Li Zhanyi, Zhang Ying, Liu Ying, Shao Xiaoqiong, Luo QiuMin, Cai Qingxian, Zhao Zhixin
Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, Guangdong, China.
Medicine (Baltimore). 2017 May;96(19):e6830. doi: 10.1097/MD.0000000000006830.
The direct-acting antiviral agents (DAAs) have drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the resistance-associated variants (RAVs) to DAAs may hamper treatment. There was a lack of data on the prevalence of pre-exist RAVs in Chinese HCV-infected patients. We performed nested PCR assays on 74 HCV genotype 1b-infected patients to amplify HCV viral regions of NS3, NS5A, and NS5B to investigate the prevalence of RAVs to DAAs in treatment-naive HCV genotype1b-infected patients in China. The mutations A156S, T54S, and D168Y of the NS3/4A region were found in 18.33% (11/60), 6.67% (4/60), and 1.67% (1/60) of the successfully amplified cases. Mutations Q30R, L31M, and H58P of the NS5A region were confirmed in 57.63% (34/59), 1.69%(1/59), and 86.44% (51/59) of the cases. Mutations C316N, S365A, M414L, M423I, Y448H, I482T, I482 V, V494L, P495S, and V499A of the NS5B region were detected in 100% (60/60), 3.33% (2/60), 5.88% (3/51), 1.96% (1/51), 1.96% (1/51), 5.88% (3/51), 1.96% (1/51), 3.92% (2/51), 5.88% (3/51), and 15.69% (8/51) of cases, respectively. Naturally occurring RAVs to DAAs pre-exist in treatment-naive Chinese HCV genotype 1b-infected patients and the characteristic is different from that in Europe and the United States. Clinicians should consider RAVs upon the introduction of DAA-based antiviral therapy.
直接抗病毒药物（DAAs）极大地改善了丙型肝炎病毒（HCV）患者的预后。然而，对DAAs的耐药相关变异（RAVs）可能会妨碍治疗。在中国HCV感染患者中，关于预先存在的RAVs流行情况的数据尚缺乏。我们对74例HCV基因1b型感染患者进行了巢式PCR检测，以扩增NS3、NS5A和NS5B的HCV病毒区域，从而调查中国初治HCV基因1b型感染患者中对DAAs的RAVs流行情况。在成功扩增的病例中，NS3/4A区域的A156S、T54S和D168Y突变分别在18.33%（11/60）、6.67%（4/60）和1.67%（1/60）的病例中被发现。NS5A区域的Q30R、L31M和H58P突变分别在57.63%（34/59）、1.69%（1/59）和86.44%（51/59）的病例中得到确认。NS5B区域的C316N、S365A、M414L、M423I、Y448H、I482T、I482V、V494L、P495S和V499A突变分别在100%（60/60）、3.33%（2/60）、5.88%（3/51）、1.96%（1/51）、1.96%（1/51）、5.88%（3/51）、1.96%（1/51）、3.92%（2/51）、5.88%（3/51）和15.69%（8/51）的病例中被检测到。在中国初治的HCV基因1b型感染患者中预先存在对DAAs的自然发生的RAVs，其特征与欧美地区不同。临床医生在引入基于DAA的抗病毒治疗时应考虑RAVs。
