Histological features of cirrhosis with hepatitis C virus for prediction of hepatocellular carcinoma development; A prospective study

The histological features of pre-neoplastic lesions in HCV-associated cirrh osis remain uncertain. The aim of this prospective study was to elucidate h istological features for predicting the development of hepatocellular carci noma (HCC). A cohort of 72 consecutive patients with hepatitis C-associated cirrhosis, which was diagnosed by histology investigated for development o f HCC. Seven histological features including small cell dysplasia (SCD) and large cell dysplasia (LCD) of liver cirrhosis were evaluated with regard t o the development of HCC. In addition, proliferation and apoptosis were inv estigated using immunohistochemistry by proliferating cell nuclear antigen and TUNEL method, respectively. At enrollment, SCD was observed in the biop sy specimens of 18 out of 72 (25.0%) patients and LCD was observed in 20 ou t of 72 (27.8%). Twenty eight out of 72 patients (38.9%) developed HCC duri ng a mean follow-up period of 72.4 months. Among the histological parameter s, SCD, active inflammation and complete nodule were statistically signific ant factors for the cumulative probability of developing HCC. However, LCD did not appear to be important for HCC development. In multivariate analysi s, SCD was the highest independent risk factor for HCC. Samples with SCD de monstrated a higher proliferative rate and a lower apoptotic rate than norm al hepatocytes or samples with LCD. These results indicate that SCD is a ma jor risk factor for HCC. Careful assessment of liver histology may be impor tant in order to predict HCC development in patients with HCV-related cirrh osis.