BACKGROUND Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. AIMS To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. METHODS Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN. RESULTS Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). CONCLUSIONS PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).

中文翻译：

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低乙肝表面抗原和HBV DNA水平可预测乙肝e抗原阳性慢性乙肝患者对恩替卡韦添加聚乙二醇化干扰素的反应。

背景技术已经评估了聚乙二醇干扰素（PEG-IFN）和核苷酸（t）类似物的各种治疗组合对慢性乙型肝炎（CHB）的疗效，但最佳治疗方案仍不清楚。目的研究与恩替卡韦（ETV）单药治疗相比，PEG-IFN附加药物是否能增加反应，以及ETV预处理的持续时间是否会影响反应。方法对先前在两项随机对照试验中治疗过的HBeAg阳性患者进行评估。患者接受ETV预处理至少24周，然后被分配24-48周的ETV + PEG-IFN附加治疗，或继续进行ETV单药治疗。响应定义为停药PEG-IFN后48周HBeAg丢失并结合HBV DNA <200 IU / mL。结果在234例患者中，有118例接受了PEG-IFN附加治疗，有116例继续进行了ETV单药治疗。在接受附加疗法治疗的患者中有38/118（33％）的患者和接受单一疗法的患者中有23/116（20％）的患者观察到了反应（P = 0.03）。在随机分组的HBsAg水平低于4000 IU / mL且HBV DNA水平低于50 IU / mL的PEG-IFN初治患者中，观察到对单药治疗的最高反应（70％vs 34％； P = 0.01）。高于临界水平，治疗组之间的反应很低且无明显差异。ETV预处理的持续时间与HBsAg和HBV DNA水平相关（均P <0.005），但与反应无关（P = 0.82）。结论与ETV单药治疗相比，HBeAg阳性CHB患者与ETV治疗相比，PEG-IFN联合治疗具有更高的应答率。在HBsAg低于4000 IU / mL而HBV DNA低于50 IU / mL的PEG-IFN初治患者中，应答增加了一倍，