Predictors of hepatocyte proliferative activity in chronic hepatitis B and C vs. steatohepatitis as assessed by the monoclonal antibody MIB1-Ki-67

Abstract 

Background and study aims

Chronic hepatitis is characterised by increased regenerative cell proliferation, a process that makes cells more susceptible to gene mutations and development of hepatocellular carcinoma (HCC). Evaluation of the proliferative index could be a useful tool for identifying patients at risk for HCC. The current study was planned to evaluate hepatocyte proliferation in predominant causes of chronic liver disease in an attempt to investigate predictors of proliferation.

Patients and methods

This study included 84 patients with chronic liver diseases, and they were classified into three groups: chronic hepatitis C (50 patients), non-alcoholic steatohepatitis (NASH) (20 patients) and chronic hepatitis B (14 patients). All cases were investigated by liver function tests, polymerase chain reaction (PCR) hepatitis C virus (HCV) and hepatitis B virus (HBV), routine abdominal ultrasound and liver biopsy with detection of the proliferative index using the monoclonal antibody MIBI-Ki-67.

Results

The proliferative index was significantly higher in the chronic hepatitis C group than in the chronic hepatitis B group (P value=0.007). There were significant correlations of the Ki-67 index in both zone 1 and zones 2 and 3 with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and histological activity index (HAI) score. Using the multiple regression analysis on the variables affecting proliferation, it was found that predictors of zone 1 proliferation were the following variables: ALT, age, AST and aetiological factor, in that order.

Conclusion

HCV aetiology had significantly higher proliferation index, whereas NASH had the least. Increased HAI score is associated with higher proliferative index in either zone 1 or zones 2 and 3. Predictors of proliferation index in zone 1 were ALT, age, AST and aetiological factor.

Keywords: Predictors of proliferative activity, HCV, HBV, NASH, Ki-67