Chiu Shao-Ming, Kuo Yuan-Hung, Wang Jing-Houng, Hung Chao-Hung, Hu Tsung-Hui, Lu Sheng-Nan, Chen Chien-Hung
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chiyai Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Clin Gastroenterol Hepatol. 2020 Dec;18(13):2989-2997.e3. doi: 10.1016/j.cgh.2020.04.048. Epub 2020 Apr 27.
BACKGROUND & AIMS: We compared rates of relapse of hepatitis B virus (HBV) infection between patients with HBV genotype B vs genotype C infection after cessation of entecavir or tenofovir disoproxil fumarate (TDF) therapy. All patients included in the study were HB e antigen (HBeAg)-negative.
We performed a retrospective study of 460 HBeAg-negative patients without cirrhosis in Taiwan who had stopped entecavir or TDF treatment for at least 12 months; data were collected from 2007 through 2016. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. Patients were evaluated every 1-3 months during the first 6 months after stopping therapy and then every 3 months until their last hospital visit; HB surface antigen (HBsAg) was measured in serum samples collected before treatment, after 12 months of treatment, and at the end of treatment. Virologic relapse was defined as a serum level of HBV DNA >2000 IU/mL after the cessation of treatment; clinical relapse was defined as increase in alanine aminotransferase more than 2-fold the upper limit of normal (40 U/L) and level of HBV DNA >2000 IU/mL after stopping treatment.
Significantly higher proportions of patients with HBV genotype B infection had virologic and clinical relapse and retreatment than patients with HBV genotype C infection, among all patients and among patients matched by propensity sore. Patients who discontinued TDF therapy had significantly higher rates and earlier times of virologic and clinical relapse than patients who discontinued entecavir therapy, among all patients and propensity score-matched patients. Multivariate analysis showed that TDF therapy, old age, HBV genotype B, and higher end of treatment HBsAg level were independently associated with virologic and clinical relapse. Five-year rates of virologic and clinical relapse were low (19.2% and 15.4%, respectively) in patients with a combination of end of treatment level of HBsAg of 100 IU/mL or less and HBV genotype C infection. Rates of off-therapy HBsAg loss, development of hepatocellular carcinoma, and hepatic decompensation did not differ significantly between patients with HBV genotypes B vs C infection or between the entecavir vs TDF groups.
Higher proportions of HBeAg-negative patients with HBV genotype B infection have virologic and clinical relapse and retreatment than patients with HBV genotype C infection, after cessation of entecavir or TDF therapy.
我们比较了乙型肝炎病毒（HBV）基因B型感染患者与基因C型感染患者在恩替卡韦或替诺福韦酯（TDF）治疗停药后HBV感染的复发率。纳入研究的所有患者均为乙肝e抗原（HBeAg）阴性。
我们对台湾460例无肝硬化的HBeAg阴性患者进行了一项回顾性研究，这些患者已停用恩替卡韦或TDF治疗至少12个月；数据收集时间为2007年至2016年。所有患者均符合亚太肝脏研究学会（APASL）2012年指南提出的停药标准。在停药后的前6个月，每1 - 3个月对患者进行评估，之后每3个月评估一次，直至其最后一次就诊；在治疗前、治疗12个月后及治疗结束时采集血清样本检测乙肝表面抗原（HBsAg）。病毒学复发定义为治疗停止后血清HBV DNA水平>2000 IU/mL；临床复发定义为停药后谷丙转氨酶升高超过正常上限（40 U/L）的2倍且HBV DNA水平>2000 IU/mL。
在所有患者以及倾向评分匹配的患者中，HBV基因B型感染患者出现病毒学和临床复发及再次治疗的比例显著高于HBV基因C型感染患者。在所有患者以及倾向评分匹配的患者中，停用TDF治疗的患者病毒学和临床复发的发生率及时间显著早于停用恩替卡韦治疗的患者。多因素分析显示，TDF治疗、老年、HBV基因B型以及治疗结束时较高的HBsAg水平与病毒学和临床复发独立相关。治疗结束时HBsAg水平≤100 IU/mL且为HBV基因C型感染的患者，其5年病毒学和临床复发率较低（分别为19.2%和15.4%）。HBV基因B型与C型感染患者之间或恩替卡韦与TDF组之间，停药后HBsAg消失率、肝细胞癌发生率及肝失代偿发生率无显著差异。
在停用恩替卡韦或TDF治疗后，HBeAg阴性的HBV基因B型感染患者出现病毒学和临床复发及再次治疗的比例高于HBV基因C型感染患者。
