Stelma F, van der Ree M H, Jansen L, Peters M W, Janssen H L A, Zaaijer H L, Takkenberg R Bart, Reesink H W
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
J Viral Hepat. 2017 Dec;24(12):1107-1113. doi: 10.1111/jvh.12738. Epub 2017 Jul 29.
Combining peginterferon-alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 μg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti-HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti-HBs antibodies.
聚乙二醇干扰素α-2a（pegIFN）与核苷类似物联合使用比单独使用任何一种疗法都能导致更高的HBsAg消失率。在此，我们对慢性乙型肝炎（CHB）患者联合治疗5年随访后的反应持久性进行了研究。在初始研究中，92例HBV DNA>100 000 c/mL（约20 000 IU/mL）且患有活动性肝炎的CHB患者（44例HBeAg阳性，48例HBeAg阴性）接受了为期48周的治疗，每周使用180 μg pegIFN和每日10 mg阿德福韦酯。对于长期随访（LTFU）研究，患者在治疗结束后进行了5年的随访。在第5年，70例（32例HBeAg阳性，38例HBeAg阴性）患者仍在研究中。在第5年，19%（6/32）的HBeAg阳性患者和16%（6/38）的HBeAg阴性患者HBsAg消失，未观察到HBsAg血清学逆转。HBeAg阳性患者5年累积Kaplan-Meier估计的HBsAg消失率为17.2%，HBeAg阴性患者为19.3%。在随访期间任何时间点HBsAg消失的16例患者中有14例产生了抗-HBs抗体（>10 IU/L）。在第5年，总计63%（20/32）的HBeAg阳性患者和71%（27/38）的HBeAg阴性患者在随访期间再次接受了核苷（酸）类似物治疗。5年累积Kaplan-Meier估计的再次治疗率在第5年为60%的患者。在随访第5年时，接受pegIFN/核苷类似物联合治疗的CHB患者中有18%出现了持久的HBsAg消失，其中88%产生了抗-HBs抗体。
