Chi Heng, Hansen Bettina E, Guo Simin, Zhang Ning Ping, Qi Xun, Chen Liang, Guo Qing, Arends Pauline, Wang Ji-Yao, Verhey Elke, de Knegt Robert J, Xie Qing, Janssen Harry L A
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
J Infect Dis. 2017 Apr 1;215(7):1085-1093. doi: 10.1093/infdis/jix024.
We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t)ide analogue (NA) therapy, compared with continued NA monotherapy.
This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for >12 months and had an HBV DNA load of <2000 IU/mL. Patients were randomly assigned in a 1:1 ratio to 48 weeks of peginterferon add-on therapy (n = 39) or continued NA monotherapy (n = 38). Response (defined as HBeAg seroconversion with an HBV DNA load of <200 IU/mL) was assessed at week 48, with responders discontinuing NA therapy at week 72.
The primary end point (response at week 96) was achieved in 18% of patients who were assigned peginterferon add-on therapy versus 8% of patients assigned NA monotherapy (P = .31). Among 58 interferon-naive patients, add-on therapy led to a greater frequency of HBeAg seroconversion (30% vs 7%; P = .034) and response (26% vs 7%; P = .068) at week 96, compared with monotherapy. Among 8 responders at week 48 who discontinued NA therapy at week 72, 6 patients (75%) maintained a response until week 96 (4 of 6 [67%] in the add-on therapy group vs 2 of 2 [100%] in the monotherapy group; P = 1.00). Adverse events were mainly related to peginterferon.
The primary end point was negative, but peginterferon add-on therapy appeared to result in a greater frequency of HBeAg seroconversion, compared with NA monotherapy, in interferon-naive patients receiving NA therapy.
NCT01532843.
我们研究了与继续接受核苷（酸）类似物（NA）单药治疗相比，聚乙二醇化干扰素α-2b（聚乙二醇干扰素）联合治疗48周是否能提高接受NA治疗的乙肝病毒（HBV）e抗原（HBeAg）阳性患者的血清学应答。
这项随机试验纳入了代偿性肝病的HBeAg阳性患者，这些患者接受恩替卡韦/替诺福韦治疗超过12个月且HBV DNA载量<2000 IU/mL。患者按1:1比例随机分配至聚乙二醇干扰素联合治疗48周组（n = 39）或继续NA单药治疗组（n = 38）。在第48周评估应答情况（定义为HBeAg血清学转换且HBV DNA载量<200 IU/mL），应答者在第72周停用NA治疗。
接受聚乙二醇干扰素联合治疗的患者中18%达到主要终点（第96周的应答），而接受NA单药治疗的患者为8%（P = 0.31）。在58例既往未接受过干扰素治疗的患者中，与单药治疗相比，联合治疗在第96周导致更高频率的HBeAg血清学转换（30%对7%；P = 0.034）和应答（26%对7%；P = 0.068）。在第48周应答且在第72周停用NA治疗的8例患者中，6例患者（75%）维持应答至第96周（联合治疗组6例中的4例[67%]对单药治疗组2例中的2例[100%]；P = 1.00）。不良事件主要与聚乙二醇干扰素有关。
主要终点为阴性，但在接受NA治疗的既往未接受过干扰素治疗的患者中，与NA单药治疗相比，聚乙二醇干扰素联合治疗似乎导致更高频率的HBeAg血清学转换。
NCT01532843。
