Abstract:

Objective　To analyze the safety of Polyethylene glycol interferon α-2b (PEG-IFNα-2b) in the treatment of chronic hepatitis B (CHB) with low hepatitis B e antigen (HBeAg) level, and to explore the related factors to predict the efficacy. Methods　The clinical data of 188 CHB patients with HBeAg positive and quantitative < 50 S/CO who received PEG-IFNα-2b treatment for the first time in Yantai Qishan Hospital from June 2020 to June 2023 were retrospectively analyzed. Among them, there were 137 males and 51 females, aged (35.04±7.13) years, and the weekly dose of PEG-IFNα-2b was (122.45±27.59) µg. The patients receiving nucleoside (acid) analogues (NAs) were given PEG-IFNα-2b once a week in addition to the original treatment; the patients receiving antiviral therapy for the first time were injected with PEG-IFNα-2b only once a week. If HBeAg turned negative before 48 weeks of treatment, the treatment was consolidated for 12 weeks, otherwise, the treatment was extended to 72 to 96 weeks. According to the efficacy of interferon, they were divided into a HBeAg negative group and a HBeAg non-negative group. The incidence of adverse reactions during the treatment was counted, and the baseline characteristics, biochemical indicators, and virological markers were analyzed. t test, χ² test, and rank sum test were used. Multivariate logistic regression analysis was used to analyze the early factors affecting the efficacy of PEG-IFNα-2b, and the receiver operating characteristic curve (ROC) was used to evaluate the predictive efficacy of related influencing factors on the efficacy. Results　Among the 188 patients, 41 cases (21.81%), 58 cases (30.85%), 74 cases (39.36%), and 89 cases (47.34%) achieved HBeAg negative conversion after 12, 24, 48, and 96 weeks of treatment. During the treatment, 151 patients (80.32%) had adverse reactions. After intervention, 119 cases (78.81%) were improved. There were statistically significant differences in administration regimen, hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B virus deoxyribonucleic acid (HBV DNA), HBV pregenomic RNA (pgRNA), hepatitis B core-related antigen (HBcrAg), treatment time, and treatment compliance between the two groups (all P<0.05). Multivariate logistic regression analysis showed that administration regimen (OR=0.536, 95%CI=0.348-0.826), treatment compliance (OR=0.461, 95%CI=0.256-0.831), treatment time (OR=0.546, 95%CI=0.315-0.948), HBeAg (OR=1.876, 95%CI=1.537-2.289), pgRNA (OR=2.070, 95%CI=1.256-3.412), and HBcrAg (OR=1.602, 95%CI=1.134-2.263) were all early influencing factors for the efficacy of PEG-IFN in the treatment of CHB with low HBeAg level (all P<0.05). ROC analysis showed that the above related factors had certain predictive value for the efficacy of PEG-IFNα-2b in the treatment of CHB with low HBeAg level. Conclusion　Administration regimen, treatment compliance, treatment time, HBeAg, pgRNA, and HBcrAg are all early associated factors for the efficacy of PEG-IFNα-2b in the treatment of CHB with low HBeAg level, and have certain value in predicting the efficacy.

Key words:

Hepatitis B, Polyethylene glycol interferon α-2b, Safety, Curative effect, Predictive factors

摘要：

目的　分析聚乙二醇干扰素α-2b（PEG-IFNα-2b） 治疗低乙型肝炎e抗原（HBeAg）水平慢性乙型肝炎的安全性，并探讨预测疗效的相关因素。方法　回顾性分析2020年6月至2023年6月于烟台市奇山医院首次接受PEG-IFNα-2b治疗的188例HBeAg阳性且定量<50 S/CO的慢性乙型肝炎患者临床资料，其中男137例，女51例，年龄（35.04±7.13）岁，PEG-IFNα-2b每周给药剂量（122.45±27.59）µg。正在接受核苷（酸）类似物（NAs）治疗的患者在原治疗基础上加用PEG-IFNα-2b，每周注射1次；首次接受抗病毒治疗的患者仅注射PEG-IFNα-2b，每周1次。若治疗48周前HBeAg转阴则巩固治疗12周，否则延长治疗至72～96周。根据疗效将患者分为HBeAg转阴组和HBeAg未转阴组。统计治疗过程中患者不良反应发生情况，分析其基线特征、生化指标及病毒学标志物。采用t检验、χ²检验、秩和检验，应用多因素logistic回归分析影响PEG-IFNα-2b疗效的早期因素，并以受试者操作特征曲线（ROC）评估相关影响因素对疗效的预测效能。结果　188例患者中，治疗12周、24周、48周、96周时分别有41例（21.81%）、58例（30.85%）、74例（39.36%）、89例（47.34%）患者实现HBeAg转阴；治疗过程中，有151例（80.32%）患者出现不良反应，经干预后119例（78.81%）患者得到好转。HbeAg转阴组和未转阴组的给药方案、入院时的乙型肝炎表面抗原（HBsAg）、HBeAg、乙型肝炎病毒脱氧核糖核酸（HBV DNA）、HBV前基因组RNA（pgRNA）、乙型肝炎核心相关抗原（HBcrAg）水平及治疗时间、治疗依从性比较，差异均有统计学意义（均P<0.05）；多因素logistic回归分析显示，给药方案（OR=0.536，95%CI=0.348～0.826）、治疗依从性（OR=0.461，95%CI=0.256～0.831）、治疗时间（OR=0.546，95%CI=0.315～0.948）、HBeAg（OR=1.876，95%CI=1.537～2.289）、pgRNA（OR=2.070，95%CI=1.256～3.412）、HBcrAg（OR=1.602，95%CI=1.134～2.263）均是PEG-IFNα-2b治疗低HBeAg水平慢性乙型肝炎疗效的早期影响因素（均P<0.05）；ROC分析显示，上述相关因素均对PEG-IFNα-2b治疗低HBeAg水平慢性乙型肝炎疗效具有一定预测价值。结论　给药方案、治疗依从性、治疗时间、HBeAg、pgRNA、HBcrAg均是PEG-IFNα-2b治疗低HBeAg水平慢性乙型肝炎疗效的早期关联因素，且对疗效预测具有一定价值。

关键词:

慢性乙型肝炎, 聚乙二醇干扰素α-2b, 安全性, 疗效, 预测因素