期刊存档
阿德福韦酯治疗HBeAg阳性慢性乙型肝炎联合应答的预测因素分析
高海兵，潘晨，林明华，周锐，郑玲，林太杰，许利军，原津津，方建凯高海兵、潘晨、林明华、周锐、郑玲、林太杰、许利军、原津津、方建凯，福建医科大学附属传染病医院 福州市传染病医院肝病科，350025
基金项目： 福州市社会发展科技项目(2008-s-74)
摘 要: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ADV 10 mg/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HBV S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HBV DNA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HBV DNA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HBV DNA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、HBV DNA；48周应答的预测因素是24周HBeAg转阴率及转换率、基线HBV DNA及TNF-α。
关键词:肝炎，乙型，慢性； 肿瘤坏死因子α； 基因型； 阿德福韦酯； 联合应答
Predictors for combined response in HBeAg-positive chronic hepatitis B patients with adefovir dipivoxil treatment
GAO Hai-bing，PAN Chen，LIN Ming-hua，ZHOU Rui，ZHENG Ling，LIN Tai-jie，XU Li-jun，YUAN Jin-jin，FANG Jian-kai.Department of Liver Diseases，Fuzhou Infectious Diseases Hospital，Affiliated Infectious Diseases Hospital of Fujian Medical University，Fuzhou 350025，China
Abstract:Objective To investigate the predictive factors of combined response in HBeAg-positive chronic hepatitis B(CHB) patients with adefovir dipivoxil(ADV) treatment，which included serum levels of tumor necrosis factor α (TNF-α)，polymorphisms in TNF-α gene promoter region at positions -238 and -308，genotypes and subgenotypes of hepatitis B virus (HBV)，and so on.Methods 203 HBeAg-positive CHB patients were recruited for research and administered with ADV(Mingzheng) 10 mg once a day for 48 weeks.The gene polymorphisms in TNF-α promoter region at positions -238 and -308 were determined by the restriction fragment length polymorphism assay of polymerase chain reaction products(PCR)，and the serum baseline levels of TNF-α were examined by enzyme linked immunosorbent assay.HBV genotypes were assayed by real-time fluorescent quantitative PCR or sequencing HBV S gene by which HBV subgenotypes could be determined.Logistic regression was used to identify some factors to forecast the efficacy.Results The rate of HBV DNA negativity，alanine aminotransferase (ALT) normalization，HBeAg loss and seroconversion，and response in patients at the treatment times of 24 and 48 weeks was 31.5%,59.1%,15.8%,8.9%,13.3% and 58.6%,78.3%,29.6%,16.7%,25.6% respectively.Patients who achieved response at week 24 were found to have higher baseline levels of TNF-α and ALT，and lower baseline loads of HBV DNA than those with non-response(P＜0.05).Meanwhile response at week 48 were observed more often in patients with higher rate of HBeAg loss and seroconversion at week 24，higher baseline levels of TNF-α，and lower baseline loads of HBV DNA than those with non-response(P＜0.05).Conclusions The baseline levels of TNF-α，ALT and HBV DNA may be predictors for response at week 24 in HBeAg-positive CHB patients with ADV treatment.Also the rate of HBeAg loss and seroconversion at week 24，baseline levels of TNF-α and HBV DNA may forecast response at week 48.
Key words:Hepatitis B，chronic； Tumor necrosis factor-alpha； Genotype； Adefovir dipivoxil；Combined response
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