NRTIs, 12 with HAART, and one was not treated. Liver injury was classified based on changes relative to baseline (2.6-3.5 x baseline), bilirubin levels>5
g/L and or the development of clinical hepatic failure. ALT levels had returned to normal and serum HCV-RNA was no longer detectable at the end of therapy in seven patients (25.9%) of IFN-α group and in 12 (63%) of the combination therapy, but in only one (3.7%) of group A and in 6(31.5%) of group B six and 18 months later. During the 24-months of follow-up, 14 patients experienced liver toxicity: 3 of group A(2 HAART and 1 NRTIs), 3 from group B (2 HAART and 1 NRTIs) and 8 controls (6 HAART and 2 NRTIs). After adjusting for baseline CD4+ cell counts, ALT levels, histological grading and HCV-1 genotype (1 vs others), the risk of hepatotoxicity due to anti-HIV drugs was significantly higher in the untreated group (p< 0.001).
Conclusions: Our data indicate that in HIV-HCV coinfected subjects with CAH, anti-HIV drug-induced hepatotoxicity is significantly reduced (from 2 to 3 times) by anti-HCV pretreatment, even in absence of a long-term hepatitis C virological response.
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