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Clin Gastroenterol Hepatol. 2020 Apr 27. pii: S1542-3565(20)30593-0. doi: 10.1016/j.cgh.2020.04.048. [Epub ahead of print]
Associations of HBV Genotype B vs C Infection With Relapse After Cessation of Entecavir or Tenofovir therapy.
Chiu SM1, Kuo YH1, Wang JH1, Hung CH2, Hu TH1, Lu SN2, Chen CH3.
Author information
1
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung.
2
Chiyai Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
3
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung. Electronic address: [email protected].
Abstract
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.
METHODS:
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 2015. 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.
RESULTS:
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.
CONCLUSIONS:
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.
我们对台湾停止使用恩替卡韦或TDF治疗至少12个月的460例无肝硬化的HBeAg阴性患者进行了回顾性研究。数据收集自2007年至2015年。所有患者均符合APASL 2012指南提出的停止标准。在停止治疗后的最初6个月中，每1-3个月对患者进行一次评估，然后每3个月评估一次，直到他们最后一次就诊为止。在治疗前，治疗12个月后和治疗结束时采集的血清样本中测量HB表面抗原（HBsAg）。病毒学复发的定义是停止治疗后，血清HBV DNA水平> 2000 IU / mL。临床复发定义为停止治疗后丙氨酸转氨酶的增加超过正常上限（40 U / L）的2倍以上，并且HBV DNA的水平> 2000 IU / mL。
结果：
在所有患者中和倾向疮相匹配的患者中，与HBV基因型C感染的患者相比，具有HBV基因型B感染的患者进行病毒学和临床复发及再治疗的比例要高得多。在所有患者和倾向评分匹配的患者中，中止TDF治疗的患者比中止恩替卡韦治疗的患者具有更高的病毒学和临床复发率，并且复发时间更早。多因素分析表明，TDF治疗，老年，HBV基因型B和治疗结束时HBsAg水平与病毒学和临床复发均独立相关。 HBsAg治疗结束水平为100 IU / mL或以下且HBV基因型为C感染的患者，其五年病毒学和临床复发率较低（分别为19.2％和15.4％）。 HBV基因型B vs C感染的患者或恩替卡韦与TDF组之间的非治疗性HBsAg丢失率，肝细胞癌的发生率和肝失代偿率无显着差异。
结论：