Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
World J Gastroenterol. 2020 Apr 7;26(13):1525-1539. doi: 10.3748/wjg.v26.i13.1525.
Nucleos(t)ide analog (NA) has shown limited effectiveness against hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) patients.
To evaluate the efficacy and safety of add-on peginterferon α-2a (peg-IFN α-2a) to an ongoing NA regimen in CHB patients.
In this observational study, 195 CHB patients with HBsAg ≤ 1500 IU/mL, hepatitis B e antigen (HBeAg)-negative (including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA) and hepatitis B virus-deoxyribonucleic acid < 1.0 × 10 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December 2018 at the Second Affiliated Hospital of Xi'an Jiaotong University, China. Patients were given the choice between receiving either peg-IFN α-2a add-on therapy to an ongoing NA regimen (add-on group, = 91) or continuous NA monotherapy (monotherapy group, = 104) after being informed of the benefits and risks of the peg-IFN α-2a therapy. Total therapy duration of peg-IFN α-2a was 48 wk. All patients were followed-up to week 72 (24 wk after discontinuation of peg-IFN α-2a). The primary endpoint was the proportion of patients with HBsAg clearance at week 72.
Demographic and baseline characteristics were comparable between the two groups. Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4% (34/91) and 1.9% (2/104) at week 72, respectively. The HBsAg seroconversion rate in the add-on group was 29.7% (27/91) at week 72, and no patient in the monotherapy group achieved HBsAg seroconversion at week 72. The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72 ( < 0.001). Younger patients, lower baseline HBsAg concentration, lower HBsAg concentrations at weeks 12 and 24, greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase ≥ 2 × upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFN α-2a add-on treatment. Regarding the safety of the treatment, 4.4% (4/91) of patients in the add-on group discontinued peg-IFN α-2a due to adverse events. No severe adverse events were noted.
Peg-IFN α-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg ≤ 1500 IU/mL after over 1 year of NA therapy.
核苷（酸）类似物（NA）在慢性乙型肝炎（CHB）患者中对乙型肝炎表面抗原（HBsAg）清除的效果有限。
评估聚乙二醇干扰素 α-2a（peg-IFN α-2a）添加到正在进行的 NA 方案中对 CHB 患者的疗效和安全性。
在这项观察性研究中，2015 年 11 月至 2018 年 12 月，在中国西安交通大学第二附属医院共纳入了 195 例 HBsAg≤1500IU/mL、HBeAg 阴性（包括 HBeAg 阴性患者或 HBeAg 阳性患者，他们在接受 NA 抗病毒治疗后 HBeAg 转阴）和 HBV 脱氧核糖核酸<1.0×10 IU/mL 的 CHB 患者，这些患者在接受 NA 治疗 1 年以上。在告知了 peg-IFN α-2a 治疗的益处和风险后，患者可选择接受 peg-IFN α-2a 添加到正在进行的 NA 方案中（添加组， =91）或继续接受 NA 单药治疗（单药组， =104）。peg-IFN α-2a 的总治疗时间为 48 周。所有患者均随访至 72 周（停止 peg-IFN α-2a 治疗后 24 周）。主要终点是第 72 周时 HBsAg 清除率。
两组的人口统计学和基线特征无差异。意向治疗分析显示，添加组和单药组在第 72 周时 HBsAg 清除率分别为 37.4%（34/91）和 1.9%（2/104）。添加组第 72 周 HBsAg 血清转换率为 29.7%（27/91），而单药组没有患者达到 HBsAg 血清转换。添加组第 72 周 HBsAg 清除率和血清转换率明显高于单药组（<0.001）。年轻患者、较低的基线 HBsAg 浓度、第 12 周和第 24 周较低的 HBsAg 浓度、从基线到第 12 周和第 24 周 HBsAg 更大的下降以及治疗的前 12 周丙氨酸氨基转移酶≥2×正常值上限是 peg-IFN α-2a 添加治疗患者 HBsAg 清除的强预测因素。关于治疗的安全性，添加组有 4.4%（4/91）的患者因不良事件停止了 peg-IFN α-2a 治疗。没有发生严重不良事件。
在接受核苷（酸）类似物治疗 1 年以上的 HBeAg 阴性、HBsAg≤1500IU/mL 的 CHB 患者中，peg-IFN α-2a 作为附加治疗可增强 HBsAg 清除。
