广西地区HCV 1b型感染者NS5B区基因耐药多态性分析

阳光; 苏明华; 江建宁; 伍菲菲; 周奕; 张怀东; 李林蔓; 江梦凤; 黄锦妮; 梁丹丹

doi:10.3969/j.issn.1001-5256.2019.05.012

广西地区HCV 1b型感染者NS5B区基因耐药多态性分析

DOI: 10.3969/j.issn.1001-5256.2019.05.012

广西医科大学第一附属医院感染科

基金项目:

广西教育厅基金资助项目(YB2014064)；广西卫生厅基金资助项目(Z2011346)；广西南宁市青秀区科技局基金资助项目(2013ZH02)；

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中图分类号: R512.63
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出版历程
- 收稿日期: 2019-01-14
- 出版日期: 2019-05-20

Resistance-associated variants in the non-structural protein 5B region in patients with hepatitis C virus genotype 1b infection in Guangxi, China

Department of Infection Diseases, The First Affiliated Hospital of Guangxi Medical University

Research funding:

摘要

摘要: 目的分析我国广西地区HCV 1b型感染者NS5B区耐药基因相关变异（RAV）的发生率及不同性别间的差异。方法选取2016年4月-2018年9月广西医科大学第一附属医院收治的60例HCV 1b型感染初治患者,留取基线血清样本,采用巢式聚合酶链式反应扩增NS5B区片段并进行基因测序,测序结果与基因库标准株进行比对。不同性别患者间的年龄、HCV RNA、ALT和AST水平比较采用t检验,耐药位点变异率采用Fisher确切概率法检验。结果入选的60例患者中,55例获得完整的NS5B区序列信息,RAV发生率为96. 3%,其中C316 （94. 5%）、A338（70. 9%）、T19（74. 5%）为主要的变异位点,同时检测到C316+T19、C316+T19+A338等多位点联合突变。男性RAV发生率为95. 8%（23/24）,女性为96. 8%（30/31）,差异无统计学意义（P=1. 000）。结论广西地区HCV 1b型感染者NS5B区存在较高的RAV发生率,既有单位点突变,也存在多位点联合突变,且不同性别间RAV发生率无明显差异。
- 肝炎病毒属 /
- 肝炎,丙型 /
- 基因型 /
- 抗药性 /
- 横断面研究
Abstract: Objective To investigate the incidence rate of resistance-associated variants ( RAVs) in the non-structural protein 5B (NS5B) region in patients with hepatitis C virus ( HCV) genotype 1b ( GT1b) infection in Guangxi, China, as well as its difference between male and female patients. Methods A total of 60 previously untreated patients with HCV GT1b infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from April 2016 to September 2018 were enrolled. Their baseline serum samples were collected. The NS5B region fragments were amplified by nested PCR and gene sequencing was performed, and then the sequencing results were compared with standard strains in GeneBank. The t-test was used for comparison of age, HCV RNA, alanine aminotransferase ( ALT) , and aspartate aminotransferase ( AST) between male and female patients, and the Fisher's exact test was used for comparison of mutation rate of drug-resistance sites. Results Of all 60 patients, 55 obtained the complete sequence information of the NS5B region, and the incidence rate of RAVs in the NS5B region was 96. 3%. C316 ( 94. 5%) , A338 ( 70. 9%) , and T19 ( 74. 5%) were the main mutation sites, and multisite mutations such as C316 + T19 and C316 + T19 + A338 were observed. There was no significant difference in the incidence rate of RAVs between male patients and female patients [95. 8% ( 23/24) vs 96. 8% ( 30/31) , P = 1. 000]. Conclusion Patients with HCV GT1b infection in Guangxi have a high incidence rate of RAVs in the NS5B region, with both single-site and multisite mutations.There is no significant difference in the incidence rate of RAVs between male and female patients.
- hepacivirus /
- hepatitis C /
- genotype /
- drug resistance /
- cross-sectional studies

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参考文献(20)

[1] XIE L, HAO P, WU RH, et al. Establishment and application of a database for hepatitis C virus NS3/4A protease inhibitors and their drug resistance data[J]. J Clin Hepatol, 2018, 34 (9) :1884-1890. (in Chinese) 谢磊, 郝沛, 吴瑞红, 等. HCV NS3/4A蛋白酶抑制剂药物及其耐药信息数据库的建立和应用[J].临床肝胆杂志, 2018, 34 (9) :1884-1890.

[2] MESSINA JP, HUMPHREYS I, FLAXMAN A, et al. Global distribution and prevalence of hepatitis C virus genotypes[J].Hepatology, 2015, 61 (1) :77-87.

