Increased hepatocyte Fas expression and apoptosis in HIV and hepatitis C virus coinfection

Background. Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection. Methods. Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection. Results. One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/ HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes ( adjusted odds ratio [AOR], 7.4 [ 95% confidence interval {CI}, 3.8 - 14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5 - 4.5]). In HCV/ HIV-coinfected patients, CD4(+) cell nadir < 200 cells/mL was associated with both Fas expression (AOR, 2.9 [ 95% CI, 1.3 - 6.8]) and hepatocyte apoptosis ( AOR, 2.3 [ 95% CI, 1.1 - 4.9]). Conclusion. HCV/ HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4(+) cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.