| Background Antiviral therapy is the key to the treatment of patients with chronic hepatitis B virus(HBV)infection.Currently,the main anti-HBV drugs include interferon and the nucleoside analogues(NAs).With the advantages of oral administration,relatively lower price,and good antiviral effect,NAs are now widely used in the anti-HBV therapy.However,NAs inhibit the replication of HBV rather than completely clear it.Thus,Long-term administration of nucleoside(acid)analogs can lead to drug resistance which causes the relapse of the disease or even worse.Objective The study aims to analyze the drug-resistant related mutation loci in HBV reverse transcriptase region,the combination mode of the mutation loci,the levels of HBV DNA in chronic HBV infected patients treated with NAs.It is hopeful to provide reference for the anti-HBV therapy of NAs.Methods One hundred and forty-one patients with chronic HBV infection were selected in the study,of which the 107 cases with NAs treatment were set as the treatment group,and the rest 34 patients receiving no antiviral treatment were set as the control group.Drug-resistant related mutation loci in HBV reverse transcriptase region was determined by the reverse linear probe hybridization PCR(PCR-RLP).The level of HBV DNA was detected by real-time fluorescence quantitative PCR.And immune markers of HBV were examined by Enzyme-linked immunosorbent assay(ELISA).Finally,the characteristics of drug resistance-related mutations and the clinical data of the study cases were analyzed statistically.Results The detection rate of drug-resistant related mutation loci in the poor effective treatment group(82.5%)was significantly higher than that in the untreated control group(5.9%)and the effective group(0%)(P<0.01).There were 97 cases who received NAs showing poor antiviral effect in the treatment group,of which 80 ones possessed 140 drug-resistant mutation loci.The major mutation sites included 45 rtM204 I,32 rtM204 V,10 rtN236 T,25 rtL180 M and 28 rtA181 V.Main combination modes of the mutation loci were rtL180 M + rtM204 I,rtM204V,rtM204 I + rtM204 V,rtA181V + rtM204 V,rtM204I and rtA181 V + rtN236 T,etc..Mutation detection rate in the 51 cases with poor NAs response was 70.59%,with 95.65% in the 46 virological breakthrough cases(P<0.01).Mutation in those who received monotherapy was usually detected much earlier than that in multi-drug treated ones(P<0.01).The longer the treatment time of NAs,the higher the detection rate of drug-resistance mutation sites(P <0.01).The higher the level of HBV-DNA,the higher the detection rate of drug-resistance(P <0.01).Conclusions 1.NAs treatment of chronic hepatitis B can lead to mutations in HBV reverse transcriptase region,and NAs anti-hepatitis B virus ineffective is closely related to mutations in HBV reverse transcriptase region.2.Different NAs drugs lead to different characteristics of mutation loci and combination modes of the mutation loci in HBV reverse transcriptase region of chronic hepatitis B patients.3.Selection of NAs,treatment time,level of HBV-DNA in patients may all have an important impact to drug-resistance related mutations in HBV reverse transcriptase region.It is suggested that NAs drug resistance-related mutations and level of HBV-DNA in patients should be detected before treatment or be monitored during treatment,which can provide important reference for clinical antiviral therapy of chronic hepatitis B. |