[3] PAWLOTSKY JM, NEGRO F, AGHEMO A, et al. EASL Recommendations on treatment of hepatitis C 2018[J]. Hepatology, 2018, 69 (2) :461-511.

[4] MOHD HANAFIA K, GROEGER J, FLAXMAN AD, et al. Global epidemiology of hepatitis C virus infection:New estimates of age-specific antibody to HCV seroprevalence[J]. Hepatology, 2013, 57 (4) :1333-1342.

[5] TANG W, SU MH, JIANG JN, et al. Epidemiological characteristics and genotype distribution of hepatitis C virus in Guangxi[J]. World Chin J Dig, 2014, 22 (9) :1300-1306. (in Chinese) 唐维, 苏明华, 江建宁, 等.广西地区丙型肝炎病毒的基因型分布与流行病学特征[J].世界华人消化杂志, 2014, 22 (9) :1300-1306.

[6] MANNS M, MARCELLIN P, POORDAD F, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1infection (QUEST-2) :A randomised, double-blind, placebo-controlled phase 3 trial[J]. Lancet, 2014, 384 (9941) :414-426.

[7] DONALDSON EF, HARRINGTON PR, O'REAR JJ, et al. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir[J]. Hepatology, 2015, 61 (1) :56-65.

[8] QUAN M, XING HC. Effects of hepatitis C virus resistance associated variants on the efficacy of direct-acting antiviral agents[J/CD]. Chin J Liver Dis:Electronic Edit, 2018, 10 (3) :32-36. (in Chinese) 全敏, 邢卉春.丙型肝炎病毒耐药相关变异对直接抗病毒药物疗效的影响[J/CD].中国肝脏病杂志:电子版, 2018, 10 (3) :32-36.

[9] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guide line of prevention and treatment for chronic hepatitis C:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1961-1979. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.丙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1961-1979.

[10] AN ZY, DING Y, DOU XG, et al. Selection and evaluation of treatment regimens with direct-acting antiviral agents for patients with chronic hepatitis C in the real world in China[J]. J Clin Hepatol, 2018, 34 (2) :233-237. (in Chinese) 安子英, 丁洋, 窦晓光, 等.我国慢性丙型肝炎患者真实世界中直接抗病毒药物治疗方案的选择与评价[J].临床肝胆杂志, 2018, 34 (2) :233-237.

[11] LEMM JA, LIU M, GENTLES RG, et al. Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis C Virus NS5B polymerase[J]. Antimicrob Agents Chemother, 2014, 58 (6) :3485-3495.

[12] DVORY-SOBOL H, VOITENLEITNER C, MABERY E, et al.Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase[J]. Antimicrob Agents Chemother, 2014, 58 (11) :6599-6606.

[13] SUN D, DAI M, SHEN S, et al. Analysis of naturally occurring resistance-associated variants to NS3/4A Protein inhibitors, NS5A protein inhibitors, and NS5B polymerase inhibitors in patients with chronic hepatitis C[J]. Gene Expression, 2018, 18 (1) :63-69.

[14] CHARLTON M, GANE E, MANNS MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation[J]. Gastroenterology, 2015, 148 (1) :108-117.

[15] ALVES R, QUEIROZ ATL, PESSOA MG, et al. The presence of resistance mutations to protease and polymerase inhibitors in hepatitis C virus sequences from the Los Alamosdatabank[J]. J Viral Hepat, 2013, 20 (6) :414-421.

[16] WANG Y, RAO HY, XIE XW, et al. Direct-acting antiviral agents resistance-associated polymorphisms in chinese treatment-nave patients infected with genotype 1b hepatitis C virus[J]. Chin Med J (Engl) , 2015, 128 (19) :2625-2631.

[17] JI H, KOZAK RA, BIONDI MJ, et al. Next generation sequencing of the hepatitis C virus NS5B gene reveals potential novel S282drug resistance mutations[J]. Virology, 2015, 477:1-9.

[18] BARTELS DJ, SULLIVAN JC, ZHANG EZ, et al. Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment[J]. J Virol, 2013, 87 (3) :1544-1553.

[19] HALFON P, SARRAZIN C. Future treatment of chronic hepatitis C with direct acting antivirals:Is resistance important?[J].Liver Int, 2012, 32 (Suppl 1) :79-87.

[20] VOITENLEITNER C, CROSBY R, WALKER J, et al. In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor[J]. Antimicrob Agents Chemother, 2013, 57 (11) :5216-5224.

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