Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

Abstract

Background. Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. Aim. To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. Materials. Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. Methods. Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). Results. Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender, higher transaminase levels, hepatitis C virus, higher histological grading and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. Conclusions. Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity.