Apoptotic cell death does not parallel other indicators of liver damage inchronic hepatitis C patients

The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclea r. Recent in vitro studies have suggested that the HCV core protein may dis rupt specific signalling pathways of apoptosis. This prompted us to study p atients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated w ith histological findings; and to investigate if apoptosis is related to th e histological activity of the disease. Twelve patients with chronic hepati tis C were included in the study. Liver histology was scored by using the h istological activity index (HAI) of Knodell et al. DNA fragmentation was as sessed in liver tissue by the terminal deoxynucleotidyl transferase-mediate d deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine metho ds were used to determine serum markers of liver disease. Bile acids were m easured in serum and liver by gas chromatography. Patients were placed, acc ording to their HAI score, into group A (3.8 +/- 0.3) or group B (7.8 +/- 0 .8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were sl ightly higher in serum and liver of patients in group A. Liver biopsies wit h low HAI scores showed an increased rate of apoptosis (18.0 +/- 4.0 apopto tic cells per field) compared to those with higher HAI scores (6.6 +/- 2.1, P < 0.05) or to controls (3.5 +/- 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apop totic response. The lower apoptotic rate in advanced liver disease may be a ssociated with the high incidence of hepatocellular dysplasia/neoplasia.