Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4-to 8-week intervals for the first year and then 4-to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P < .008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P ؍ .002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P ؍ .021). I n an endemic area for chronic hepatitis B infection, exacerbation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. 1,2 Careful prospective serologic testing has shown that liver damage due to exacerbation of hepatitis B virus (HBV) is a 2-stage process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterized by enhanced viral replication, as reflected by increases in serum levels of HBV DNA, hepatitis B e antigen, and HBV DNA polymerase, which presumably results in widespread infection of hepatocytes. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this may lead to hepatitis, hepatic failure, and even death. [3][4][5] In keeping with these observations, our recent data suggest that a high pretreatment level of serum HBV DNA is the single most important factor for exacerbation of HBV after intense immunosuppression. 6 In the past few decades, hematopoietic cell transplantation has been established as the standard treatment of various hematologic and oncologic problems. 7 In areas such as Southeast Asia, where HBV infection is prevalent, hematopoietic cell transplantation might be complicated by HBV-related morbidity and mortality. 8 The pre-heAbbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBV, antibody to hepatitis B virus; PCR, polymerase chain ...