HBVB／C混合基因型对慢性乙型肝炎干扰素α抗病毒疗效的影响

The influence of B/C mixed HBV genotype on the interferon-α therapy for patients with chronic hepatitis B

目的探讨慢性乙型肝炎（CHB）患者B／C混合基因型乙型肝炎病毒（HBV）感染与干扰素α（IFN—α）治疗效果的相关性。方法经IFN—α治疗的HBeAg阳性B／C混合基因型CHB患者，采集治疗基线及治疗12周后血清，扩增HBV全基因组并进行克隆，每份标本17—20个克隆测序并进行序列分析及分子进化分析。结果2例HBeAg阳性B／C混合基因型感染CHB患者，优势病毒株均为C型毒株。经IFN-α治疗后，1例发生完全病毒学应答，1例发生部分病毒学应答并且治疗后B基因型病毒株完全清除。完全应答者与部分应答者治疗前C基因型准种复杂度为0．5562VS0．6305，部分病毒学应答者治疗后全基因组准种复杂度高于治疗前C基因型准种复杂度（0．6305VS0．7200），全基因组核苷酸水平的平均遗传距离高于治疗前（0．00454VS0．00648核苷酸替换／位点）。结论（1）B／C混合基因型感染CHB患者优势病毒株为C型毒株。（2）B基因型病毒株对干扰素的敏感性高于C基因型，B／C混合基因型感染患者治疗后病毒准种复杂度及准种多样性升高。

Objective To study the correlation of B/C mixed HBV genotype and the interferon-or therapy for patients with chronic hepatitis B. Methods Two chronic hepatitis B patients infected with B/C mixed genotype HBV who underwent IFN-α therapy were examined. The complete genome of HBV was amplified by PCR from the serum at baseline and treatment week 12, then cloned and sequenced. Sequence analysis and molecular evolution analysis were undertaken to all the sequences. Results The virus strains with genotype C were dominant in both two subjects. One of them had complete virological response, the other had partial virological response after 12 weeks of IFN-α therapy, the genotype changed to C in the latter case. The quasispeeies complexity of genotype C in patients had complete virological response and partial virological response was 0. 6305 versus 0. 5562. The quasispecies complexity of genotype C in patient had partial virological response was higher after therapy （0. 6305 versus 0. 7200） , and the mean genetic distance was also higher after therapy （0. 00454 versus O. 00648 substitutions/site）. Conclusions （ 1 ） The virus strains with genotype C were dominant in chronic hepatitis B patients with B/C mixed HBV genotype infection. （2） In chronic hepatitis B patients infected with B/C mixed genotype HBV, virus strains with genotype B were more sensitive than genotype C. The genetic heterogenity was higher after therapy in patients had partial virological response.