B和C基因型乙型肝炎病毒对阿德福韦酯治疗的病毒学应答比较

Comparison of antiviral responses to adefovir dipivoxil therapy of genotype B and genotype C HBV infected patients

目的阐明不同基因型HBV对阿德福韦酯治疗反应是否存在差异。方法首先利用型特异引物PCR法结合型特异核苷酸分析法检测HBV基因型，然后根据基因型对阿德福韦酯Ⅲ期临床资料进行分析及统计学处理（计量资料用t检验，计数资料用卡方检验）。结果177例临床标本检出B基因型HBV感染者102例，C基因型感染者65例，B＋C混合型感染者6例，B＋D混合型感染者4例。治疗第12、24周时，B基因型组和C基因型组血清HBVDNA下降均值分别为2.2log10拷贝／ml、2.1log10拷贝／ml和2.7log10拷贝／ml、2．4log10拷贝／ml，两组差异均无统计学意义（P〉0．05），第48周时两组HBVDNA分别下降3.6log10拷贝／ml和3．1log10拷贝／ml，差异有统计学意义（P〈0．05）。治疗结束时（48周）B基因型组和C基因型组分别有43例（42．2％）和22例（33．8％）出现血清HBVDNA转阴，差异有统计学意义（P〈0．05）；两组患者HBeAg阴转率和抗-HBe血清转换率分别为30．4％、29．2％和21．6％、20．0％，差异无统计学意义（P〉0．05）。两组患者血清ALT复常率在治疗第12、24、36周和48周时分别为35．3％、33．9％，51．0％、53．9％，63．4％、61．5％和83．3％、81．5％，各时间段两组ALT复常率差异均无统计学意义（P〉0．05）。结论阿德福韦酯治疗慢性乙型肝炎48周时，部分病毒学指标（如血清HBVDNA下降均值和HBVDNA阴转率）B基因型优于C基因型HBV感染者。但由于阿德福韦酯起效较慢，抑制病毒作用相对较弱，有必要延长治疗时间进一步证实这一现象。

Objective To investigate the role of HBV genotypes on their response to adefovir dipivoxil （ADV） antiviral therapy. Methods HBV genotypes from 177 HBeAg-positive chronic hepatitis B （CHB） patients were identified and the patients were treated with ADV 10 mg per day for 48 weeks. The clinical data in terms of serum HBV DNA seroclearance, mean HBV DNA reduction （log value）, HBeAg loss, anti-HBe seroconversion and serum ALT of those patients were analyzed against their HBV genotypes. Results Genotype B and genotype C were found in 102 and 65 cases, respectively. The mean HBV DNA reduction in patients with genotype B and genotype C at their treatment times of 12, 24 and 48 weeks was 2.2 logj0copies/ml, 2.1 logl0copies/ml （P 〉 0.05）, 2.7 logl0copies/ml, 2.4 logl0copies/ml （P 〉 0.05） and 3.6 log10,copies/ml, 3.l log10copies/ml （P 〈 0.05）, respectively. At the end of the therapy （48 weeks）, 43 （42.2%） patients with genotype B HBV infection and 22 （33.8%） oatients with genotype C HBV infection had achieved HBV DNA seroclearance （P 〈 0.05）. Conclusions Our results suggest that genotype B HBV has a better virological response to ADV therapy in HBeAg-positive chronic hepatitis B patients than that of genotype C. Longer terms of ADV treatment are needed to confirm this conclusion.