聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎实现临床治愈的预测因素分析

摘要/Abstract

摘要： 目的探究聚乙二醇干扰素α-2b(PEG-IFN α-2b)治疗HBeAg阴性慢性乙型肝炎[HBeAg (-) CHB]患者实现临床治愈的预测因素。方法回顾性研究2016年8月―2020年12月泰州市人民医院收治的PEG-IFN α-2b治疗的HBeAg (-) CHB患者,分为治愈组和未治愈组。单因素分析、logistic多因素分析筛选出临床治愈的预测因素,ROC-AUC评价预测效能。根据ROC-AUC得出的预测因素的截断值分别进行分组,采用Kaplan-Meier生存曲线估算HBsAg累积清除率,Log-rank对数秩检验用于比较组间差异。结果共有116例HBeAg (-) CHB患者入组,随访时间124.93(109.61～140.11)周,临床治愈率为31.03%(36/116)。单因素分析得出有统计学意义的指标:基线HBsAg水平(Z=-6.283,P＜0.001)、基线肝硬化患者的比例(χ²=8.344, P=0.004)、12周和24周HBsAg下降幅度(Z=-3.922、-5.144,P均＜0.001)、疗程中ALT一过性升高的峰值(Z=-6.081,P＜0.001)。多因素分析提示基线HBsAg水平(P=0.001)、治疗24周HBsAg下降幅度(P=0.001)以及疗程中ALT一过性升高的峰值(P=0.019)与临床治愈独立相关。上述三个因素的截断值分别为1.68 lg IU/mL、1.28 lg IU/mL和110.50 U/L,三个因素单独及联合预测临床治愈的AUC分别为0.802、0.855、0.833和0.963。比较基线HBsAg≤1.68 lg IU/mL组和＞1.68 lg IU/mL组、24周HBsAg下降幅度≥1.28 lg IU/mL组和＜1.28 lg IU/mL组、疗程中ALT一过性升高的峰值≥110.50 U/L组和＜110.50 U/L组组间的HBsAg累积清除率,差异均有统计学意义(χ²=30.966、42.925、28.463,P均＜0.001)。结论基线HBsAg水平越低的HBeAg (-) CHB患者,给予PEG-IFNα-2b治疗可获得更高的HBsAg清除率,动态随访中,24周HBsAg下降幅度大、ALT一过性升高峰值大的患者,临床治愈率更高。

关键词: 慢性乙型肝炎, 聚乙二醇干扰素, 临床治愈, 乙型肝炎表面抗原

Abstract: Objective To explore the predictors for functional cure in HBeAg-negative chronic hepatitis B [HBeAg (-)CHB] patients treated with pegylated interferon α-2b (PEG-IFN α-2b). Methods A retrospective study was conducted on HBeAg (-)CHB patients treated with PEG-IFN α-2b from August 2016 to December 2020 in Taizhou People's Hospital, and they were divided into cured group and uncured group. Univariate and logistic multivariate analyses were used to screen out the predictors for the functional cure. ROC-AUC was used to evaluate the predictive efficacy. Patients were grouped according to the cut-off values of predictors derived from ROC-AUC, the accumulated rate of HBsAg seroclearance was estimated by Kaplan-Meier survival curves, and the Log-rank test was used to compare the differences. Results A total of 116 HBeAg (-)CHB patients were included. Median follow-up was 124.93(109.61～140.11)weeks, and the rate of functional cure was 31.03% (36/116). Univariate analysis found that the factors which had statistical differences included the baseline HBsAg level(Z=-6.283, P<0.001), the proportion of cirrhotic patients at baseline(χ²=8.344, P=0.004), HBsAg decline at week 12 and week 24(Z=-3.922 and -5.144 respectively, P<0.001 for all)and the peak value of transient ALT elevation during the treatment (Z=-6.081, P<0.001). Logistic multivariate regression analysis suggested that the baseline HBsAg levels(P=0.001), the magnitude of HBsAg decline at week 24 (P=0.001)and the peak value of transient ALT elevation (P=0.019)were independently associated with functional cure. The cut-off values of the baseline HBsAg, the decline of HBsAg at week 24 and the peak value of transient ALT elevation were 1.68 lg IU/mL, 1.28 lg IU/mL and 110.50 U/L, respectively. The AUCs of the above three factors alone and combined for predicting functional cure were 0.802, 0.855, 0.833 and 0.963, respectively. There were significant differences in the accumulated rate of HBsAg seroclearance between the groups with baseline HBsAg≤1.68 lg IU/mL and ＞1.68 lg IU/mL, the decline of HBsAg≥1.28 lg IU/mL and ＜1.28 lg IU/mL at week 24, the peak value of transient ALT elevation≥110.50 U/L and ＜110.50 U/L during the treatment (χ²=30.966, 42.925,28.463 respectively, P<0.001 for all). Conclusion For HBeAg (-)CHB patients with lower baseline HBsAg levels, the treatment of PEG-IFN α-2b could achieve a higher HBsAg seroclearance rate. Moreover, the functional cure rate could also elevate in patients with a significant HBsAg decline at week 24 and a higher peak value of transient ALT elevation during the treatment.

Key words: Chronic hepatitis B, Pegylated interferon, Functional cure, Hepatitis B surface antigens

顾琳琳, 胡瑞, 窦宇明, 肖丽. 聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎实现临床治愈的预测因素分析[J]. 肝脏, 2023, 28(3): 313-319.

GU Lin-lin, HU Rui, DOU Yu-ming, XIAO Li. Predictors associated with functional cure in HBeAg-negative chronic hepatitis B patients treated with pegylated interferon α-2b[J]. Chinese Hepatolgy, 2023, 28(3): 313-319.

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