HEPATOCYTE REGENERATION IN CHRONIC HEPATITIS-C AND INTERFERON TREATMENT - ANALYSIS OF IMMUNOHISTOLOGICAL IDENTIFICATION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA)

To evaluate the usefulness of proliferating cell nuclear antigen (PCNA ) immunostaining in the assessment of the efficacy of interferon (IFN) therapy in chronic hepatitis C, we investigated the proliferative act ivity of hepatocytes in 67 patients with chronic hepatitis C, using th is immunostaining method. The percentage of PCNA-positive hepatocytes was 2.4% in patients with chronic persistent hepatitis, 2.5% in those with chronic aggressive hepatitis 2A, and 3.9% in those with chronic a ggressive hepatitis 2B. The PCNA count increased with the progression of the liver disease. Patients were classified as complete, partial, a nd non-responders to IFN; the percentage of PCNA-positive hepatocytes before IFN therapy was 1.6% in the complete responders, 3.9% in the pa rtial responders, and 4.9% in the non-responders. There was a signific ant negative correlation between the percentage of PCNA-positive hepat ocytes and the response to IFN treatment. Thirty-two of 53 cases (60.4 %) in which the PCNA labeling index (LI) was less than 5.0 were comple te responders compared with 13 of 14 cases (92.9%) in which the PCNA L I was higher than 5.0, representing partial responders or non-responde rs (P < 0.001). Most complete responders had a low PCNA LI, irrespecti ve of HCV genotype. Our findings indicate that PCNA immunostaining is a simple and reliable index of cell proliferation in liver regeneratio n, and may be a useful predictor of the response to IFN treatment in c hronic hepatitis C.