| Objective: To analyze the incidence of resistance associated variants(RAVs)and the differences between the sexes in the NS5 B region for patients with different HCV genotypes in guangxi,China.Methods: 135 patients with HCV infection and confirmed genotype in the first affiliated hospital of guangxi medical university were studied.Baseline serum samples were collected and serum samples from 2 patients without SVR after DAAs treatment were collected.HCV RNA was extracted from the patients.Specific primers for HCV NS5 B region were designed for nested PCR amplification,the obtained products were sent to Shanghai sangon biotechnology co.,ltd.for gene sequencing in NS5 B region.The sequencing results were compared with the standard strains in the gene bank to analyze the drug-resistant mutations,and the drug-resistant mutations of 2 patients without SVR before and after treatment were compared.To patient's age betweendifferent gender,HCV RNA,ALT and AST by using two independent samples t test,the resistance locus mutation rates between different gender patients with single factor analysis of variance,the classification of data by chi-square test,measurement data with mean + /-standard deviation,said count data using percentage said,P < 0.05 for the difference was statistically significant.Results:(1)among the 135 patients,126 obtained complete NS5 B sequence information,including 103 patients with chronic hepatitis c and 23 patients with hepatitis c cirrhosis,including 55 patients with GT1 b,13 patients with GT3 a,20patients with GT3 b and 38 patients with GT6 a.(2)the incidence of RAV in NS5 B region in 126 patients with successful amplification was 46%(58/126),in which the unit point mutation rate was 15.1%(19/126)and the multilocus associated mutation rate was 30.9%(39/126).(3)the incidence of RAVs in the NS5 B region of 55 patients with genotype 1b was 96.3%(53/55),among which C316 was 94.5%(52/55),A338 70.9%(49/55)and T19 74.5%(41/55)were the main mutation loci.No relevant mutation sites were detected in patients with genotype 3a.The incidence of RAVs in NS5 B region was 80%(16/20)in 20 patients with gene type 3b,and A421 V was the main mutation site.The incidence of RAVs in the NS5 B region of 38 patients with gene 6a type was7.9%(3/38),and V494 A was the detected mutation site.(6)pairwise comparison of mutation rates of all genotypes: compared with the mutation rates of GT1 and GT3 genotypes(96.% vs 6.1%),P<0.05,and the difference was statistically significant.Compared with the mutation rate of GT1 type and GT6 type(96.4%vs 7.9%),P<0.05,and the difference was statistically significant.Compared with the mutation rate of GT3 type and GT6 type(6.1% vs 7.9%),P>0.05,and the difference was no statistically significant.(7)there was no significant difference in age,HCVRNA,AST and ALT between the two sexes(all P>0.05).The incidence of RAVs in males was 60.6%(40/66)and in females 58.3%(35/60),with no statistically significant difference(P>0.05).(8)the drug resistance mutation rate of patients with chronic hepatitis c and cirrhosis was78.3%(18/23),higher than 55.3%(57/103)of patients with chronic hepatitis C,P<0.05,and the difference was statistically significant.Conclusion: patients with newly diagnosed chronic hepatitis c in guangxi have a higher incidence of RAV mutation in NS5 B region,which includes both unit point mutation and two-site association mutation,and even multi-site association mutation in patients with GT1 b.The main drug-resistant mutation locus of gene 1b patients was C316 N ? A338 V and V321 I.The main drug-resistant mutation locus of genotype 3a was not detected in our study.The main drug-resistant mutation locus of gene 3b was E237 G.The main drug-resistant mutation locus of gene 6a was A421 V.Multilocus associated mutations was C316N+T19S ? C316N+V321I ? C316N+T19S+A338V and occur mainly in patients with GT1 b.The rate of drug resistance related variation in patients with chronic hepatitis c and cirrhosis was higher than that in patients with chronic hepatitis c.There was no significant difference in the rate of variation associated with baseline drug resistance between the sexes. |
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