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目的 :探讨乙型肝炎病毒基因不同位点变异及基因型对干扰素疗效的影响。方法 :研究 17例HBeAg阳性慢性乙型肝炎病人的临床表现、生化、血清学和病毒学指标 ,并分析这些病人干扰素治疗 (IFN -α2b 3MU ,每周三次 ,疗程 6个月 )前血清标本中的病毒X基因和前c c基因的DNA序列。结果 :所有发生T1 76 2 -A1 76 4突变的 5例病人对干扰素治疗均有应答 ,而其余 12例病人中仅 2例有应答。在 5例既有前c区A1 896 变异又有c区抗原决定簇aa 10 7- 118变异的病人中 ,4例无应答 ,1例有应答。其他 3例有A1 896 位点变异的病人中 ,2例同时伴有 1～ 2处淋巴细胞表位变异的病人有应答 ,而 1例伴有 5处淋巴细胞表位变异的病人无应答。应答者的血清HBVDNA复制水平低而抗HBc -IgM滴度高。所有病人的血清HBVDNA基因型均为B型或C型。结论 :提示HBV基因变异、血清病毒载量和抗HBc -IgM滴度等可能是干扰素治疗效果的预测指标 ,但有待临床和实验室研究的进一步验证。
Objective: To investigate the effect of different genotypes and genotypes of hepatitis B virus on the curative effect of interferon. Methods: The clinical manifestations, biochemical, serological and virological indices of 17 patients with HBeAg-positive chronic hepatitis B were studied. Serum samples of these patients before interferon treatment (IFN-α2b 3MU, three times a week, for 6 months) In the virus X gene and the former cc gene DNA sequence. Results: All 5 patients who developed the T1 76 2 -A1 76 4 mutation responded to interferon treatment, whereas only 2 of the remaining 12 patients responded. Of 5 patients with both pre-c A1 896 mutation and c-region antigenic determinant aa 10 7- 118 mutation, 4 had no response and 1 had a response. Of the other 3 patients with Al 896 locus mutations, 2 responded to 1 to 2 lymphocyte epitope variants simultaneously, whereas 1 patient with 5 lymphocyte epitopes did not respond. Responders had low serum HBVDNA replication and high anti-HBc-IgG titers. Serum HBVDNA genotypes were all B or C in all patients. Conclusion: It is suggested that HBV gene mutation, serum viral load and anti-HBc-IgM titer may be predictors of interferon treatment efficacy, but further validation is needed in clinical and laboratory studies.