Study On Relationship Between HBV Genotype And Quasispecies And Antiviral Therapy Of Adefovir Dipivoxil

Part1 Research about HBV genotype switches after one year of adefovir dipivoxil treatmentObjective:To study whether the hepatitis B virus (HBV) genotypes of 52 chronic hepatitis B (CHB)patients, who have been treated with adefovir dipivoxil (ADV)for one year, have changed.Methods:52 patients with chronic hepatitis B were medicated with ADV for one year. Nested polymerase chain reaction (PCR) with multiple pairs of geno-type-specific primers was performed to investigate whether there were any differ-ences in the patients'HBV genotypes before and after the treatment, Subsequently.Results:Among the 52 CHB patients, one patient's HBV genotype changed from type B into a B/C mixed genotype after the ADV treatment.Conclusion:HBV genotype in CHB patients can change after ADV treatment.Part2 The relationship between HBV genotypes and efficacy of adefovir dipivoxilObjective:To investigate the effect of HBV genotypes on the antiviral efficacy of ADV in CHB patients.Methods:Firstly,52 patients with chronic hepatitis B were medicated with ADV for one year, then nested PCR with multiple pairs of genotype-specific primers was carried out to analyse the HBV genotyepe, At last, the antiviral efficacy at the 3rd,6th, 12th maonths after the ADV treatment were observed.Results:39 of the 52 patients were genotype B and 13 were genotype C. After 12 months'treatment, there were no significant differences in the ratio of HBV DNA negative conversion, alanine aminotransferase (ALT) normalization and HBeAg se-roconversion between patients with B genotype and C genotype HBV (P>0.05).Conclusions:HBV genotype has no significant effect on virological, biochemi-cal and immunological response to ADV.Part3 The relationship between adefovir dipivoxil and hepatitis B virus quasispecies mutationObjective:To study the quasispecies mutation of HBV P region and C region from CHB patients after one year of ADV treatment.Methods:37 CHB patients who had taken ADV orally for one year were se-lected as research objects, among whom 27 cases were completely virological re-sponse,5 were partial response,2 cases were non-response and 3 cases had virologi-cal breakthrough. All of them were HBV B genotype confirmed by nested PCR with multiple pairs of genotype-specific primers. First, HBV DNAs were extracted from all these 37 patients. Subsequently, PCR were adopted to amplify the P region and C region of HBV DNA. Lastly, melting curve were employed to analyse the quasispe-cies variance before and after ADV treatment.Results:Before the treatment of ADV, the virological response group had 4.59±0.57 peaks in HBV P region, while the partial and non-response group had 5.80±0.79 peaks, and the virological-breakthrough group had 6.67±0.58 peaks. Staticstics showed significant differences among each group(P<0.05).Among them, the virological response group had 5.50±0.84 peaks in HBV P region, the non-response group had 6.50±0.71 peaks in HBV P region.After one year of ADV treatment, the virological response group had 4.28±1.19 peaks in HBV P region, the partial response group had 5.00±0.71 peaks, while the non- response group had 5.00±0.00 peaks. Compared with that before treatment, there were no significant differences in HBV P region peaks of each group(P>0.05, respctively). Nevertheless, the virological-breakthrough group had 4.00±1.00 peaks in HBV P region peaks, apparently less than that before ADV treatment (P<0.05).Meanwhile, the count of HBV C region peaks in each group were not significant different pre- and post- ADV treatment (P>0.05).Conclusion:①The more quasispecies HBV P region has, the lower antiviral ef-ficacy ADV shows, and the the more likely to be resistant to ADV treatment; case of ADV resistance, the number of HBV P region quasispecies reduces signifi-cantly, however, perdominant quasispecies may appear at the same time;①The effct of ADV on the count of HBV C region quasispecies is not significant.