The Effects Of Gene Variations In The Basic Core Promoter,the Pre C/C Region Of Hepatitis B Virus And The Genotype On The Antivirus Therapy Of α-IFN

Objectives: To investigate the effects of the genotype and the multiple mutations in the basic core promoter and the pre c/c region of HBV on the antivirus therapy ofα- Interferon.Methods: Thirty nine patients with chronic hepatitis B from a multicentre clinical research receivedα-interferon for six months were investigated. The HBV DNA of basic core promoter and the pre c/c region were sequenced by PCR combined direct sequencing from serum samples beforeα-interferon therapy, and the genotype was determined by restriction fragment length polymorphism, and to analyze the effects of the gene mutations and the genotype on the antivirus therapy ofα- Interferon.Results: 1 The thirty nine patients had no significant difference in age, gender,serum baseline ALT, baseline HBV DNA among the long-term response group, the relapse group and the no response group. 2 The double mutations of T1762/A1764 were found in eight of thirty nine patients (20.5%). The short-term response rate,the relapse rate and the long-term response rate had no significant differences between the groups with and without the double mutations of T1762/A1764 (P>0.05). 3 The A¹⁸⁹⁶ mutation was detected in eight patients (20.5%), and all of them were found with mutations in the lymphocyte epitopes of the core region. The double mutations of T1762/A1764 coexisted with the A¹⁸⁹⁶ mutation in only one case (2.6%). In the group with A¹⁸⁹⁶ mutation, the short-term response rate was similar with that in the wild type group (P>0.05), and the relapse rate toα- IFN was significantly higher and the long-term response rate was significantly lower than that in wild type group (P<0.05). At the end of follow-up, the negative rate of HBV DNA and the corresponding rate of HBeAg in those cases with A¹⁸⁹⁶ mutation were significantly lower than that in wild type group (P<0.05). 4 Core variations were different in the thirty nine patients. AA5, AA27, AA60, AA77, AA80, AA97, AA113 and AA135 were the hot spots of mutations. Mutations in the lymphocyte epitopes of the core region were found in thirty two patients(82%), and eight cases were the long-term responser, four cases were the relapser, twenty cases belonged to no-response group. The short-term response rate,the relapse rate and the long-term response rate had no significant differences between the groups with and without the mutations in the lymphocyte epitopes(P>0.05). There were eight patients of thirty nine, whose mutations of lymphocyte epitopes were greater than or equal to three. Among these eight cases, no one was long-term responser, two cases were the relapser, six cases belonged to no-response group. 5 The L60V mutation was found in fifteen patients (38.5%). At the end of follow-up, the long-term response rate toα- IFN ,the corresponding rate of HBeAg and the negative rate of HBV DNA in those cases with L60V mutation were significantly higher than that in wild type group(P<0.05). 6 The I97L mutation was found in fourteen patients (35.9%). At the end of the treatment and follow-up, the negative rate of HBV DNA in those cases with I97L mutation was significantly higher than that in wild type group (P<0.05). 7 The genotypes of serum HBVDNA in all patients were either type B or type C. There were twenty nine cases (74.4%) with type B and ten cases (25.6%) with type C. At the end of follow-up, the normalizing rate of ALT in the group of genotype B was significantly higher than that in the group of genotype C (P<0.05). 8 The rates of A¹⁸⁹⁶ mutation, 1762/1764 mutations, L60V mutation, I97L mutation and the mutation of the epitope 66-85 had no significant differences between the groups of genotype B and genotype C (P>0.05). In the group of genotype C, the rate of the epitope 77-82 mutation was significantly higher than that in the group of genotype B (P<0.05).Conclusions:1 1762/1764 mutations had no significant influence on the curative effect ofα- IFN. 2 A¹⁸⁹⁶ mutation had no significant influence on the short-term curative effect ofα- IFN, but it was an important factor to relapse. 3 The mutation of L60V and I97L may be benefit to the curative effect ofα- IFN. 4 The more mutations happened in the lymphocyte epitopes of Core region, the worse curative effectsα- IFN made. 5 The curative effect ofα- IFN had no significant difference between the groups with genotype B and genotype C.