Papatheodoridis George V, Rigopoulou Eirini I, Papatheodoridi Margarita, Zachou Kalliopi, Xourafas Vassilios, Gatselis Nikolaos, Hadziyannis Emilia, Vlachogiannakos John, Manolakopoulos Spilios, Dalekos George N
Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece.
Antivir Ther. 2018;23(8):677-685. doi: 10.3851/IMP3256.
The remission rates after stopping antivirals in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) vary among studies, while reliable predictors of relapse have not been identified. This prospective study assessed rates and predictors of relapse and retreatment in 57 non-cirrhotic hepatitis B surface antigen (HBsAg)-positive patients with HBeAg-negative CHB who discontinued effective ≥4-year entecavir or tenofovir disoproxil fumarate (TDF) therapy.
A total of 57 patients discontinued therapy after median virological remission of 5.3 years and remained under close follow-up. They were retreated with entecavir/TDF if they fulfilled predetermined criteria.
During median follow-up of 18 months, no patient died, developed jaundice or liver decompensation. The cumulative relapse rates varied according to HBV DNA and alanine aminotransferase cutoffs; for HBV DNA >2,000 IU/ml, they were 56%, 70% and 72% at 3, 12 and 18 months after stopping entecavir/TDF. The cumulative probability of retreatment was 18% and 26% at 3 and 12 months being significantly affected only by pretreatment fibrosis severity (adjusted relative hazard: 3.43; P=0.015). Cumulative rates of HBsAg loss were 5%, 16% and 25% at 6, 12 and 18 months being higher in patients with lower HBsAg levels at treatment discontinuation.
Our prospective study shows that effective ≥4-year entecavir/TDF therapy can be safely discontinued in non-cirrhotic HBeAg-negative CHB patients. The probability of relapse decreased after month 6. Despite common virological relapses, most patients, particularly those with mild-moderate pretreatment fibrosis, remain without retreatment, at least in the first 18 months, as a substantial proportion of them clear HBsAg and the majority eventually enters into an inactive carrier state.
在乙型肝炎e抗原（HBeAg）阴性慢性乙型肝炎（CHB）患者中，停用抗病毒药物后的缓解率在不同研究中有所差异，且尚未确定复发的可靠预测因素。本前瞻性研究评估了57例非肝硬化、乙型肝炎表面抗原（HBsAg）阳性、HBeAg阴性CHB患者在停用恩替卡韦或替诺福韦酯（TDF）进行≥4年有效治疗后的复发率、再治疗率及预测因素。
共57例患者在病毒学缓解中位数达5.3年后停药，并接受密切随访。若符合预定标准，则用恩替卡韦/TDF进行再治疗。
在中位随访18个月期间，无患者死亡、出现黄疸或肝失代偿。累积复发率根据乙肝病毒（HBV）DNA和丙氨酸氨基转移酶临界值而异；对于HBV DNA>2000 IU/ml，在停用恩替卡韦/TDF后3、12和18个月时，累积复发率分别为56%、70%和72%。再治疗的累积概率在3个月和12个月时分别为18%和26%，仅受治疗前纤维化严重程度的显著影响（校正相对风险：3.43；P = 0.015）。在停药时HBsAg水平较低的患者中，6、12和18个月时HBsAg消失的累积率分别为5%、16%和25%。
我们的前瞻性研究表明，在非肝硬化HBeAg阴性CHB患者中，可以安全地停用≥4年的恩替卡韦/TDF有效治疗。6个月后复发概率降低。尽管常见病毒学复发，但大多数患者，尤其是那些治疗前纤维化程度为轻至中度的患者，至少在最初18个月内无需再治疗，因为其中很大一部分患者清除了HBsAg，且大多数最终进入非活动携带者状态。
