影响聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者疗效的多因素分析

Efficacy of peginterferon alfa-2b treatment and affecting response factors in patients with chronic hepatitis B

目的探讨应用α-干扰素治疗的慢性乙型肝炎(CHB)患者血清干扰素-γ诱导蛋白-10(IP-10)、I型干扰素受体(IFNAR)和辅助性T细胞17(Th-17)水平变化及其对治疗应答的影响。方法2015年6月~2017年12月我科收治的105例CHB患者,采用聚乙二醇化干扰素α-2b治疗48周。采用RT-PCR法检测血清HBVDNA载量,采用双抗体夹心法检测血清干扰素-γ诱导蛋白-10(IP-10),采用RT-PCR法测定外周血单个核细胞α/β干扰素受体(IFNAR-α、IFNAR-β)、辅助性T细胞17(IL-17A)和IL-17F。采用多因素Logistic回归分析影响聚乙二醇化干扰素α-2b治疗CHB患者应答的影响因素。结果在治疗结束时,在105例CHB患者中获得完全应答56例(53.3%),未获得完全应答49例;单因素分析显示获得完全应答与未获得完全应答患者血小板、白蛋白、总胆红素、凝血酶原时间、IFNAR-α和IFNAR-β差异无统计学意义(P>0.05),应答组基线白细胞计数、血清丙氨酸氨基转移酶、HBVDNA、HBsAg、IP-10、IL-17A和、IL-17F水平分别为(5.6±1.7)×10^9/L、(108.6±9.5)U/L、(5.4±0.8)lgcopies/ml、(4.6±0.9)lgIU/ml、(324.5±86.9)pg/ml、(3.2±0.6)平均荧光强度(MFI)、(3.1±0.5)MFI,与未应答组的(6.4±1.9)×10^9/L、(82.5±10.0)U/L、(6.1±0.9)lgcopies/ml、(5.8±1.1)lgIU/ml、(381.4±79.6)pg/ml、(3.8±0.7)MFI、(3.6±0.7)MFI比,差异显著(P<0.05);多因素Logistic回归分析显示,血清HBVDNA、HBsAg、IP-10、IL-17A和IL-17F水平是影响α-干扰素治疗CHB患者应答的因素(P<0.05)。结论除常识性认识到的血清HBVDNA和HBsAg水平外,本研究发现检测血清IP-10和Th-17水平有助于对CHB患者在α-干扰素治疗后应答反应的预测,或许能为临床做出治疗决定有裨益。

Objective To investigate the efficacy of peginterferon alfa-2b treatment and affecting response factors in patients with chronic hepatitis B(CHB).Methods A total of 105 patients with CHB were recruited in our hospital between June 2015 and December 2017,and all patients were treated by peginterferon alfa-2b for 48 weeks.Serum HBV DNA,HBeAg and HBsAg,as well as interferon-γ-induced protein-10(IP-10),interferon-α/βreceptor(IFNAR),and T helper cell 17(Th-17)were detected.Multivariate Logistic regression analysis was applied to demonstrate the prognostic factors of response to peginterferon alfa-2b therapy in patients with CHB.Results At the end of treatment regimen,56 patients(53.3%),while 49 failed to respond to peginterferon alfa-2b therapy;there were no significant differences as respect to blood platelet counts,serum albumin,total bilirubin,prothrombin time,IFNAR-αand IFNAR-βbetween responders and non-responders(P>0.05),while the baseline white blood cell counts,serum alanine aminotransferase,HBV DNA loads,HBsAg,IP-10,IL-17A and IL-17F in the responded group were(5.6±1.7)×10^9/L,(108.6±9.5)U/L,(5.4±0.8)lg copies/ml,(4.6±0.9)lg IU/ml,(324.5±86.9)pg/ml,(3.2±0.6)mean fluorescene intendity(MFI)and(3.1±0.5)MFI in responders,significantly different as compared to(6.4±1.9)×10^9/L,(82.5±10.0)U/L,(6.1±0.9)lgcopies/ml,(5.8±1.1)lg IU/ml,(381.4±79.6)pg/ml,(3.8±0.7)MFI and(3.6±0.7)MFI in the non-responder group(P<0.05);multivariate Logistic regression analysis showed that serum HBV DNA loads,HBsAg,IP-10,IL-17A and IL-17F were the prognostic factors of response in patients with CHB treated withα-interferon(P<0.05).Conclusion Serum HBV DNA,HBsAg,IP-10 and Th-17 are the prognostic factors affecting the response in patients with CHB after treatment ofα-interferon,and detection of serum IP-10 and Th-17 might help predict the efficacy of peginterferon alfa-2b treatment.