Reactivation from occult HBV carrier status is characterized by low genetic heterogeneity with the wild-type or G1896A variant prevalence

Abstract

Individuals negative for hepatitis B surface antigen (HBsAg) but positive for antibodies to hepatitis B core antigen (anti-HBc) are at risk of hepatitis B virus (HBV) reactivation under immunosuppressive conditions. We investigated clinical features and viral genetics in patients with reactivation from occult HBV infection triggered by chemotherapy or immunosuppressive therapy. Clinical courses of 14 individuals originally HBsAg-negative but anti-HBc-positive that experienced HBV reactivation were examined. Ultra-deep sequencing analysis of the entire HBV genome in serum was conducted. Prevalence of the G1896A variant in latently infected livers was determined among 44 healthy individuals that were HBsAg-negative but anti-HBc-positive. In 14 cases, HBV reactivation occurred during (n=7) and after (n=7) termination of immunosuppressive therapy. Ultra-deep sequencing revealed that the genetic heterogeneity of reactivated HBV was significantly lower in patients with reactivation from occult HBV carrier status compared with that in patients from HBsAg carrier status. The reactivated viruses in each case were almost exclusively the wild-type G1896 or G1896A variant. The G1896A variant was detected in 42.9% (6/14) of cases, including two cases with fatal liver failure. The G1896A variant was observed in the liver tissue of 11.4% (5/44) of individuals with occult HBV infection. Reactivation from occult HBV infection is characterized by low genetic heterogeneity, with the wild-type G1896 or G1896A variant prevalent.