广西地区HCV 1b型感染者NS5B区基因耐药多态性分析

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

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。

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.