Peg-IFN治疗NAs经治HBeAg阴性CHB患者的疗效分析及预测  

Clinical efficacy and prediction of pegylated interferon treatment on HBeAg-negative chronic hepatitis B patients who had received nucleoside analogues treatment

作　　者：高明健 胡琴 郭皓宇 李倩 侯周华[1,5] GAO Ming-jian;HU Qin;GUO Hao-yu;LI Qian;HOU Zhou-hua(Department of Infectious Diseases,Xiangya Hospital,Central South University,Changsha 410008,China;Department of Pharmacy,Xiangya Hospital,Central South University,Changsha 410008,China;Department of Infectious Diseases,Changsha Central Hospital Affiliated to University of South China,Changsha 410004,China;Department of Tuberculosis,Hunan Chest Hospital,Changsha 410013,China;National Clinical Medical Research Center for Geriatric Disorders,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院感染病科,湖南长沙410008 [2]中南大学湘雅医院药学部,湖南长沙410008 [3]南华大学附属长沙市中心医院感染性疾病科,湖南长沙410004 [4]湖南省胸科医院结核病科,湖南长沙410013 [5]国家老年疾病临床医学研究中心(湘雅),湖南长沙410008

出　　处：《中国感染控制杂志》2024年第6期665-673,共9页Chinese Journal of Infection Control

基　　金：国家自然科学基金面上项目(82270657);长沙市自然科学基金项目(kq2202368)。

摘　　要：目的探讨聚乙二醇干扰素α-2b(Peg-IFNα-2b)联合核苷(酸)类似物(NAs)治疗NAs经治的乙型肝炎病毒e抗原(HBeAg)阴性慢性乙型病毒性肝炎(CHB)患者的疗效及其影响因素,以及白细胞介素(IL)-28B和程序性死亡受体-1(PD-1)的单核苷酸多态性与干扰素治疗应答的相关性。方法回顾性收集2020年1月—2022年12月就诊于中南大学湘雅医院HBeAg阴性的CHB患者,以Peg-IFNα-2b联合NAs治疗为研究组,NAs单药继续治疗为对照组,分析两组患者在治疗的第12、24、48周的临床疗效,以及第72周患者持续应答及复发情况,并采用PD-1及IL-28B单核苷酸多态性评估HBeAg阴性CHB患者对干扰素治疗应答的价值。结果在治疗的第48周,研究组HBeAg阴性CHB患者应答率[52.05%(38/73)]高于对照组[1.64%(1/61),P<0.05];研究组HBeAg阴性CHB患者中基线HBsAg<100 IU/mL相较于HBsAg≥1000 IU/mL、HBsAg<1000 IU/mL相较于HBsAg≥1000 IU/mL的患者治疗第48周应答率均更高(均P<0.05);单因素和多因素分析显示,研究组HBeAg阴性CHB患者中HBsAg基线水平(OR=1.004,95%CI:1.001~1.006)和治疗第24周HBsAg下降幅度(OR=0.111,95%CI:0.034~0.362)是干扰素联合NAs治疗应答的影响因素(均P<0.05);单核苷酸多态性分析结果显示,研究组HBeAg阴性CHB患者中PD-1 rs10204525 C/T杂合突变型在应答人群占比更高(66.67%VS 16.67%,P<0.05),而IL-28B无明显差异(P>0.05)。结论NAs经治的HBeAg阴性CHB患者联合Peg-IFNa-2b治疗可达到更高的HBsAg清除率和血清学转换率,治疗第24周HBsAg下降幅度可较好地预测治疗第48周的应答。低HBsAg基线水平患者及携带PD-1 rs10204525C/T杂合突变基因的患者接受Peg-IFNa-2b的疗效更佳。Objective To explore the efficacy and influencing factors of polyethylene glycol interferonα-2b(Peg-IFNα-2b)combined nucleoside analogues(NAs)in the treatment of hepatitis B virus e-antigen(HBeAg)-negative chronic hepatitis B(CHB)patients who had received NAs treatment,and evaluate the correlation of mononucleotide polymorphisms of interleukin-28B and programmed death receptor-1(PD-1)with interferon treatment response.Methods HBeAg-negative CHB patients who visited Xiangya Hospital of Central South University from January 2020 to December 2022 were analyzed retrospectively.Patients with Peg-IFNα-2b and NAs treatment were as the study group,while those with NAs therapy alone as the control group.Clinical efficacy of two groups of patients at the 12nd,24th,and 48th weeks of treatment,as well as the persistent response and recurrence at the 72nd week were analyzed.PD-1 and IL-28B single nucleotide polymorphisms were adopted to evaluate the value of HBeAg-negative CHB patients in response to interferon treatment.Results At the 48th week of treatment,the response rate of HBeAg-negative CHB patients in the study group was higher than that in the control group(52.05%[38/73]vs 1.64%[1/61],P<0.05).Among HBeAg-negative CHB patients in the study group,response rates at 48th week of treatment in patients with baseline HBsAg<100 IU/mL and HBsAg<1000 IU/mL were higher than those with HBsAg≥1000 IU/mL,respectively(both P<0.05).Univariate and multivariate analyses showed that in HBeAg-negative CHB patients in the study group,the baseline HBsAg levels(OR=1.004,95%CI:1.001-1.006)and HBsAg decline magnitude at the 24th week of treatment(OR=0.111,95%CI:0.034-0.362)were influencing factors for the response of interferon treatment combined with NAs(both P<0.05).The results of single nucleotide polymorphism analysis showed that in HBeAg-negative CHB patients in the study group,the proportion of PD-1 rs10204525 C/T heterozygous mutation in the response population was higher(66.67%vs 16.67%,P<0.05),while that of IL-28B mutation was

关 键 词：慢性乙型病毒性肝炎 聚乙二醇干扰素Α-2B 单核苷酸多态性 白细胞介素-28B 程序性死亡受体-1 PD-1 

分 类 号：R512.62[医药卫生—内科学]