1Center for Database Research, E-Da Hospital, Kaohsiung, Taiwan.
2Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan.
3School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
4Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
5School of Public Health, Fu Jen Catholic University, New Taipei, Taiwan.
6Superintendent Office, Tainan Municipal Hospital, Tainan, Taiwan.
7Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
8Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.
9Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan.
10Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
11National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
12Big Data Research Center, Fu Jen Catholic University, New Taipei, Taiwan.
AbstractBACKGROUND: Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy but the risk of subsequent clinical outcome remains unclear and unpredictable.
AIM: We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy.
METHODS: This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg-negative and viral DNA-undetectable when discontinuing entecavir after at least 3 years on therapy. Following virological relapse (viral DNA >2,000 IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3 months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis.
RESULTS: The cumulative incidence of clinical hepatitis 2 years after virological relapse was 61.0% (95% CI, 49.9-72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9-66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio [HR], 1.31 per log IU/mL; 95% CI, 1.07-1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27-2.10), after adjustment for serum aminotransferase and alfa-fetoprotein levels in the multivariate analysis. Viral DNA >100,000 IU/mL predicted a nearly inevitable occurrence of clinical flare (P < 0.0001).
CONCLUSIONS: A high viral load at the virological relapse predicts subsequent clinical hepatitis in CHB patients who discontinue entecavir. 作者: StephenW 时间: 2017-1-26 16:31
这项多中心队列研究前瞻性地监测了133例CHB患者,HBeAg阴性和病毒DNA在治疗至少3年后停止恩替卡韦时检测不到。在92例患者发生病毒学复发(病毒DNA> 2000 IU / mL)后,确定随后的临床耀斑和持续性(3个月内未出现)或重度肝炎(伴有黄疸或凝血病)的发生率,并探索风险因素。患者在持续性或重度肝炎发生之前没有恢复抗病毒治疗。
结果:
病毒学复发后2年临床肝炎的累积发生率为61.0%(95%CI,49.9-72.3%),持续性或重度肝炎的累积发生率为53.0%(95%CI,40.9-66.2%)。在病毒学复发的血清病毒载量与临床肝炎(校正的风险比[HR],1.31每log IU / mL; 95%CI,1.07-1.60)和持续或重度肝炎(调整的HR,1.63每log IU / mL; 95%CI,1.27-2.10),在多变量分析中调整血清转氨酶和甲胎蛋白水平。病毒DNA> 100,000 IU / mL预测临床发病几乎不可避免的发生(P <0.0001)。
结论: