Lee I-Cheng, Sun Cheuk-Kay, Su Chien-Wei, Wang Yuan-Jen, Chang Hung-Chuen, Huang Hui-Chun, Lee Kuei-Chuan, Huang Yi-Shin, Perng Chin-Lin, Liu Yuh-Hwa, Chua Chian-Sem, Lin Yu-Min, Lin Han-Chieh, Huang Yi-Hsiang
From the Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital (I-CL, C-WS, H-CH, K-CL, Y-SH, C-LP, H-CL, Y-HH); Faculty of Medicine, National Yang-Ming University School of Medicine (I-CL, C-WS, H-CH, K-CL); Division of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital (C-KS, H-CC, Y-HL, C-SC, Y-ML); Health Care Center, Taipei Veterans General Hospital (Y-JW); and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan (I-CL, C-WS, K-CL, Y-HH).
Medicine (Baltimore). 2015 Aug;94(32):e1341. doi: 10.1097/MD.0000000000001341.
Long-term nucleos(t)ide analogues (NUCs) treatment is usually required for patients with chronic hepatitis B (CHB). However, whether discontinuation of NUCs is possible in selected patients remains debated. The aim of this study was to assess the durability of NUCs and predictors of sustained response after cessation of NUCs.Ninety-three CHB patients (29 HBeAg-positive and 64 HBeAg-negative) from 2 medical centers in Taiwan with discontinuation of NUCs after a median of 3 years' treatment were retrospectively reviewed. Fifteen (51.7%) HBeAg-positive and 57 (89.1%) HBeAg-negative patients achieved APASL treatment endpoints. Virological relapse (VR) and clinical relapse (CR) were defined according to APASL guidelines.Achieving APASL endpoint was associated with longer median time to CR in HBeAg-positive patients, but not in HBeAg-negative cases. The cumulative 1-year VR and CR rates were 55.3% and 14.4% in HBeAg-positive patients, and 77.7% and 41.9% in HBeAg-negative patients, respectively. In HBeAg-negative patients, baseline HBV DNA >10 IU/mL was the only predictor of VR (hazard ratio [HR] = 2.277, P = 0.019) and CR (HR = 3.378, P = 0.014). HBsAg >200 IU/mL at the end of treatment (EOT) was associated with CR (HR = 3.573, P = 0.023) in patients developing VR. HBeAg-negative patients with low baseline viral loads and low HBsAg levels at EOT had minimal risk of CR after achieving APASL treatment endpoint (P = 0.016).The VR rate is high, but the risk of CR is low within 1 year with consolidation treatment after HBeAg seroconversion. Longer consolidation treatment to reduce the risk of VR should be considered in HBeAg-positive patients. As high risk of VR and CR, cessation of NUCs therapy could be considered only in selected HBeAg-negative patients.
慢性乙型肝炎(CHB)患者通常需要长期接受核苷(酸)类似物(NUCs)治疗。然而,部分患者是否可以停用NUCs仍存在争议。本研究旨在评估NUCs的治疗持久性以及停用NUCs后持续应答的预测因素。
回顾性分析了来自台湾2个医疗中心的93例CHB患者(29例HBeAg阳性和64例HBeAg阴性),这些患者在接受中位数为3年的治疗后停用了NUCs。15例(51.7%)HBeAg阳性患者和57例(89.1%)HBeAg阴性患者达到了亚太肝脏研究学会(APASL)的治疗终点。病毒学复发(VR)和临床复发(CR)根据APASL指南进行定义。
在HBeAg阳性患者中,达到APASL终点与至CR的中位时间较长相关,但在HBeAg阴性患者中并非如此。HBeAg阳性患者1年累积VR率和CR率分别为55.3%和14.4%,HBeAg阴性患者分别为77.7%和41.9%。在HBeAg阴性患者中,基线HBV DNA>10 IU/mL是VR(风险比[HR] = 2.277,P = 0.019)和CR(HR = 3.378,P = 0.014)的唯一预测因素。在发生VR的患者中,治疗结束时(EOT)HBsAg>200 IU/mL与CR相关(HR =
3.573,P = 0.023)。EOT时基线病毒载量低且HBsAg水平低的HBeAg阴性患者在达到APASL治疗终点后CR风险最小(P = 0.016)。
HBeAg血清学转换后进行巩固治疗,1年内VR率高,但CR风险低。对于HBeAg阳性患者,应考虑延长巩固治疗以降低VR风险。由于VR和CR风险高,仅在部分选择的HBeAg阴性患者中可考虑停用NUCs治疗。