Durability of antiviral response in lamivuidne treated HBeAg positive chronic hepatitis B patients who did not relapse within a year of post treatment

초록

Introduction: On the contrary to Western reports, relapse rate after lamivudine (LMV) discontinuation in HBeAg positive chronic hepatitis B (CHB) patients is higher in Asian patients and most reported relapses occur within 1 year after LMV discontinuation. The aim of this study was to investigate the long-term relapse rate and associated risk factors in HBeAg positive CHB patients who had kept a sustained virologic response (VR) for 1 year after LMV discontinuation. Methods: 376 treatment naïve HBeAg positive CHB patients who took LMV were enrolled. Among them, 113 patients were achieved VR and then discontinued LMV. During the post treatment follow up, 58 of 113 patients (51.3%) showed relapse within 1 year. For the remaining 55 patients who maintained the VR within a year of treatment discontinuation, cumulative rate and risk factor for long-term post treatment relapse were analyzed. VR was defined as loss of HBeAg and undetectable serum DNA in hybridization assay or serum HBV DNA level less than 105 copies/mL. Relapse was defined as reappearance of HBV DNA or increase of HBV DNA more than 105 copies/mL. Delayed relapse was defined as relapse that occurred after sustained VR for 1 year after LMV discontinuation. Results: The baseline characteristics of 55 patients were follows as: Mean age, serum ALT, HBV DNA, duration of LMV treatment, duration of LMV consolidation, and follow up duration after LMV discontinuation was 39.2 years, 374.5 IU/L, 7.5 log10 copies/mL, 22.5 months,10.5 months (range, 0-28), and 38.8 months (range, 14-95), respectively. During follow up period (mean 26.7 months; range, 2-83), 16 of 55 patients (29%) showed delayed relapse. Cumulative rate of delayed relapse from 1 year after LMV discontinuation was 16%, 29%, 39%, 44% at 1, 2, 3, 4 years, respectively. At relapse, 2 patients showed decompensation and three patients showed flare of hepatitis. In univariate analysis, age, pretreatment albumin, serum HBV DNA > 2000 copies/ml at 3 months after LMV discontinuation predicted the delayed relapse significantly. In multivariate analysis, age(P=0.029) and serum HBV DNA > 2000 copies/mL after 3 months of LMV discontinuation (P=0.047) were significant predictors of delayed relapse. Conclusion: Even in patients who had kept sustained VR for 1 year after LMV discontinuation, delayed relapse are not infrequent. Therefore, a LMV maintenance therapy might be considered in HBeAg positive CHB patients who achieved VR weighing the risk and benefit.