Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss

Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. We performed spatial transcriptomics to investigate the intrahepatic cell heterogeneity and the spatial distribution of transcriptionally active HBV integration events in different phases of chronic HBV infection. Our analysis revealed that transcriptionally active HBV integration occurred in chronically HBV-infected patients in different phases, including those patients with HBsAg loss, and antiviral treatment was associated with a decreased number and extent of viral integrations. Liver biopsies from 18 patients with chronic HBV infection were used for spatial transcriptomics sequencing. EP1-4 were HBeAg-positive patients, EN1-5 were HBeAg-negative patients, OT1-6 were on-treatment patients, SL1-3 were patients with HBsAg loss (SL).