Genomic Integration of Hepatitis B Virus Into Human Hepatocytes in Early Childhood Cirrhosis

Hepatitis B virus (HBV) remains a major global health problem. HBV DNA can be integrated into the human chromosomes. The integration in young cirrhotic chronic hepatitis B children has not been explored. This study aims to investigate HBV DNA integration in early childhood cirrhosis. Biopsy liver specimens from cirrhotic and matched non-cirrhotic chronic hepatitis B children were collected. HBV DNA integration was detected through targeted HBV DNA fragment capture sequencing. Twenty cirrhotic and 20 non-cirrhotic children with chronic hepatitis B were included in the study. The cirrhotic group included 14 males and 6 females, and the non-cirrhotic group included 13 males and 7 females. Compared to non-cirrhotic children, cirrhotic children had lower serum HBsAg quantification (p = 0.001). The median number of HBV integrants in the cirrhotic group was 59 and that in the non-cirrhotic group was 98. No significant difference existed between the two groups (p = 0.529). In the multivariate linear regression analysis, serum HBV DNA level was correlated with the number of HBV integrants (p < 0.001, R2 = 0.322). Six differential intragenic high-frequency viral integration sites in cirrhotic children were revealed, all of which have protein-coding functions. Several frequently integrated genes were observed in early childhood cirrhosis. Detailed associations between genetic alterations induced by HBV integration and early childhood cirrhosis need further exploration.