Patterns of Hepatitis B Virus DNA Integration in Liver Tissue of Children with Chronic Infections

Abstract

SummaryAlthough an integration of hepatitis B virus (HBV) DNA in children with chronic HBV infection has been documented at early phases of the disease, the incidence of this process is not known. Therefore we examined nine liver DNA specimens from chronic HBV carriers ages 5‐14 years and one sample from a neonate delivered of a carrier mother, in order to determine the HBV DNA patterns of these patients at different ages and phases of chronic infection. The integrated HBV DNA was detected by Southern blot hybridization and analyzed by molecular cloning. Southern blot showed a smear pattern of HBV DNA integration in four of six chronic hepatitis patients (ages 5‐14), as well as in one asymptomatic carrier (age 12). Multiple and random integrations occurred during chronic infections in childhood. The neonate did not, however, show signs of any integrations, suggesting that integration starts after HBV multiplication. A band pattern that suggested clonal growth of integrated liver cells was found in a chronic active hepatitis patient (age 9) and in one of two hepatocellular carcinoma patients (age 11). Molecular cloning in two cases with chronic active hepatitis showed that the HBV genome structure was preserved in five of six HBV DNA inserts. Our findings confirm that HBV DNA integration can occur at early stages of chronic HBV infection. In Japanese children, the process of integration seems to be common regardless of HBeAg/anti‐HBe status. Thus, repetitive liver biopsies in chronic hepatitis B are useful not only to provide prognostic information referring to the histological progress of the disease but also to reflect the change of HBV DNA pattern in liver tissue during follow‐up.