The Prevalence Of Pre-existing HCV Variants Resistant To Direct-acting Antiviralagents And Epidemiology And Treatment Of HCV Infection

Objective:Recently,the World Health Organization(WHO)adopted the first-ever global hepatitis strategy with the goal of eliminating viral hepatitis as a public health threat by 2030.Direct-acting antiviral agents(DAAs)open a whole new era for anti-HCV therapy,in this regard,it seems more feasible to achieve the goal with respect to HCV infection.However,DAA resistance associated variants(RAVs)could jeopardize the effectiveness of DAAs.And the global prevalence of DAA RAVs remains unknown.In addition,China has a heavy burden of viral hepatitis,but the epidemiology and treatment of HCV infection in Western China are still unknown.Therefore,it is necessary to have a clear understanding on problems mentioned above,so that we can realize the ambitious goals proposed by WHO earlier.Methods:1.Global prevalence of pre-existing HCV variants resistant todirect-acting antiviral agents: HCV genome sequences were obtained from NCBI nucleotide database.RAVs were summarized from related literatures.Sequences were aligned and analyzed by MEGA 5.0.Statistical analysis were conducted by SPSS 20.0.2.Epidemiology and treatment of HCV infection in Western China:We retrospectively analyzed electronic medical records data from patients who underwent the HCV-antibody(HCV-Ab)test in our hospital between2013 and 2015.The positivity of HCV-Ab and HCV-RNA and the treatment of HCV-RNA positive patients were evaluated.Results:1.In total,58.7% of sequences(854/1455)harbored at least one dominant resistance variant and the highest RAV frequency occurred in Asia(74.1%),followed by Africa(71.9%),America(53.5%)and Europe(51.4%).The highest RAV frequency was observed in genotype(GT)6sequences(99%),followed by GT2(87.9%),GT4(85.5%),GT1a(56%),GT3(50.0%)and GT1b(34.3%).Furthermore,40.0% and 29.6% of sequences were detected RAVs to non-structural(NS)5A inhibitors and NS3 protease inhibitors respectively.However,RAVs to NS5 B nucleotide inhibitor(NI)and NI-based combinations were uncommon(< 4% of sequences).As expected,combinations of multiple RAVs to the IFN-free regimens recommended by current guidelines were rarely detected(0.2% to2.0%).2.A total 112576 individuals were enrolled for this analysis.The overall positive rate of HCV-Ab was 1·44%(1616/112576),and it was higher in males than females(1·96% vs.1·06%,p<0·01).The HCV-Ab prevalence was mainly presented in the 35-44 age group(3·24%,591/18254).The prevalence of HCV-Ab in patients from a department of non-infectious diseases was 0·64%(634/99061).Moreover,of the 1616HCV-Ab positive patients,1278(79·08%)had HCV-RNA testing,and 951(74·41%)of them were HCV-RNA positive.It is noteworthy that only45·64%(434/951)of the HCV-RNA positive patients received standard Peg-interferon plus ribavirin(P/R)treatment and that 73·51%(272/370)of patients were cured.Additionally,10·96%(32/292)of the HCV-RNA positive patients were HBs Ag positive,and the cure rate for them was lower than that observed for HBs Ag-negative patients,but no significant difference was observed.Conclusions:1.The overall global prevalence of DAA RAVs was high irrespective of geography or genotype.However,the NI-based multi-DAA regimens had a low RAV prevalence,suggesting that these regimens are the most promising strategies for cure of the long-term HCV infection.2.This study reveals that HCV-Ab prevalence is low but is higher than the national average prevalence in China in 2006.The cure rate of P/R treatment was high,but the proportion of untreated patients was large.Thus,more efforts need to be made by the government to create policy for HCV treatment and prevention scientifically,so we can achieve the magnificent goal proposed by the WHO.