Extended Lamivudine Therapy against Hepatitis B Virus Infection in Hematopoietic Stem Cell Transplant Recipients

YMDD mutation–associated breakthrough during extended lamivudine therapy. A 40-year-old HBsAg-positive man with acute myeloid leukemia (patient 1 in ), who received lamivudine between 1 week before transplantation and 73 weeks after transplantation, had an HBV DNA (•) breakthrough and an ALT (○) increase 56 weeks after transplantation (ie, 57 weeks of lamivudine therapy). With an amplification-restriction detection method [29], PCR products of wild-type (YMDD) and mutant-type (YVDD) viruses were 111 and 86 base pairs (bp), respectively. In the lane below, of gel electrophoresis, the mutation in fact preexisted in the mixture of wild-type and mutant-type viral population before lamivudine therapy (14 weeks before transplantation) and became dominant during therapy (72 weeks after transplantation). After discontinuation of therapy, the mutant type was soon taken over by the wild type (85 weeks after transplantation). Shaded block, period of lamivudine therapy; ○, value of ALT (IU/L); •, value of log₁₀ HBV DNA (copies per milliliter).

Late viral recurrence with icteric hepatitis manifested 31 weeks after discontinuation of lamivudine therapy. A 45-year-old HBsAg-positive woman with non-Hodgkin lymphoma (patient 4 in ), who had a previous episode of HBV reactivation hepatitis during pretransplantation chemotherapy (arrow), had received lamivudine since 20 weeks before transplantation to allow completion of subsequent chemotherapy and autologous HSCT. Therapy was discontinued 26 weeks after transplantation; however, viral recurrence with icteric hepatitis occurred 31 weeks later, with a surge of serum HBV DNA levels and the appearance of serum HBeAg and anti-HBc IgM. Hepatitis was resolved after reinitiation of lamivudine therapy. ○, value of ALT (IU/L); •, value of log₁₀ HBV DNA (copies per milliliter).

Curve of cumulative hazards for HBV reactivation hepatitis after transplantation in HBsAg-positive HSCT recipients according to lamivudine therapy. Cox proportion hazards regression analysis adjusted by several independent factors showed that lamivudine therapy was the only statistically significant factor, with hazard ratio of 0.122 (with versus without lamivudine therapy; 95% confidence interval, 0.016-0.908; P = .040).