Sequence Variations of the Hypervariable Region of HCV and Their Clinical Significance / 复旦学报（医学版）

ABSTRACT

Purpose　To understand the clinical significance of sequence variations in the hypervariable region(HVR) of hepatitis C virus during infections.　Methods　8 cases of acute hepatitis C and 20 of chronic hepatitis C were followed for two years.Blood samples were taken at intervals of six months for analysis of HCV?HVR sequences by reverse transcription-polymerase chain reaction(RT?PCR) and direct sequencing methods.　Results　Results showed that HCV?HVR sequences of the 28 patients changed in various degrees.92% of these nucleotide substitutions led to changes of corresponding amino-acid sequences.Only 8% of changed nucleotide were synonymous substitutions.Variation of amino acid ranged from 1 to 20(mean 8,30%).The most common nucleotide substitution(62%) occurred in the first position of codon,31% in the second and the rest in the third.HVR variation rate was 0.89×10-1 per genome site per year in acute hepatitis C,compared with 2.31×10-1 per genome site per year in chronic hepatitis C (P<0.05),but variations had no relation to HCV subtype.Variation of HVR in the flare up type (ALT>150 u/L) was much more than that in the quiescent type (ALT<100 u/L).　Conclusions　Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host immune pressure and might play a major role in the establishment of persistent infection as well as in the flare-up of hepatitis.