阿德福韦酯治疗慢性乙型肝炎疗效观察及病毒P基因区变异分析

目的探讨阿德福韦酯（ADV）治疗慢性乙型肝炎患者的疗效及耐药变异情况。方法89例慢性乙型肝炎患者中，66例为拉米夫定（LAM）耐药变异患者（联合治疗组），接受阿德福韦酯联合拉米夫定治疗；23例为初治患者（ADV组），接受阿德福韦酯单药治疗，两组患者基线特征无差异。检测分析患者血清HBVDNA、ALT、HBeAg的变化，以及用药48～144周时乙肝病毒P基因区变异发生情况。结果用药12周、24周、48周时，HBVDNA阴转率联合用药组分别为39．4％、54．5％、75．8％，ADV组分别为0％、13．0％、47．8％，联合用药组的病毒学应答高于ADV组（P〈0．05）；12周、24周时ALT复常率联合用药组与ADV组各为40．9％、59．1％与0％、21．7％，联合用药组的生物化学应答高于ADV组（P〈0．05）；48周时联合用药组与ADV组的ALT复常率、HBeAg阴转率差异无统计学意义（P〉0．05）。89例患者用药48周、96周、144周病毒变异发生率分别为0％、3．4％、5．6％；B基因型与c基因型患者病毒变异发生率各为8．6％与10．5％，变异率差异无统计学意义（P〉0．05）；联合用药组与ADV组病毒变异发生率分别为9．1％与8．7％，变异率差异无统计学意义（P〉0．05）。结论阿德福韦酯是治疗慢性乙型肝炎的有效抗病毒药物，且耐药变异率较低，其对拉米夫定耐药变异株的抑制作用强于HBV野毒株；阿德福韦酯联合拉米夫定治疗拉米夫定耐药，能提高抗病毒疗效、不增加耐药突变发生率。

Clinical Effect of Adefovir Dipivoxil in Treating Chronic Hepatitis B and the P Gene of Hepatitis B Virus Mutation Analysis

Objective To explore the effects of adefovir dipivoxil （ADV） in treating chronic hepatitis B, and virus drug-resistant mutation. Methods Among 89 patients with chronic hepatitis B ,66 cases were lamivudine-resistant mutation patients （group A ）, receiving adefovir dipivoxil combined with lamivudine（LAM） therapy, and 23 cases were newly diagnosed patients （ group B ） , receiving adefovir monotherapy. There were no differences in the baseline characteristics between group A and B. Patients were analyzed with HBV DNA, ALT, HBeAg, and the mutations in the P gene of hepatitis B virus（HBV） were detected medication for weeks 48 - 144. Results At week 12,24 and 48,Serum HBV DNA negative rate was 39.4% ,54.5% and 75.8% in group A,0% , 13.0% and 47.8% in group B. Virological response was higher in the group A than group B （P 〈 0.05）. At week 12 and 24,ALT normalization rate was 40.9% and 59.1% in group A,0% and 21.7 % in group B. Biochemical response was higher in the group A than group B （P 〈 0.05 ）. At 48 week, no significant difference was found in Serum HBeAg negative rate and ALT normalization rate between group A and B （ P 〉 0.05 ）. Medication for 48,96 and 144 weeks,the virus mutation rates was 0% ,3.4% and 5.6%. In genotype B and C, the virus mutation rates were 8.6% vsl0.5 %, which had no statistic difference （P 〉 0.05 ）. In group A and B, the virus mutation rates were 9.1% vs 8.7% ,which had no statistic difference （P 〉 0.05 ）. Conclusion Adefovir dipivoxil is efficacious for chronic hepatitis B, and lower rate of drug-resistant mutation, and the inhibitory effect for lamivudine-resistant mutants is stronger than HBV wild strain. ADV combined with LAM therapy lamivudine resistance can improve the antiviral efficacy, and reduce the incidence of drug-resistance mutations.