Extended lamivudine therapy against hepatitis B virus infection in hematopoietic stem cell transplant recipients.
Lamivudine has demonstrated efficacy in the treatment and prevention of hepatitis B virus (HBV) reactivation after hematopoietic stem cell transplantation (HSCT). However, most of these studies involved short durations of prophylaxis, so there is significant concern regarding lamivudine resistance in these patients. Between March 1984 and November 2002, 71 HBV surface antigen-positive HSCT recipients, including a subgroup of 16 who received pretransplantation lamivudine therapy, which was continued into the posttransplantation period to prevent reactivation hepatitis, were enrolled onto our study. The efficacy of lamivudine therapy was first evaluated for the subgroup of 16 patients in terms of treatment response, lamivudine resistance, and viral recurrence after discontinuation by using virologic assays. Efficacy was then evaluated for all patients in terms of the hazards of lamivudine therapy for reactivation hepatitis after transplantation. During a median lamivudine therapy period of 73 weeks (range, 19-153 weeks), the initial response showed a median reduction of 2.54 log10 in serum HBV DNA (-0.28 to 6.72 range). Lamivudine-resistant mutations were detected in 10 (63%) of 16 patients during therapy, and 1 (12%) of 16 patients finally developed a viral breakthrough. At a median follow-up of 30 months after discontinuation, 3 (27%) of 11 cases had recurrence of HBV infection. Despite the emergence of the mutations, no deaths were due to HBV reactivation or severe cases of hepatitis. In the Cox proportion regression model regarding reactivation hepatitis after transplantation of all enrolled patients, lamivudine therapy was found to be the only favorable factor for the event, with a hazard ratio of 0.122 (95% confidence interval, 0.016-0.908; P = .040). In conclusion, extended lamivudine therapy is safe and effective for the prevention of HBV reactivation in an HSCT setting and significantly decreases reactivation hepatitis after transplantation.
Hsiao
Liang-Tsai
LT
Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Chiou
Tzeon-Jye
TJ
Liu
Jin-Hwang
JH
Chu
Chiau-Jun
CJ
Lin
Yu-Chen
YC
Chao
Ta-Chung
TC
Wang
Wei-Shu
WS
Yen
Chueh-Chuan
CC
Yang
Muh-Hwa
MH
Tzeng
Cheng-Hwai
CH
Chen
Po-Min
PM
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006509:Hepatitis B / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011292:Premedication; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects
D000998:Antiviral Agents; D019259:Lamivudine