Relationship of hepatocellular carcinogenesis with precore mutant virus and serum hepatitis B virus DNA concentration: A longitudinal analysis of patients with cirrhosis

Abstract

In order to elucidate the influence of hepatitis B virus on the hepatocellular carcinogenesis in cirrhotic liver, quantitative analysis of precore region of hepatitis B virus was sequentially carried out. Among 191 patients who were diagnosed with cirrhosis in our hospital between 1974 and 1992 and had received no anti-viral therapy, 52 patients were selected from the following three patient groups: group A, 17 patients with liver cancer development within 5 years after the diagnosis of cirrhosis; group B, 12 patients with cancer development between 5 and 10 years after the diagnosis; and group C, 23 patients without cancer development during the observation period of 10 years or more. In group A, 16 out of 17 patients steadily showed a large amount of precore mutant virus with a high concentration of 10 4 copy/ml or more throughout the observation period. In group B, precore mutant virus was persistently high in eight of 12 patients. The other four patients showed an increase in mutant virus until the appearance of HCC, from a low concentration of less than 10 4 copy/ml to a high concentration. Of 23 patients in group C, no mutant virus was detected throughout the 10 year observation period in 11 patients and a complete disappearance of the mutant virus was found during the observation period in seven patients. Mutant virus was detected at least once in the clinical courses in the five remaining of group C. The amount of precore mutant virus at the endpoint of observation was significantly associated with HCC development (28/29 vs. 5/23, P<0.000001). To conclude therefore, appearance or persistence of precore mutant HBV suggested an increased risk of HCC development and its sequential analysis could be very useful in prediction and early detection of small HCC.