Impact of Occult Hepatitis B Virus Infection in Hematopoietic Stem Cell Transplantation.

Using sensitive PCR assays, lower titers of hepatitis B virus (HBV) DNA has been detected in surface antigen (HBsAg)-negative patients, i.e., occult HBV infection, especially for those from HBV-endemic area. The pathogenic role of occult HBV infection has been studied in patients with HIV and HCV infection; however, its impact on hematopoietic stem cell transplantation (HSCT) is not understood at present. To examine the prevalence of occult HBV infection and resulting hepatic events through the course of HSCT, allogeneic HSCT recipients (and their donors) who were negative to HCV infection and HBsAg-negative before transplantation and had an at least 12 months of follow-up after transplantation were enrolled for the study, with serial follow up of serum HBV-DNA, HBV serology, and liver function tests through the course of HSCT. Nested PCR with 3 independent sets of primers were used to detect pre-S/S, precore/core and X viral regions of HBV as previously described, and those reactive by at least two of the three PCR assays were considered to have occult HBV infected. The impact of pre-transplant occult HBV infection was evaluated in terms of post-transplant HBV infection after transplantation. Between 1995 and 2004, 60 HBsAg-negative pairs of allogeneic HSCT recipients and donors were enrolled, with the characteristics of recipients: median age of 30 years (9–59), F/M=20/40, diagnosis including 18 AML, 12 ALL, 18 CML, 4 NHL and 8 SAA, graft including 28 BM and 32 PBSC, and preparative regimens including 44 myeloablative (BUCY and CYTBI) and 16 nonmyeloablative (fludarabine, busulfan and ATG). At transplant, total 6 recipients (10%, 6/60) and 2 donors (3%, 2/60) in different transplant pairs were found to occult HBV infection as defined. With a median follow up of 28 months (from 12.5 to 72 months) after transplantation, three of those 6 recipients with pre-transplant occult HBV infection (of whom all their donors had no occult HBV infection) had HBsAg appearance after transplantation. Importantly, for those two HSCT in which only donors were found to have occult HBV infection, occult HBV was only transiently detected in their recipients immediately after transplantation with a paralleled and transient elevation of quantitative serum HBV-DNA, but there was no HBsAg appearance. For the other recipients who did not have pre-transplant occult HBV infection, three also had HBsAg appearance. In conclusion, the impact of occult HBV infection on HSCT is mainly derived from those existed in the recipients rather than those from the donors.