Analysis Of Full-length Hepatitis B Virus Genomes Mutation Isolated From HBeAg Positive Chronic Hepatitis B Patients And Its Relationship With Interferon-α Therapy

Object:To study the genetic mutation of full-length Hepatitis B Virus (HBV) genomes isolated from the patients with chronic hepatitis B before treated with interferon and its relationship with the efficacy of interferon-α.Methods: Amplified the full-length HBV genomes by PCR from the serum chronic hepatitis B patients before treated with interferon, sequencing and analysis of genetic variation and its response to interferon-a therapy.Results:Obtained thirty-three full-length HBV DNAs from the chronic hepatitis B patients before treated with interferon, which could be categorized into genotype B or C. It conclused that compared to standard strains, HBV deletion mutation rates in the B, C genotype were 14.3%(2/14) and 63.2%(12/19), respectly, HBV pre-S2 nt19-nt56 deletion mutation occurs only in genotype C patients who had response by interferon treatment, the response rate was 15.2%(5/33), accounted for 50% of effective cases in C genotype (5/10).TP+ space area is 6 deletion full-length HBV DNAs(?), five cases of interferon therapy nonresponse, one case of response. Only one HBV insertion full-length HBV DNAs, 3460bp, B genotype is interferon therapy nonresponse. HBV mutations results:four cases of C genotype with ntG2699T variation in the interferon response patients, accounted for 40% of genotype C response cases, and occurred in the absence of pre-S2 deletion cases. Therefore, pre-S2 deletion mutation and ntG2699T variations accounted for 90% of genotype C response cases, can be used as the factors that predict response to interferon. In addition, in vitro with anti-interferon effect of T1504C, A1762T, G1764A, G1896A mutation had no effect on the efficacy of interferon in our study. TP257 found, the H135Y and Q176H of B genotype; the N89D and K142Q/K142E of C genotype may have anti-interferon effect. Conclution:The prevalence of HBV deletion mutation between B andC genotype is significant differences; HBV pre-S2 deletion mutant and ntG2699T variation associated with the C genotype and response to interferon; the H135Y and Q176H of B genotype and the N89D and K142Q/K142E of C genotype may have anti-interferon effect.