Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.
BACKGROUND & AIMS: Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a.
Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485).
200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated.
For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success.
在接受核苷（酸）类似物治疗的慢性乙型肝炎（CHB）患者中，治疗后持久应答并不常见。本研究评估了接受长期恩替卡韦（ETV）治疗的患者转换为聚乙二醇干扰素 alfa-2a 后的应答、应答预测因子和安全性。
接受 ETV 治疗 9-36 个月、HBeAg <100 PEIU/ml 且 HBV DNA <1000 拷贝/ml 的 HBeAg 阳性 CHB 患者，按 1:1 随机分为接受聚乙二醇干扰素 alfa-2a 180 μg/周或 ETV 0.5mg/天治疗 48 周。主要终点为第 48 周时 HBeAg 血清学转换（ClinicalTrials.gov：NCT00940485）。
200 例患者随机分组，197 例患者接受了至少 1 个研究药物剂量。5 例基线时抗-HBe 阳性的患者被排除在改良意向治疗人群之外（聚乙二醇干扰素 alfa-2a 组，n=94；ETV 组，n=98）。转换为聚乙二醇干扰素 alfa-2a 的患者在第 48 周时的 HBeAg 血清学转换率高于继续接受 ETV 治疗的患者（14.9% vs. 6.1%；p=0.0467）。只有接受聚乙二醇干扰素 alfa-2a 治疗的患者实现了 HBsAg 丢失（8.5%）。在随机分组时 HBeAg 丢失且 HBsAg <1500 IU/ml 的聚乙二醇干扰素 alfa-2a 治疗患者中，分别有 33.3%和 22.2%的患者实现了 HBeAg 血清学转换和 HBsAg 丢失。治疗早期 HBsAg 下降可预测第 48 周时的应答；在第 12 周时 HBsAg <200 IU/ml 的患者中观察到最高的应答率（HBeAg 血清学转换，66.7%；HBsAg 丢失，77.8%）。丙氨酸氨基转移酶升高与病毒反弹无关（n=38）。聚乙二醇干扰素 alfa-2a 耐受性良好。
对于 ETV 治疗实现病毒学抑制的患者，转换为有限疗程的聚乙二醇干扰素 alfa-2a 可显著提高 HBeAg 血清学转换和 HBsAg 丢失率。应答指导方法可能有助于识别最有可能成功的患者。
