[ANRS HC 02 RIBAVIC: histo-pathological impact]

Anti-hepatitis C virus (HCV) therapy allows complete recovery of HCV infection (sustained virologic response). Reduction of necro-inflammation results usually in a stabilization then in a reduction of fibrosis and even of cirrhosis at least in patients with sustained virologic response. The randomised controlled RIBAVIC ANRS HC02 trial comparing the combination ribavirin-pegylated interferon-alpha2b versus ribavirine-standard interferon-alpha2b as first treatment in HIV-HCV co-infected patients allowed an analysis of 205 paired (pre- and post-treatment) biopsies using the Metavir and Ishak scores. A significant reduction was associated with sustained virologic response and non response with stabilization. There was no positive impact on fibrosis despite sustained virologic response and a deterioration in non responders. In multivariate analysis, didanosine and non response were significantly associated with fibrosis deterioration. The absence of fibrosis reversal in co-infected patients is related to virologic non response and probably to co-factors of fibrosis worsening, like the mitochondrial toxicity of antiretrovirals and especially of didanosine. In the RIBAVIC cohort (prospective followup of 383 co-infected HIV-HCV treated patients) with a median of 60 months, 21 patients (5 %) had a liver event: all were non responders and 20 had fibrosis score > or = F3. In multivariate analysis, factors associated with survival were virologic response to antiviral therapy, fibrosis score < F3 and baseline CD 4 count > 350/mL. These results emphasize the need of early therapeutic interventions to increase the rate of sustained virologic response and to decrease the rate of liver complications in the most severe patients.