| Objective: To investigate the incidence of natural resistance mutations to NS5 A inhibitors in patients with chronic hepatitis C without antiviral therapy.Methods:(1)Collected the 233 patients’ peripheral venous blood before treatment,and send the sample to Wuhan Kang Shengda Medical Inspection Center to detect genotypes;(2)The patients’ HCV RNA was extracted,and nested PCR was carried out by designing specific primers for the associated drug resistance sites of NS5 A region;(3)The PCR products were sequenced by Sangon Biotech(Shanghai)Co.,Ltd,the sequencing results were compared with the gene library sequences,the resistance analysis were performed and resistance mutation sites were identified.Results:(1)A total of 214 cases of 233 patients were successfully ampl ified and sequenced,among them,191 cases of chronic hepatitis C,23 ca ses of hepatitis C cirrhosis.There were 19 cases of genotype 1a,100 cas es of genotype 1b,23 cases of genotype 3a,30 cases of genotype 3b an d 42 cases of genotype 6a;(2)Of Which 76cases(35.5%)were detected mutation sites,there were 56 cases(26.2%)existed the single drug resistance sites and 20 cases(9.3%)existed two drug resistance sites combined;(3)Of which 119 cases were genotype 1,there were 53 patients(25.7%)existed the associated drug resistance mutation in genotype 1.There were7 cases(36.9%)with related resistance mutations in genotype 1a: Q30H(n=1,5.3%),H58P(n=1,5.3%),M28T+H58P(n=1,5.3%)和 H58P+E62D(n=4,21.0%);there were 46 cases(46.0%)existed the related resistance mutations in genotype 1b: R30Q(n=23,23.0%),Y93H(n=6,6.0%),Q54H(n=5,5.0%),P58S(n=4,4.0%),Q54H+P58S(n=4,4.0%),L31M+R30Q(n=2,2.0%)and Q54H+ R30Q(n=2,2.0%);(4)Of which 53 cases were genotype 3,there were 19 patients(35.8%)existed the associated drug resistance mutation.Among them,9 cases(39.1%)existed the related resistance mutations in genotype3a: A30K(n=2,8.7 %),L31M(n=1,4.3%)and A30K+L31M(n=6,21.0%);there were 10 cases(33.3%)existed the related resistance mutations in genotype 3b:M28L(n=1,3.3%),K30A(n=1,3.3%),M31L(n=3,10.0%),T54A(n=4,13.4%)and K30A+M31L(n=1,3.3%);(5)Of which 42 cases were genotype6 a,there were 3patients(7.2%)existed the associated drugresistance mut ation:F28V(n=1,2.4%),T58P(n=1,2.4%)and T93A(n=1,2.4%);(6)The mutat ion rate of each genotype was compared: the genotype 1 and genotype 3 were compared(44.5% VS 35.8%),P=0.286>0.05,the difference was not statistically significant;the genotype 1 and genotype 6 were compared(44.5% VS 7.2%),P=0.000<0.05,the difference was statistically significant;t he genotype 3 and genotype 6 were compared(35.8%VS 7.2%),P = 0.001 <0.05,the difference was statistically significant.(7)The mutation rate of hepatitis C cirrhosis and chronic hepatitis C patientswere compared(47.8% VS 34.0%),P=0.000<0.05,the difference was statistically significant.Conclusions:(1)Naturally drug resistant mutations in NS5 A inhibitors existed in patients with untreated chronic hepatitis C in Guangxi,there was not only a single drug resistance sites but also two drug resistance sites combined;(2)The mutation rate of patients with genotype 1 and 3 was higher than that with genotype 6;(3)The mutation rate of patients with hepatitis C cirrhosis was higher than that of patients with chronic hepatitis Cand the rate of drug resistance mutation may be related to the occurrence of liver cirrhosis. |
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