Liu Grey, Cai Qingxian, Li Zhanyi, Shao Xiaoqiong, Luo Qiumin, Zhang Xiaohong, Zhao Zhixin
The Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Antivir Ther. 2016;21(5):369-75. doi: 10.3851/IMP2852. Epub 2014 Sep 15.
Gene polymorphism of HCV is an important cause of drug resistance to direct-acting antivirals (DAAs).
Nested PCR assays were performed to amplify the HCV viral regions of NS3, NS5A and NS5B.
Major resistant mutation A156S was found in 18.33% of patients with HCV-1b and 64.28% of patients with HCV-2a. HCV-6a patients had a Q80K mutation rate of 95.45%, while the mutation rate of V170I was up to 100%. Mutation frequency varied with the different genotypes of HCV. The proportion of four resistance mutations (M36L, Q80K, A156S, V170I) in different groups were statistically significant (P<0.05). Resistant mutation Q30R was detected in 116 (72.5%) samples with HCV-1b and -6a, L31M was found in 16 patients, including 12 with HCV-2a and 4 with HCV-6a, H58P was discovered in 42.5% (68/160) of patients with the genotypes Q30R, L31M and H58P; Y93C was found in 9individuals with only HCV-2a. In HCV NS5B sequences, only a few resistant variants were detected, including C316N and S282T.
Naturally occurring dominant resistance mutations to HCV DAAs pre-existed in treatment-naive patients in China. Mutation frequency and characteristics varied with the HCV genotype.
丙型肝炎病毒（HCV）基因多态性是导致直接作用抗病毒药物（DAA）耐药的重要原因。
采用巢式聚合酶链反应（PCR）检测HCV NS3、NS5A和NS5B病毒区域。
在HCV-1b患者中，18.33%发现主要耐药突变A156S；在HCV-2a患者中，64.28%发现该突变。HCV-6a患者Q80K突变率为95.45%，而V170I突变率高达100%。突变频率因HCV基因型不同而异。不同组中四种耐药突变（M36L、Q80K、A156S、V170I）的比例具有统计学意义（P<0.05）。在116份（72.5%）HCV-1b和-6a样本中检测到耐药突变Q30R；16例患者中发现L31M突变，其中12例为HCV-2a，4例为HCV-6a；在Q30R、L31M和H58P基因型患者中，42.5%（68/160）发现H58P突变；仅在9例HCV-2a患者中发现Y93C突变。在HCV NS5B序列中，仅检测到少数耐药变异，包括C316N和S282T。
在中国，初治患者中已存在对HCV DAA的自然发生的主要耐药突变。突变频率和特征因HCV基因型而异。
