河南地区丙型肝炎病毒1b亚型ISDR变异对聚乙二醇干扰素联合利巴韦林抗病毒疗效的影响因素分析  

Impact of mutation in inferferon sensitivity determing region on the efficacy of the combined pegylated interferon/ribavirin therapy in Henan patients with chronic hepatitis C virus genotype 1b infection

作　　者：魏君锋[1] 曾艳丽[1] 李宽[1] 肖二辉[1] 刘俊平[1] 丁岗强[1] 康谊[1] 尚佳[1] 

机构地区：[1]郑州大学人民医院河南省人民医院感染性疾病科,郑州450003

出　　处：《中华实用诊断与治疗杂志》2016年第9期883-886,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省医学科技攻关项目(201203123);河南省教育厅科学技术研究重点项目(14A320054);国家临床重点专科建设项目(2013年度)

摘　　要：目的探讨河南地区丙型肝炎病毒（hepatitis C virus，HCV）lb亚型干扰素敏感决定区（ interferon sensitivitydetermining region, ISDR）氨基酸序列变异是否影响聚乙二醇干扰素（pegylated interferon, PEG-IFN）联合利巴韦林（ribavirin，RBV）治疗慢性丙型肝炎（chronichepatitisC，CHC）的抗病毒疗效，评价其预测价值。方法对49例HCV1b亚型慢性感染者采用PEG-IFN／RBV联合方案治疗48周，并随访24周。定量检测血清HCV—RNA，RT—PCR扩增治疗前血清标本中HCV—ISDR片段并测序，MEGA4分析氨基酸序列变异度；二分类logistic回归分析各变量与持续病毒学应答（sustained virological response, SVR）之间的关系。结果SVR率为69．4％（34／49）；治疗前血清HCV的ISDR氨基酸序列与HCVJ株比较，12例为野生型（未突变），36例为中间型（1～3个突变），1例为突变型（≥4个突变）；二分类logistic回归分析显示，影响SVR的主要因素是ISDR氨基酸残基突变（OR=21．505，P=0．001），其次是年龄（OR=0．876，P=0．042）；ISDR氨基酸突变数≥2个的CHC组所获得的SVR（13／14）明显高于氨基酸突变数〈2个的CHC组（1／15）（P〈0．05），年龄≤40岁者SVR（14／I7）高于年龄〉40岁者（20／32）（P〈0．05）。结论河南地区HCV1b亚型ISDR突变型极少；PEG-IFN／RBV联合方案治疗中，对SVR有预测价值的为ISDR氨基酸突变数≥2个和年龄≤40岁。Objective To investigate the impact of aminoacid variation in interferon sensitivity determining region （ISDR） on the efficacy of pegylated interferon plus ribavirin （PEG-IFN/RBV） therapy on chronic hepatitis C（CHC） in patients with hepatitis C virus （HCV） genotype lb infection in Henan, and evaluate its predictive value. Methods A total of 49 patients with HCV genotype 1b infection were treated by Peg-IFN/RBV for 48 weeks and were followed up for 24 weeks. The serum HCV RNA was quantitatively analyzed. HCV ISDR was proliferated by RT-PCR technique before treatment and was sequenced. Alignment and analysis of aminoacid sequences were carried out with MEGA 4 software. Binary logistic regression was performed to analyze the correlations between variables and sustained virological response （SVR）. Results SVR rate was 69.4% （34/49）. Among 49 samples, there were 12 cases of wild type （no aminoacid mutation）, 36 of intermediate type （1 to 3 aminoacid mutations） and only 1 of mutant type （≥4 aminoacid mutations） when compared with HCV J strain. Binary logistic regression analysis showed that ISDR mutation （≥2） （OR=21. 505, P=0. 001） and age （OR= 0. 876, P= 0. 042） were the main influencing factors for SVR. The SVR was significantly higher in CHC patients with ≥2 aminoacid mutations in ISDR （13/14） than that in CHC patients with 〈2 aminoacid mutations （1/15） （P〈0.05）, and higher in ≤40-year-old patients （14/17） than that in 〉40-year-old patients （20/32）（P〈0.05）. Conclusion The mutant type of ISDR （≥4） is rare in Henan. ISDR aminoacidmutation ≥2 and age≤40 years can be used to predict SVR in PEG-IFN/RBV combination therapy for CHC patients.

关 键 词：慢性丙型肝炎 干扰素敏感决定区 聚乙二醇干扰素 利巴韦林 持续病毒学应答 

分 类 号：R512.63[医药卫生—内科学]