Viral Genetics of De Novo Hepatitis B Virus Reactivation triggered by Immunosuppressive Condition. Hepatitis B virus

AbstractBackground & Aims: Individuals negative for hepatitis B virus (HBV) surface antigen (HBsAg) but positive for antibodies against the hepatitis B core antigen (HBc) are at risk of de novo HBV reactivation under immunosuppressive conditions. We investigated clinical features and viral genetics in patients with de novo HBV reactivation triggered by chemotherapy or immunosuppressive therapy.MethodsClinical courses of 14 individuals originally HBsAg-negative and anti-HBc-positive that experienced HBV reactivation were examined. Ultra-deep sequencing analysis of the entire HBV genome was conducted. Viral genetics were compared with individuals containing reactivated viruses that were initially HBsAg-positive. Prevalence of the G1896A variant in latently infected livers was determined among 44 healthy individuals that were HBsAg-negative and anti-HBc-positive.ResultsIn 14 cases, de novo 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 de novo HBV reactivation cases compared with that in individuals initially positive for HBsAg. The de novo reactivated viruses were almost exclusively the wild-type G1896 or G1896A variant. The G1896A variant was detected in 43% (6/14) of cases, including two cases with fatal liver failure. The G1896A variant was observed in the liver of 11% (5/44) of individuals with occult HBV infection.ConclusionsDe novo HBV reactivation is characterized by low genetic heterogeneity, with the wild-type G1896 or G1896A variant prevalent. Predominant occult HBV infection with the G1896A variant might contribute to the pathophysiology of the development of de novo hepatitis B.