核苷（酸）维持治疗转换为 PegIFN alfa-2a 治疗 HBeAg 阳性慢性乙型肝炎患者的效果：一项随机试验。
Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial.
机构信息
Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Department of Internal Medicine, College of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.
出版信息
PLoS One. 2022 Jul 22;17(7):e0270716. doi: 10.1371/journal.pone.0270716. eCollection 2022.
AIMS
Induction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response.
METHODS
Patients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (≤100 IU/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 μg/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy.
RESULTS
We randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all p<0.001). The maximal HBsAg decline in the PegIFN alfa-2a group was at week 36 (0.50±0.88 log10 IU/mL), and this decline was smaller in the NA group (0.08±0.46 log10 IU/mL). The percentage of patients with HBeAg seroconversion at week 48 was also greater in the PegIFN alfa-2a group (15/75 [20.0%] vs. 5/74 [6.8%], p = 0.018). Multivariable analysis indicated the PegIFN alfa-2a group had a greater change in HBeAg seroconversion at week 48 (p = 0.027). Patients had relatively good tolerance to PegIFN alfa-2a therapy.
CONCLUSIONS
CHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy.
TRIAL REGISTRATION
(ClinicalTrials.gov; NCT01769833).
目的
在慢性乙型肝炎（CHB）患者中，即使长期使用核苷（酸）类似物（NA），也难以诱导持久的病毒应答。本研究旨在探讨在长期 NA 治疗后转为聚乙二醇干扰素（PegIFN）alfa-2a 是否能诱导持久的病毒应答。
方法
本研究纳入了接受任何 NA 治疗至少 72 周且 HBV DNA 水平较低（≤100 IU/mL）的 HBeAg 阳性 CHB 患者，按 1:1 比例随机分为 PegIFN alfa-2a（180 μg/周）组或 NA 组，接受 48 周的治疗。主要终点是抗病毒治疗期间乙型肝炎表面抗原（HBsAg）滴度的变化。
结果
本研究共纳入了 149 例 CHB 患者，随机分为两组。与基线相比，两组患者在治疗 12 周时 HBsAg 水平均未降低，但在治疗 24、36 和 48 周时均降低（均 p<0.001）。PegIFN alfa-2a 组 HBsAg 的最大下降幅度出现在治疗 36 周时（0.50±0.88 log10 IU/mL），而 NA 组的下降幅度较小（0.08±0.46 log10 IU/mL）。在治疗 48 周时，PegIFN alfa-2a 组 HBeAg 血清学转换的患者比例也更高（15/75 [20.0%] vs. 5/74 [6.8%]，p = 0.018）。多变量分析表明，PegIFN alfa-2a 组在治疗 48 周时 HBeAg 血清学转换的变化更大（p = 0.027）。患者对 PegIFN alfa-2a 治疗具有较好的耐受性。
结论
与继续接受 NA 治疗的患者相比，转为 PegIFN alfa-2a 治疗 48 周的 CHB 患者的 HBsAg 滴度显著降低，HBeAg 血清学转换率增加。
试验注册
（ClinicalTrials.gov；NCT01769833）。
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