ABSTRACT
<p><b>OBJECTIVE</b>To determine the prevalence of mutations in the non-structural protein 5B (NS5B) of the hepatitis C virus (HCV),which are associated with natural resistance to non-nucleoside and nucleoside polymerase inhibitors (PIs),in treatment-naive hepatitis C patients in south China.</p><p><b>METHODS</b>A nested PCR protocol that amplified three different regions of NS5B was used to detect the naturally occurring drag-resistant substitutions.Direct PCR sequencing was performed to analyze the sequences.</p><p><b>RESULTS</b>NS5B mutations known to confer resistance to nucleoside PIs,such as A15G,S96T and S282T,were mainly detected in HCV genotype 6a (20/88,22.73%).Of the NS5B mutations known to confer resistance to non-nucleoside PIs,C316N and S365A were detected in HCV genotype lb (60/60,100% and 2/60,3.33%, respectively) and I482L and V499A were mainly detected in HCV genotype 2a (9/9,100% and 4/4,100%, respectively) and HCV genotype 6a (9/9,100% and 4/4,100%, respectively).Other NS5B mutations found in the study population included A1 5S,S365F,S365P,S368A and S368L;although none of these has been previously shown to confer resistance to PIs.</p><p><b>CONCLUSION</b>Naturally occurring dominant PI resistance mutations in NS5B exist in treatment-na(i)ve hepatitis C patients in south China and may be related to the virus genotype.</p>
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Humans , Antiviral Agents , Pharmacology , China , Drug Resistance, Viral , Genotype , Hepacivirus , Genetics , Hepatitis C , Drug Therapy , Virology , Mutation , Viral Nonstructural Proteins , GeneticsABSTRACT
Objective To investigate the genotype distribution of hepatitis C virus (HCV) in Guangdong Province by linear probe assay (LiPA) and core,non-structural protein 5B (NS5B) sequence analysis,and to evaluate the accuracy of LiPA for genotyping.MethodsOne hundred and ten HCV specimens from chronic hepatitis C (CHC) patients in Guangdong Province were genotyped by both core,NS5B sequence analysis and INNO-LiPA 2.0.The data were then analyzed with SPSS 10.0 software.ResultsAmong the 110 specimens,core and NS5B fragment could be amplified from 97 and 62 specimens,respectively,while both fragments were obtained from 57 specimens. The results of genotyping by core sequence analysis were completely consistent with the results of NS5B sequencing.One hundred and two specimens were classified into five subtypes,i.e.genotype 1a,2a,3a,3b,6a,with frequencies of 61.8％ (64),9.8％ (10),3.9％ (4),3.9％ (4),20.6％ (21),respectively.All but genotype 6 strains can be genotyped correctly by using INNO-LiPA 2.0.However,only subtype 1b and 3b could be genotyped accurately.81.5％ genotype 6a strains were genotyped as 1b by mistake. Conclusions Genotype 6a has become the second most prevalent genotype in Guangdong Province.The LiPA cannot distinguish genotype 6a from 1b strains accurately which needs further investigation.
ABSTRACT
Objective To investigate the efficacy of pegylated interferon (PEG-IFN)+ ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC),and to evaluate the predictors of treatment response.Methods One hundred and thirty CHC patients treated with PEG-IFN a-2a 180 μg weekly or PegIFNα-2b 80 μg weekly plus RBV 900-1200 mg/d for 48 weeks in Guangdong Province were enrolled.The clinical data including age,gender,body mass index (BMI),spleen index (SPI),the diameter of portal vein (PV),hepatitis C virus (HCV) genotype,HCV RNA level were collected at baseline,week 4,12,24,48 of treatment and week 24 of follow-up.Patients obtained sustained virological response (SVR) were compared to those with non-sustained virological response (NSVR).The related factors of SVR were analyzed.The data were compared by t test,chi square test or Logistic regression.Results The total SVR rate was 84％ (109/130),among which rapid virological response ( RVR ),early virological response ( EVR ),and end-of-treatment virological response (ETVR) were 21％ (27/130),72％ (94/130) and 93％ (121/130),respectively.HCV genotype was determined in 70 patients and the SVR rate was 82 ％ (45/55) in the genotype 1 patients and 87％ (13/15) in the genotype non-1 patients.Age,baseline HCV RNA,BMI and SPI were all negatively associated with SVR rate (regression coefficient＜0,all OR＜1,all P＜0.05),while EVR and total cumulative treatment dose of RBV were positively associated with SVR rate (regression coefficient＞0,both OR＞ 1,both P＜0.05).However,RVR,PV and total cumulative treatment doses of PEG-IFN were not associated with SVR rate (P＞0.05).Conclusions The SVR rate of PEG-IFN plus RBV combined treatment is high in CHC patients and more than 80％ of patients can be cured.However,the SVR rates are lower in patients elder than 35 years,with previous treatment failure history,baseline HCV RNA＞6 × 105 IU/mL,BMI＞26 kg/m2,SPI＞40 cm2,or the total cumulative treatment doses of RBV less than 80 ％ of standard dose.