Svicher V Salpini R, Piermatteo L, et al. - This study was undertaken to investigate the intrahepatic hepatitis B virus (HBV) reservoir, the occurrence of HBV DNA integration, and its effect on the hepatocyte transcriptome in hepatitis B ‘e’ antigen (HBeAg)-negative chronic hepatitis B (CHB). Researchers examined liver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25), and high (n=47) serum HBV DNA. They assessed covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) by quantitative PCR, whole-exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was assessed by digital droplet PCR. The data exhibited that HBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localizing in genes involved in carcinogenesis and altering the hepatocyte transcriptome.