Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-bi otin nick-end labeling (TUNEL) we have evaluated and quantified apoptosis i n liver biopsy specimens from 61 patients with chronic hepatitis C. All pat ients had detectable apoptotic cells in the liver. Presence of increased ap optotic activity was confirmed in selected cases by electron microscopy and by DNA gel electrophoresis. The amount of liver cell apoptosis expressed a s apoptotic index, ranged between 0.01% to 0.54% and showed a positive corr elation with histological activity grading (P < .0005) and with the amount of infiltrating CD8-positive cells (P = .01). Apoptosis did not correlate w ith transaminase levels or with HCV load and genotype, These results suppor t the concept that immune-mediated apoptosis may play a role in the pathoge nesis of chronic hepatitis C and indicate that this type of reaction may oc cur in the absence of significant alanine transaminase (ALT) elevation, thu s explaining the lack of correlation between biochemical activity and liver histological damage.