Analysis of hepatitis B virus genotype,virus loads,pre-core/core promoter region of nucleotide sequence in lamivudine-resistant hepatitis B virus in vivo

Objective To analyze the characteristics of lamivudine-resistant hepatitis B virus (HBV)genotypes B and C.Methods Serum samples were collected from 53 patients carrying lami- vudine-resistant HBV.HBV genotype was determined by the enzyme-linked immunosorbent assay (ELISA),HBV DNA was quantified by real-time fluorescent quantitave polymerase chain reaction (PCR)and the sequences of C gene and P gene were analyzed by sequencing and compared with stard- ard HBV genomic sequence in Genebank.Results In 53 lamivudine-resistant HBV infected patients, genotype B and genotype C accounted for 41.5%(22/53)and 58.5%(31/53),respectively.The occurrence of reverse transcriptase rt204Imutations(YIDD)was markedly higher in genotype C group than that in genotype B group(87.1% vs 36.4%,P0.01),whereas the occurrences of rt204V mutations(YVDD)and pre-core mutations were higher in genotype B group than those in genotype C group(63.6% vs 12.9%,77.3% vs 32.3%,respectively,both P value0.01).However,the viral loads in genotype C group were higher than in genotype B group((7.71±0.80)lg copy/mL vs(6.97±0.77)lg copy/mL,P0.01).No significant difference in the occurrence of core promoter muta- tions(T1762/A1764)was observed between both genotype group(genotype C:35.5%;genotype B: 31.8%,P0.05).The differences were not significant in the levels of HBV DNA between patients with YVDD and YIDD mutation.However,Serum HBV DNA levels in patients carrying HBV with mutations in both the precore region and the core promoter region were higher than those in patients carrying viruses without these mutations.Conclusions The YMDD mutational pattern in genotype B and genotype C is YVDD and YIDD respectively while the viral load of genotype B HBV is higher than that of genotype C viruses.Genotype B HBV is predisposed to develop precore mutation(G1896A).