北京地区干扰素联合利巴韦林经治与未经治慢性丙型肝炎患者直接抗病毒药物的天然耐药突变分析

张玉; 曹颖; 张仁雯; 张霞霞; 陆海英; 吴赤红; 霍娜; 于敏; 刘丹; 徐小元

doi:10.3969/j.issn.1001-5256.2016.04.020

北京地区干扰素联合利巴韦林经治与未经治慢性丙型肝炎患者直接抗病毒药物的天然耐药突变分析

DOI: 10.3969/j.issn.1001-5256.2016.04.020

北京大学第一医院肝病科

基金项目:

国家“十二五”重大科技专项资助项目(2012ZX10002003-004-003)；国家自然科学基金资助项目(81373056)；

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中图分类号: R512.63
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出版历程
- 出版日期: 2016-04-20

Natural resistance mutations to direct- acting antiviral agents in interferon / ribavirin treatment- experienced and treatment- nave patients with chronic hepatitis C in Beijing,China

Peking University First Hospital

Research funding:

摘要

摘要:
目的探索我国北京地区慢性丙型肝炎（CHC）患者直接抗病毒药物（DAA）的天然耐药突变发生情况,比较干扰素（IFN）联合利巴韦林（RBV）经治与未经治患者DAA的天然耐药突变。方法收集2009年7月-2013年11月于北京大学第一医院就诊的101例基因1b型CHC患者,其中IFN联合RBV经治患者40例,未经治患者61例。提取患者的HCV RNA,PCR法扩增并测序HCV NS3、NS5A、NS5B区基因,进行序列比对和耐药分析,并比较天然耐药发生率。符合正态分布的计量资料组间比较采用t检验,非正态分布的计量资料组间差异比较采用Mann-Whitney U检验。计数资料组间比较采用χ2检验或Fisher精确概率法。结果共获得84例（83.17%）NS3区、92例（91.09%）NS5A区和97例（96.04%）NS5B区基因序列信息。NS3区7例（8.33%）存在DAA天然耐药突变（T54S,n=1,1.19%;R117H,n=5,5.95%;N174F,n=1,1.19%）。NS5A区19例（20.65%）存在天然耐药突变（L28M,n=7,...
- 肝炎,丙型,慢性 /
- 抗病毒药 /
- 抗药性,病毒 /
- 干扰素类 /
- 利巴韦林 /
- 北京
Abstract:
Objective To investigate the incidence of natural resistance mutations to direct- acting antiviral agents( DAAs) in patients with chronic hepatitis C( CHC) in Beijing,China,and to compare the natural resistance mutations to DAAs in interferon( IFN) / ribavirin( RBV) treatment- experienced and treatment- nave patients. Methods A total of 101 CHC patients with genotype 1b who visited Peking University First Hospital from July 2009 to November 2013 were enrolled,among whom 40 patients were once treated with IFN / RBV and 61 patients were not treated with IFN / RBV. The patients' HCV RNA was extracted,and polymerase chain reaction was applied for amplification. The genes in HCV NS3,NS5 A,and NS5 B regions were sequenced,sequence alignment and resistance analysis were performed,and the incidence of natural resistance was compared. The t- test was applied for comparison of normally distributed continuous data between groups,and the Mann- Whitney U rank sum test was applied for comparison of abnormally distributed continuous data between groups. The chi- square test or Fisher 's exact test was applied for comparison of categorical data between groups. Results The sequences of NS3,NS5 A,and NS5 B regions were obtained from 84( 83. 17%),92( 91. 09%),and 97( 96. 04%) patients,respectively. The natural resistance mutations to DAAs in NS3 region occurred in 7 patients( 8. 33%)( T54 S,n = 1,1. 19%; R117 H,n = 5,5. 95%; N174 F,n = 1,1. 19%),those in NS5 A region occurred in 19 patients( 20. 65%)( L28 M,n = 7,7. 61%; L31 M,n = 1,1. 09%; P58 S,n = 4,4. 35%; Y93 H,n = 7,7. 61%),and those in NS5 B region occurred in 95 patients( 97. 94%)( L159 F,n = 1,1. 03%; C316 N,n = 92,94. 85%; A421 V,n = 6,6. 18%; R422 K,n = 1,1. 03%; M426 L,n = 3,3. 09%; V499 A,n = 38,39. 18%). The incidence of resistance mutations to DAAs in NS3,NS5 A,and NS5 B regions showed no significant difference between the IFN / RBV treatment- experienced and treatment- nave patients( all P > 0. 05). Conclusion Natural resistance mutations to DAAs exist in the treatment- nave CHC patients with genotype 1b in Beijing. Most of these mutations are low resistance mutations,and their effects on the clinical efficacy of DAAs need further investigation. The association between IFN / RBV treatment and increased natural resistance mutations to DAAs was not observed in CHC patients.
- hepatitis C,chronic /
- antiviral agents /
- drug resistance,viral /
- interferons /
- ribavirin /
- BEIJING

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