Natural resistance mutations to direct- acting antiviral agents in interferon / ribavirin treatment- experienced and treatment- nave patients with chronic hepatitis C in Beijing,China

Objective To investigate the incidence of natural resistance mutations to direct- acting antiviral agents( DAAs) in patients with chronic hepatitis C( CHC) in Beijing,China,and to compare the natural resistance mutations to DAAs in interferon( IFN) / ribavirin( RBV) treatment- experienced and treatment- nave patients. Methods A total of 101 CHC patients with genotype 1b who visited Peking University First Hospital from July 2009 to November 2013 were enrolled,among whom 40 patients were once treated with IFN / RBV and 61 patients were not treated with IFN / RBV. The patients' HCV RNA was extracted,and polymerase chain reaction was applied for amplification. The genes in HCV NS3,NS5 A,and NS5 B regions were sequenced,sequence alignment and resistance analysis were performed,and the incidence of natural resistance was compared. The t- test was applied for comparison of normally distributed continuous data between groups,and the Mann- Whitney U rank sum test was applied for comparison of abnormally distributed continuous data between groups. The chi- square test or Fisher 's exact test was applied for comparison of categorical data between groups. Results The sequences of NS3,NS5 A,and NS5 B regions were obtained from 84( 83. 17%),92( 91. 09%),and 97( 96. 04%) patients,respectively. The natural resistance mutations to DAAs in NS3 region occurred in 7 patients( 8. 33%)( T54 S,n = 1,1. 19%; R117 H,n = 5,5. 95%; N174 F,n = 1,1. 19%),those in NS5 A region occurred in 19 patients( 20. 65%)( L28 M,n = 7,7. 61%; L31 M,n = 1,1. 09%; P58 S,n = 4,4. 35%; Y93 H,n = 7,7. 61%),and those in NS5 B region occurred in 95 patients( 97. 94%)( L159 F,n = 1,1. 03%; C316 N,n = 92,94. 85%; A421 V,n = 6,6. 18%; R422 K,n = 1,1. 03%; M426 L,n = 3,3. 09%; V499 A,n = 38,39. 18%). The incidence of resistance mutations to DAAs in NS3,NS5 A,and NS5 B regions showed no significant difference between the IFN / RBV treatment- experienced and treatment- nave patients( all P > 0. 05). Conclusion Natural resistance mutations to DAAs exist in the treatment- nave CHC patients with genotype 1b in Beijing. Most of these mutations are low resistance mutations,and their effects on the clinical efficacy of DAAs need further investigation. The association between IFN / RBV treatment and increased natural resistance mutations to DAAs was not observed in CHC patients.