CLINICOPATHOLOGICAL CRITERIA FOR MULTICENTRICITY OF HEPATOCELLULAR-CARCINOMA AND RISK-FACTORS FOR SUCH CARCINOGENESIS

Multicentric occurrence is an important characteristic of hepatocellul ar carcinoma. We evaluated clinicopathological criteria for multicentr ic hepatocellular carcinoma and identified risk factors for such carci nogenesis. Subjects were 251 consecutive patients undergoing liver res ection for hepatocellular carcinoma. One kind of multicentric hepatoce llular carcinoma had at least one tumor consisting of well-differentia ted hepatocellular carcinoma, together with moderately or poorly diffe rentiated hepatocellular carcinoma located in a separate region. The o ther kind had an area of well-differentiated component around hepatoce llular carcinoma with less differentiation in all occurrences. The out come of patients with tumors classified in this way was studied. Univa riate and multivariate analyses were done to identify risk factors for multicentric hepatocellular carcinoma. The cumulative survival rate w as significantly higher in patients with multicentric hepatocellular c arcinoma than in patients with hepatocellular carcinoma associated wit h intrahepatic metastasis. Analysis by Cox's proportional hazard model showed that multicentricity was not a factor in the outcome. The risk of multicentric occurrence increases with progression of chronic live r disease. Univariate analysis showed hepatitis C virus marker and hep atitis B core antibody to be risk factors. By multivariate analysis, t he odds ratio for multicentric occurrence in patients infected with he patitis C virus and with serum hepatitis B virus core antibody compare d with patients without either hepatitis C virus or hepatitis B virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.3 0. These criteria for multicentric hepatocellular carcinoma seem to be clinically useful. Hepatitis C virus infection with or without former infection by hepatitis B virus is a strong risk factor for multicentr ic hepatocarcinogenesis.