The Relevance Of Polymorphisms Of Type I Interferon Receptor 1 Promoter And The Initial Response To Interferon Alpha In HBeAg-positive Chronic Hepatitis Patients

Background The hepatitis B is a range of infectious diseases , partly mey develop to cirrhosis and liver cancer. Antiviral therapy is the cure way to treat the chronic hepatitis B. Antiviral therapy can block or delay the progression to cirrhosis and liver cancer, improve the prognosis, and increase survival of the patients . Currently, IFN-αtreatment remains a mainstay treatment in active hepatitis B. Only 30%-40% of the treated patients show response to IFN-α. The antiviral efficacy of interferon is influenced by the virus and the host factors. The host genetics is one of the important factors of the IFN response , which also is the subject of research studies. This study aimed at investigating the relation between polymorphisms of type I interferon receptor 1 promoter and the initial response to IFN-αtherapy.Methods In our prospective study ,Polymorphisms of IFNAR1 were examined by polymerase chain reaction in 105 patients with HBeAg-positive CHB. Purified PCR products were characterized by DNA sequencing,and ALT, HBV DNA level and HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were determined before and after the therapy (12 weeks). Find out indexes for predicting the effect of the initial response to IFN-αtreatment. Results Among the 105 patients, 14(13.3%)had initial virologic response to IFN-αtherapy, 37(35.2%)had Serological response, 12(11.4%)had Seroconversion. The efficacy of IFN-αtherapy had significant difference in different ages (P<0.05). The baseline ALT level between 3 ULN and 10 ULN had more effective (P<0.05), and the baseline HBV-DNA level was lower than 107copies/ml had more effective (P<0.05). Four polymorphic sites were identified at loci-568,-408,-3,and-77, and they were separately: -568G/C, -408C/T, -3C/T and-77 GT microsatellite repeatsequence (-77(GT)n). No significant difference among the genotypes of the four sites (-568G/C, -408C/T, -3C/T and -77(GT)n) was found in terms of the distribution of gender, age, initial ALT level, pretreatment HBV DNA, and type of IFN-α. Alleles or genotype frequencies at these sites (loci -568, -408, -77, and -3) were not different between responders and nonresponders in terms of initial virological response, seroconversion (P>0.05).Conclusion Genetic polymorphisms of type I interferon receptor 1 have no relation with the initial virological response to IFN-αtherapy in Chinese Han patients with CHB. The efficacy of IFN-αis close relation to the levels of ALT, HBV DNA and age.