慢性乙型肝炎患者停用核苷酸类似物后持续的反应有限：一

StephenW

Hepatology
Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study)

    Kin Seng Liem1,2, Scott Fung1, David K ​​Wong1, Colina Yim1, Seham Noureldin1, Jiayun Chen1, Jordan J Feld1,3, Bettina E Hansen1,4, Harry L A Janssen1

Author affiliations
Abstract

Objective although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, We evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.

Design Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA Therapy.

Results Among 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0–0.4) vs 0.1 (0.0–0.2) log IU/mL in stop vs continued patients). Among patients who stopped, 15/45 (33% Had virological or biochemical relapse and 17/45 (38%) were retreated according to predetermined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment ( Pteen0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.

Conclusion the findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.

Trial registration number NCT01911156.

StephenW

慢性乙型肝炎患者停用核苷酸类似物后持续的反应有限：一项随机对照试验的结果（多伦多停止研究）

Kin Seng Liem1,2，Scott Fung1，David K Wong1，Colina Yim1，Seham Noureldin1，Chenjiayun1，Jordan J Feld1,3，Bettina E Hansen1,4，Harry L A Janssen1

作者单位
抽象

目的尽管大多数慢性乙型肝炎（CHB）患者可以通过长期的核苷酸类似物（NA）治疗获得有效的病毒学抑制，但有些患者可能无需终生治疗。在这项随机，对照，IV期试验中，我们评估了中断长期NA治疗后患者的非治疗结局。

设计接受NA治疗≥1年并在HBeAg阳性患者中达到病毒学抑制（乙型肝炎e抗原（HBeAg）血清转化与HBeAg阳性患者≥12个月或未检测到HBV DNA≥36个月）的患者HBeAg阴性患者）按2：1的比例随机分组，以停止或继续进行NA治疗72周。在停止NA治疗后72周评估持续的疾病缓解（HBeAg阴性，HBV DNA <2000 IU / mL，丙氨酸转氨酶（ALT）正常）。

结果在67名入组患者中，在13/45（29％）停药组中观察到持续疾病缓解，而在18/22（82％）继续患者中观察到。乙肝表面抗原（HBsAg）丢失发生在两名患者中（每组一名）。两组中从随机分组到第72周的中位HBsAg下降相似（停药组与继续组患者的log IU / mL分别为0.2（0.0-0.4）vs 0.1（0.0-0.2）log IU / mL）。在停止治疗的患者中，根据预定标准，接受了15/45（33％的病毒学或生化学复发）和17/45（38％）的患者康复。治疗前HBeAg阳性的总比例为11/18（61％），而6/27（ HBeAg阴性的患者需要再治疗（22％）（Pteen0.01）。ALT超过正常上限（ULN）的10倍以上的患者有14例（31％），ALT超过5倍ULN的患者中有7例（16％）的患者。肝代偿失调或死亡。

结论这项前瞻性研究的结果表明，在慢性乙型肝炎中停止NA治疗的益处有限。

试用注册号NCT01911156。