CAJ | 학술논문

目的：分析基因1b 型慢性丙型肝炎（CHC）复发型的患者再次进行聚乙二醇干扰素（peg-IFN）联合利巴韦林（RBV）治疗时的病毒学应答情况，探讨 IL-28B rs12978960基因多态性对再治疗患者病毒应答及疗效的影响。方法对河南省人民医院感染性疾病科2012年至2014年收治的CHC 复发患者采用 peg-IFN 联合 RBV 治疗48周并随访24周，检测宿主 IL-28B rs12978960基因的多态性，分析患者抗病毒治疗的病毒学应答情况，以及与持续病毒学应答（SVR）相关的预测因素。计量资料采用独立样本 t 检验，计数资料采用χ2检验或 Fisher 确切概率法。结果61例患者完成 peg-IFN联合 RBV 治疗48周并随访24周，平均年龄（46．7±12．4）岁，男37例（60．7％），rs12978960 CC 基因型49例（80．3％）。经过 peg-IFN／RBV 治疗48周并随访24周后，达到 SVR 者40例（65．6％）。年轻患者能获得较高的快速病毒学应答（RVR）率和 SVR 率，差异均有统计学意义（均 P ＜0．05）；IL-28B rs12978960基因型对 RVR 和 SVR 有预测价值，获得 RVR 和 SVR 的患者 CC 基因型携带率更高（均P ＜0．05）。CC 基因型相对于 CT／TT 型的患者可获得较高的 RVR （34．1％比0，χ2＝10．625，P ＝0．006）、治疗结束时病毒学应答（84．1％比70．6％，χ2＝5．563，P ＝0．039）和 SVR（77．3％比35．3％，χ2＝9．572，P ＝0．007），而延长快速病毒学应答（34．1％比29．4％，χ2＝0．122，P ＝0．809）、早期病毒学应答（79．5％比82．3％，χ2＝0．612，P ＝0．964）与 CT／TT 基因型患者之间差异无统计学意义。结论基因1b 型 CHC 复发患者仍需再次抗病毒治疗。IL-28B rs12978960基因多态性与再治疗 SVR 率密切相关，尤其是对未获得 RVR 的患者更具预测价值，为 CHC 患者个体化抗病毒治疗和优化诊疗方案提供了有利依据。
목적：분석기인1b 형만성병형간염（CHC）복발형적환자재차진행취을이순간우소（peg-IFN）연합리파위림（RBV）치료시적병독학응답정황，탐토 IL-28B rs12978960기인다태성대재치료환자병독응답급료효적영향。방법대하남성인민의원감염성질병과2012년지2014년수치적CHC 복발환자채용 peg-IFN 연합 RBV 치료48주병수방24주，검측숙주 IL-28B rs12978960기인적다태성，분석환자항병독치료적병독학응답정황，이급여지속병독학응답（SVR）상관적예측인소。계량자료채용독립양본 t 검험，계수자료채용χ2검험혹 Fisher 학절개솔법。결과61례환자완성 peg-IFN연합 RBV 치료48주병수방24주，평균년령（46．7±12．4）세，남37례（60．7％），rs12978960 CC 기인형49례（80．3％）。경과 peg-IFN／RBV 치료48주병수방24주후，체도 SVR 자40례（65．6％）。년경환자능획득교고적쾌속병독학응답（RVR）솔화 SVR 솔，차이균유통계학의의（균 P ＜0．05）；IL-28B rs12978960기인형대 RVR 화 SVR 유예측개치，획득 RVR 화 SVR 적환자 CC 기인형휴대솔경고（균P ＜0．05）。CC 기인형상대우 CT／TT 형적환자가획득교고적 RVR （34．1％비0，χ2＝10．625，P ＝0．006）、치료결속시병독학응답（84．1％비70．6％，χ2＝5．563，P ＝0．039）화 SVR（77．3％비35．3％，χ2＝9．572，P ＝0．007），이연장쾌속병독학응답（34．1％비29．4％，χ2＝0．122，P ＝0．809）、조기병독학응답（79．5％비82．3％，χ2＝0．612，P ＝0．964）여 CT／TT 기인형환자지간차이무통계학의의。결론기인1b 형 CHC 복발환자잉수재차항병독치료。IL-28B rs12978960기인다태성여재치료 SVR 솔밀절상관，우기시대미획득 RVR 적환자경구예측개치，위 CHC 환자개체화항병독치료화우화진료방안제공료유리의거。
Objective To investigate the virological response in hepatitis C virus (HCV)genotype 1b relapsers after 48 weeks of peginterferon/ribavirin (peg-IFN/RBV)combination retreatment,and to explore the predictive value of interleukin (IL )-28B rs12978960 genetic polymorphismon virological response.Methods From 2012 to 2014,genotype 1b chronic hepatitis C (CHC)relapsers in He′nan Provincial People′s Hospital were retreated with combined peg-IFN/RBV for 48 weeks and followed up for 24 weeks off-treatment.Host IL-28B genetic polymorphism was detected.Predictive factors associated with virological response and sustained virological response (SVR)were analyzed.Independent-samples t test was conducted in continuous variables,whileχ2 test or Fisher exact probability test was conducted in counts data.Results A total of 61 patients finished 48 weeks of peg-IFN/RBV combination therapy and were further followed up for 24 weeks off-treatment.Mean age was (46.7 ±12.4)years.Thirty-seven patients (60.7%)were male and 49 were rs12978960 CC genotype.After 48 weeks of retreatment with peg-IFN/RBV and 24 weeks of off-treatment follow-up,40 patients (65 .6%)achieved SVR.Rapid virological response (RVR)and SVR of younger patients were both significantly higher than those of older patients (100.0% vs 67.4% and 85 .0% vs 47.6%,respectively;both P =0.006).IL-28B rs12978960 genotype was predictive to RVR and SVR.Patients with RVR and SVR had higher carriage rates of IL-28B rs12978960 CC genotype compared with those without RVR and SVR (both P <0.05 ).Patients with CC genotype had higher rates of RVR (34.1 % vs 0;χ2 = 10.625 ,P =0.006 ),end-of-treatment virological response (84.1 % vs 70.6%;χ2 =5 .563,P =0.039 )and SVR (77.3% vs 35 .3%;χ2 =9.572,P =0.007)than those with CT/TT genotype.However,there were no statistical differences of extended RVR (34.1 % vs 29.4%;χ2 =0.122,P =0.809)and early virological response (79.5 % vs 82.3%;χ2 =0.612,P =0.964).Conclusions Retreatment with antiviral therapy is necessary in CHC patients with genotype 1b. IL-28B rs12978960 genetic polymorphism is predictive to the SVR of retreatment,especially for patients without RVR,which will provide individualized treatment and optimize the treatment strategy.