Liver transplantation-associated de novo hepatitis B virus infection: Application of molecular evolutionary analysis

Objective: De novo hepatitis B virus (HBV) infection after liver transplantation has recently been reported to be associated with donors without serum hepatitis B surface antigen (HbsAg) but with hepatitis B core antigen (anti-HBc). We elucidate the source of de novo HBV infection after liver transplantation by molecular evolutionary analysis. Methods: The serum sample was obtained from a recipient who underwent living related liver transplantation. He was negative for all HBV-related serum markers before the transplantation. The recipient became seropositive for HBsAg at 6 months after transplantation. The liver tissue was obtained from a donor who was seronegative for HBsAg, but positive for anti-HBs and anti-HBc. Results: HBV DNA was detected from the serum and liver tissue in a recipient and donor, respectively. A total of 5 clones each of small-S gene of HBV from the donor and recipient were sequenced. A phylogenetic tree analysis based on small-S gene revealed that all isolates derived from the recipient and donor were clustered together within a close range of evolutionary distances. These results indicated that HBV was transmitted by the liver graft from the donor. Conclusions: Molecular evolutionary analysis can be adopted for the study of the transmission route of viral infection via organ transplantation.