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Background:  Chronic hepatitis C follows an accelerated course in HIV infection. The reasons for this altered natural history are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. An enhanced hepatocyte apoptosis could be related with the faster progression of chronic hepatitis C in HIV-infected patients. Therefore, we compared the expression of Fas on hepatocytes and hepatocyte irreversible apoptosis between patients with chronic hepatitis C with and without HIV infection.

Methods:  Fas-immunostained hepatocytes were semiquantified and apoptotic hepatocytes, detected by staining of caspase-cleaved cytokeratin 18 filaments, were counted across the entire section of liver biopsy from patients with HCV infection with and without HIV coinfection.

Results:  We included in the study 134 patients with HIV/HCV co-infection and 100 patients with HCV infection. HIV infection was associated both with diffuse distribution of Fas-stained hepatocytes (Adjusted OR  [AOR] 7.4, 95% confidence interval [95% CI] 3.8 to 14.4) and with apoptotic hepatocyte counts/mm² above the median (AOR 2.5, 95%CI 1.5 to 4.5). Among HIV-infected patients, nadir CD4⁺ cell counts ≤ 200/mL was associated with Fas expression (AOR 2.9, 95% CI 1.3 to 6.8) and hepatocyte apoptosis (AOR 2.3, 95% CI 1.1 to 4.9). ART was associated with neither hepatocyte Fas expression nor apoptosis.

Conclusions:  HIV/HCV-co-infected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than HCV-mono-infected patients. On the other side, the nadir CD4⁺ cell counts is associated with hepatocyte Fas expression and apoptosis in coinfected patients.

Keywords: hepatitis C; hepatocyte apoptosis; liver fibrosis