阿德福韦酯治疗HBeAg阳性慢性乙型肝炎病毒学应答的预测因素分析  

Predictors of virological response in HBeAg-positive chronic hepatitis B patients treated with adefovir dipivoxil

作　　者：林明华[1] 高海兵[1] 潘晨[1] 林太杰[1] 郑玲[1] 原津津[1] 方建凯[1] 周锐[1] 许利军[1] 

机构地区：[1]福建医科大学附属传染病医院肝病科,福州350025

出　　处：《中华传染病杂志》2011年第8期468-473,共6页Chinese Journal of Infectious Diseases

基　　金：福州市社会发展科技项目（2008-s-74）

摘　　要：目的探讨阿德福韦酯（ADV）治疗HBeAg阳性慢性乙型肝炎（CHB）患者病毒学应答的预测因素。方法对203例HBeAg阳性CHB患者采用ADV10mg／d治疗48周，PCR-限制性片段长度多态性检测TNF-α-238及TNF-α-308位点基因多态性，ELISA测定基线血清TNF-α水平，荧光定量PCR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ADV治疗24周和48周时HBV DNA转阴率、ALT复常率、HBeAg转阴率及转换率、联合应答率分别为31．5％（64／203）、59．1％（120／203）、15．8oA（32／203）、8．9％（18／203）、13．3％（27／203）和58．6％（119／203）、78．3％（159／203）、29．6％（60／203）、16．7％（34／203）、25．6％（52／203）。HBV基因型B、TNF-a-308G／A基因型、较高水平基线ALT及较低载量基线HBV DNA易于24周时HBV DNA转阴[OR=0．405，95％CI（0．191-0．859），P=0．019；OR=0.292，95％CI（0.132～0．643），P=0．002；OR=0．933，95％CI（0．989～0．997），P〈0．01；OR=2．089，95％CI（1．412～3．092），P〈0．01]；24周HBVDNA高转阴率、较高水平基线ALT有利于48周时HBV DNA转阴EOR=0．029，95％CI（0．007～0．126），P〈0．01；OR=0．995，95％CI（0.991～0.999），P=0．016]。结论HBeAg阳性CHB患者ADV治疗24周病毒学应答的预测因素是HBV基因型、TNF-α-308基因型、基线ALT水平及HBV DNA载量；48周的预测因素是24周HBV DNA转阴率、基线ALT水平。Objective To investigate the predictive factors of virological response in HBeAg- positive chronic hepatitis B （CHB） patients treated with adefovir dipivoxil （ADV）. Methods A total of 203 HBeAg-positive CHB patients treated with ADV （Mingzheng） 10 nag once daily for 48 weeks were recruited. The gene polymorphisms at positions-238 and-308 in tumor necrosis factor （TNF）-α promoter region were determined by the restriction fragment length polymorphism assay of products amplified using polymerase chain reaction （PCR-RFLP）. The serum levels of TNF-α at baseline were measured by enzyme linked immunosorbent assay （ELISA）. Hepatitis B virus （HBV） genotypes were tested by real-time fluorescent quantitative PCR and HBV subgenotypes were tested by HBV S gene sequencing. Factors related to ADV response were determined by Logistic regression analysis. Results The HBV DNA negative rate, alanine aminotransferase （ALT） normalization rate, HBeAg loss rate and seroconversion rate, and combined response rate at week 24 and 48 of treatment in 203 patients were 31.5% （64/203）, 59. 1% （120/203）, 15.8% （32/203）, 8.9% （18/203）, 13.3% （27/203） and 58.6% （119/203）, 78.3% （159/203）, 29.6% （60/203）, 16.7% （34/203）, 25.6% （52/203）, respectively. HBV DNA negative rate at week 24 was higher in patients with HBV genotype B, that was higher in patients with TNF-α-308G/A genotype, and that was higher in patients with higher baseline ALT level or lower baseline HBV DNA level COR = 0. 405,95 % CI （0. 191 - 0. 859 ）, P = 0. 019;OR=0. 292,95%CI（0. 132-0. 643）,P=0. 002;OR=0. 933,95%CI（0. 989-0. 997）,P= 0.01 ;OR=2. 089,95%CI （1. 412-3. 092） ,P〈0.01]. Meanwhile, HBV DNA negative rate at week 48 were higher in patients with higher HBV DNA negative rate at week 24 or higher baseline ALT level [OR=0. 029,95%CI（0. 007-0. 126）, P〈0. 01;OR= 0. 995,95%CI（0. 991 - 0. 999）, P= 0. 0161. Conclusions HBV genotype, TNF-α-308 genotype, baseline levels of ALT and H

关 键 词：肝炎 乙型 慢性 阿德福韦酯 肝炎e抗原 乙型 肿瘤坏死因子Α 肝炎病毒 乙型 基因型 DNA 病毒 

分 类 号：R51[医药卫生—内科学]