拉米夫定联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎患者的疗效及其与HBV基因型的相关性

Therapeutic Efficacy of Lamivudine Combined with Adefovir Dipivoxil in the Treatment of Lamivudine-resistant Chronic Hepatitis B Patients and Its Relationship with HBV Genotype

目的:评价拉米夫定(LAM)联合阿德福韦酯(ADV)治疗LAM耐药慢性乙型肝炎(以下简称"乙肝")患者的疗效,并研究疗效与乙型肝炎病毒(HBV)基因型的相关性。方法:选择2012年12月-2014年12月LAM耐药慢性乙肝患者101例,均给予LAM+ADV联合治疗至少24个月,并行定期门诊或电话随访。采用聚合酶链反应-反向点杂交法检测各患者的HBV基因型,采用χ~2检验、Kaplan-Meier法、Log-rank检验比较随访第6、12、18、24个月时各基因型患者的病毒学应答(HBV-DNA清除率)和生化学应答[丙氨酸转氨酶(ALT)复常率、乙型肝炎e抗原(HBeAg)血清转化率]情况。结果:无失访病例,随访率为100%。共检出HBV基因型2种,其中B型患者34例(33.7%)、C型患者67例(66.3%)。101例患者在上述各时间点的HBV-DNA清除率分别为34.7%、55.4%、79.2%、93.1%;随访第6个月时,B型患者的HBV-DNA清除率和累积HBV-DNA清除率均显著高于C型患者,差异均有统计学意义(P<0.05),而其他时间点各基因型患者HBV-DNA清除率、累积HBV-DNA清除率比较,差异均无统计学意义(P>0.05)。101例患者在上述各时间点的ALT复常率分别为40.6%、69.3%、82.2%、84.2%;各时间点各基因型患者ALT复常率、累积ALT复常率比较,差异均无统计学意义(P>0.05)。101例患者在上述各时间点的HBeAg血清转化率分别为10.9%、19.8%、24.8%、29.7%;各时间点各基因型患者HBeAg血清转化率、累积HBeAg血清转换率比较,差异均无统计学意义(P>0.05)。结论:LAM联合ADV对LAM耐药慢性乙肝患者有效,且HBV基因B型患者的病毒学应答要早于C型患者。

OBJECTIVE： To evaluate therapeutic efficacy of lamivudine （LAM） combined with adefovir dipivoxil （ADV） in the treatment of LAM-resistant chronic hepatitis B patients, and to study the relationship of therapeutic efficacy with hepatitis B virus （HBV） genotype. METHODS： A total of 101 LAM-resistant chronic hepatitis B patients selected during Dec. 2012 to Dec. 2014 were given LAM＋ADV for 24 months at least. Regular outpatient visits or telephone follow-up were also performed. Polymerase chain reaction-reverse dot blot method was used to determine the HBV genotype. Chi-square test, Kaplan-Meier meth- od and Log-rank test were used to compare the virological response （HBV-DNA clearance rate） and biological response （ALT normalization rate and HBeAg seroconversion rate） among different genotypes at the 6th, 12th, 18th and 24th month of fol- low-up. RESULTS： The follow-up rate was 100%, without missed follow-up. Two genotypes were detected, including 34 pa- tients （33.7%） with genotype B and 67 patients （66.3%） with genotype C. At each time point mentioned above, the HBV-DNA clearance rates of 101 patients were 34.7%, 55.4%, 79.2% and 93.1%. At 6th month, HBV-DNA clearance rate and accumula- tive HBV-DNA clearance rate of genotype B were significantly higher than genotype C, with statistical significance （P〈0.05）. There was no statistical significance in HBV-DNA clearance rates or accumulative HBV-DNA clearance rates between different genotypes at other time points （P〉0.05）. At each time point mentioned above, ALT normalization rates of 101 patients were 40.6%, 69.3%, 82.2%, 84.2% ; there was no statistical significance in ALT normalization rates or accumulative ALT normaliza- tion rates between different genotypes （P〉0.05）. At each time point mentioned above, the HBeAg seroconversion rates of 101 patients were 10.9%, 19.8%, 24.8%, 29.7% ; there was no statistical significance in the HBeAg seroconversion rates or accu- mulative HBeAg seroconversion rates between different genotypes （P〉0.05）. CONCLUSIONS： LAM combined with ADV is ef- fective for LAM-resistant chronic hepatitis B patients. Moreover, the combination therapy can achieve earlier viological response in patients with genotype B than those with genotype C.