阿德福韦酯抗病毒疗效与乙型肝炎病毒基因型的关系

Relationship between antiviral efficacy of adefovir dipivoxil and HBV genotypes

目的探讨乙型肝炎病毒（HBV）不同基因型对阿德福韦酯（ADV）抗病毒疗效的影响。方法对16例应用ADV治疗的慢性乙型肝炎（CHB）患者，采用荧光定量PCR法检测其HBVDNA的水平，全自动生化仪检测其丙氨酸氨基转移酶（ALT）的水平。用PCR法扩增用药前（基线）、用药后28、52和92周时的HBV全基因组，克隆后进行全基因组序列测定及基因型分型。观察治疗12、16、28、40、48、52、68、80及92周时抗病毒疗效。结果（1）不同基因型CHB患者治疗前HBVDNA及AI．T水平差异无统计学意义（均P〉0．05）。HBV基因型B型、C型CHB患者治疗12、16、28、40、48、52、68、80和92周时HBVDNA载量的变化、ALT复常及HBeAg血清转换等指标差异均无统计学意义（均P〉0．05）。HBV基因型B型、C型患者治疗92周HBV DNA有效抑制率均为100％。（2）16例CHB患者的HBV基因型分布为B型9例，C型6例，B和C混合型1例。5例患者在接受ADV治疗后基因型由B型变为C型或从C型变为B型。结论HBV基因型为B型或C型的CHB患者对ADV治疗的病毒学、血清学和生物化学应答无显著差异，提示HBV基因型可能对ADV的疗效无影响。

Objective To study the relationship between Hepatitis B virus （HBV） genotypes and autiviral efficacy of adefovir dipivoxil （ADV）. Methods Sixteen patients with chronic hepatitis B （CHB） received ADV therapy for 92 weeks. Blood samples were collected at week 0, 12, 16, 28, 40,48, 52, 68, 80 and 92. Alanine aminotransferase （ALT） and HBV DNA titer were determined by automatic biochemistry analysator and fluorescence quantitative real-time PCR respectively. HBV genomes were retrieved with full- length PCR from sera samples of week 0, 28, 52 and 92. And then the genomes were sequenced and genotyped. The curative effects were compared in different genotypes at all time points. Results （1） There were no statistically significant differences in levels of HBV DNA and ALT of different genotype patients with CHB before ADV treatment （all P〉0.05） . There were no statistically significant differences in changes of HBV DNA load , normalization of ALT and seroconversion of HBeAg at all time points between the HBV genotype B and HBV genotype C patients with CHB （all P〉0.05 ）. The effective inhibition rates of HBV DNA were both 100% in the HBV genotype B and HBV genotype C patients at week 92. （2） In all the 16 patients with CHB, 9 patients were genotype B, 6 patients were genotype C and 1 patient was co-infected by genotype B and C. HBV genotype switching was observed in 5 patients （from B to C, or from C to B） after ADV treatment. Conclusions There is no significant difference in response to ADV treatment between the HBV genotype B and HBV genotype C patients with CHB in terms of virology, serology and biochemistry. It indicates that the HBV genotypes may have no influence on the antivira｜ efficacy of ADV treatment.