A prospective comparative study of prophylactic or therapeutic use of lamivudine for chemotherapy-associated hepatitis B (HBV) reactivation in nowhodgkin's lymphoma (NHL) patients

[[abstract]]Background and Aims: Lamivudine is effective to prevent HBV reactivation for HBV carriers who undergo chemotherapy. However, the best timing of prescribing lamivudine remains unclear. Methods: HBV carriers with newly diagnosed NHL were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment. Group P patients started lamivudine from day 1 of the first course of CHOP chemotherapy until 2 months after completion of chemotherapy. Group T patients received CHOP chemotherapy alone and started lamivudine treat- ment only if serum ALT elevated to greater than 1.5-fold of upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during and within 12 months after chemotherapy. The clinical course of group T patients was compared with that of an identical group of NHL patients who had been prospectively followed-up for the natural course of HBV reactivation (Hepatology 2003; 37: 1320). Results: Baseline characteristics between group P (n=26) and group T (n=25) patients were similar, except that more group T patients had positive HBeAg (2 vs. 8, p = 0.04) and HBVDNA > 1,000,000 copiesimL (3 vs. 9, p=0.05). During chemotherapy, group P patients had fewer HBV reactivation ( I 1.5% vs. 56%, p = 0.001), HBV-related hepati- tis (7.7% vs. 44%, p=0.004), and severe hepatitis (ALT more than 10-fold ULN) (0 vs. 32%, p=0.002). No hepatitis-related death was observed during protocol treatment. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the two groups. However, 3 patients, all in group P, died of HBV reactivation-related hepatitis, 4.8-7.3 months after protocol treatment. Prophylactic lamivudine use and baseline HBVDNA level were independent predictors of HBV reactivation. Therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation, compared with those in the historical group. Conclusion: The duration of lamivudine prophylaxis, which can reduce the incidence and severity of HBV reactivation and hepatitis during chemotherapy, may have to be no less than 8 months after completion of chemotherapy. Therapeutic use of lamivudine, started when ALT ele- vation was noted, does not appear to change the natural course of HBV reactivation