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目的从血清肿瘤坏死因子α(TNF-α)水平及其-238、-308位点基因多态性和HBV基因型、亚型等因素探讨阿德福韦酯(ADV,商品名:名正)治疗HBeAg阳性慢性乙型肝炎(CHB)联合应答的预测因素。方法对203例HBeAg阳性CHB患者采用ADV10mg/d治疗48周,并应用PCR-RFLP检测TNF-α-238及-308位点基因多态性,ELISA测定基线血清TNF-α水平,HBV基因分型荧光定量PCR法检测HBV基因型或HBVS基因直接测序法检测HBV基因型、亚型,Logistic回归分析影响ADV应答的因素。结果 203例患者24周和48周HBVDNA转阴率、ALT复常率、HBeAg转阴率及转换率、应答率分别为31.5%、59.1%、15.8%、8.9%、13.3%和58.6%、78.3%、29.6%、16.7%、25.6%。获得24周应答的患者较无应答者的基线ALT、TNF-α水平高,而基线HBVDNA载量低(P<0.05);获得48周应答的患者较无应答者的24周HBeAg转阴率及转换率、基线TNF-α水平高,而基线HBVDNA载量低(P<0.05)。结论 HBeAg阳性CHB患者ADV治疗24周应答的预测因素是基线ALT、TNF-α、HBVDNA;48周应答的预测因素是24周HBeAg转阴率及转换率、基线HBVDNA及TNF-α。
Objective To investigate the effects of adefovir dipivoxil (ADV) on the level of tumor necrosis factor-α (TNF-α), the gene polymorphisms at -238 and -308 and HBV genotypes and subtypes, Predictors of combined response to treatment of HBeAg-positive chronic hepatitis B (CHB). Methods Twenty-three patients with HBeAg-positive CHB were treated with ADV10 mg / d for 48 weeks. The gene polymorphisms of TNF-α-238 and -308 were detected by PCR-RFLP. The levels of TNF-α, HBV genotype Fluorescent quantitative PCR was used to detect HBV genotype or HBV S gene direct sequencing to detect HBV genotypes and subtypes. Logistic regression analysis was used to analyze the factors influencing ADV response. Results The negative rate of HBVDNA, ALT normalization rate, HBeAg negative conversion rate and response rate in 203 patients at 24 weeks and 48 weeks were 31.5%, 59.1%, 15.8%, 8.9%, 13.3% and 58.6%, respectively %, 29.6%, 16.7%, 25.6%. Patients with 24-week response had higher baseline ALT and TNF-α levels than those without responders and low baseline HBV DNA load (P <0.05). Patients with 48-week response had significantly lower HBeAg negative rates at 24 weeks Conversion rate, baseline TNF-α levels were high, while baseline HBVDNA loading was low (P <0.05). Conclusions The predictors of 24-week response to ADV in patients with HBeAg-positive CHB are baseline ALT, TNF-α, and HBVDNA. The predictors of 48-week response are HBeAg negative rates and conversion rates at 24 weeks, baseline HBVDNA, and TNF-α.