阿德福韦酯联合恩替卡韦治疗阿德福韦酯耐药的乙型肝炎肝硬化疗效分析耐药的乙型肝炎肝硬化疗效分析

Clinical investigation of entecavir combined with adefovir dipivoxil in the treatment of adefovir - resistanthepatitis B cirrhosis

目的 探讨阿德福韦酯联合恩替卡韦治疗阿德福韦酯耐药的乙型肝炎（乙肝）肝硬化的疗效。 方法 选择乙肝肝硬化患者１２５例，初始治疗出现阿德福韦酯耐药，根据治疗方法不同分为两组，治疗组 ６７例予以恩替卡韦联合阿德福韦酯抗病毒治疗，对照组５８例予以恩替卡韦单药替换治疗。比较两组治疗后 １２周、２４周、４８周丙氨酸氨基转移酶（ＡＬＴ）复常率，乙型肝炎病毒（ＨＢＶＤＮＡ）转阴率，乙型Ｅ抗原（ＨＢｅＡｇ） 转换率及ＣｈｉｌｄＰｕｇｈ评分。结果 治疗后１２周、２４周、４８周，治疗组ＡＬＴ复常率分别为６５．５％、８１．０％、 ９６６％，ＨＢＶＤＮＡ阴转率分别为６２．０％、６９．０％、７７．６％，ＨＢｅＡｇ转阴率分别为０．０％、０．０％、１７．２％。对照 组ＡＬＴ复常率分别为５８．２％、７７．６％、９４％，ＨＢＶＤＮＡ阴转率分别为５５．２％、５９．７％、７６．１％，ＨＢｅＡｇ转阴率 分别为０．０％、０．０％、１９．４％；治疗后１２周、２４周，治疗组ＡＬＴ复常率及ＨＢＶＤＮＡ转阴率均高于对照组，差 异均有统计学意义（治疗后１２周ＡＬＴ复常率χ２ ＝１４．６４，治疗后２４周ＡＬＴ复常率χ２ ＝８．２３，治疗后１２周 ＨＢＶＤＮＡ阴转率χ２＝４．５７，治疗后２４周ＨＢＶＤＮＡ阴转率χ２ ＝１４．２４，均Ｐ＜０．０５）。两组治疗后１２周、 ２４周、４８周ＨＢｅＡｇ转换率差异均无统计学意义（均Ｐ＞０．０５）。治疗后４８周，治疗组ＣｈｉｌｄＰｕｇｈ评分为（６．０５± ２．１１）分，低于对照组的（７．６７±１．１２）分，差异有统计学意义（ｔ＝１．８９，Ｐ＜０．０５）。两组不良反应发生率差异 无统计学意义（Ｐ＞０．０５）。结论 阿德福韦酯联合恩替卡韦对阿德福韦酯耐药的乙肝肝硬化患者ＡＬＴ复常 率、ＨＢＶＤＮＡ转阴率具有较好的疗效，对肝硬化ＣｈｉｌｄＰｕｇｈ评分有改善，值得临床推广使用。

Objective Toinvestigatetheclinicaleffectofentecavir（ETV）combinedwithadefovirdipivoxil （ADV）inthetreatmentofadefovir-resistanthepatitisBcirrhosis.Methods 125casesoflivercirrhosiswith adefovir-resistantcewereselected,theyweredividedintotwogroups.Thetreatmentgroupincluded67caseswho receivedthecombinedtherapywithETVandADV.Thecontrolgroupincluded58caseswhoweretreatedwithETV. TheALTnegativerate,HBV-DNAnegativerate,HBeAgconversionrate,liverfunctionChild-pughscoreconversion rateswerecomparedbetweenthetwogroupswithin12,24,48weeks.Results Aftertreatmentfor12,24,48weeks, inthetreatmentgroup,theALTnegativerateswere65.5%,81.0%,96.6%,respectively,theHBV-DNAnegative rateswere62.0%,69.0%,77.6%,respectively,theHBeAgconversionrateswere0.0%,0.0%,17.2%,respectively. TheALTnegativerateandHBV-DNAnegativerateofthetreatmentgroupwerehigherthanthoseinthecontrol groupwithin12and24weeks,thedifferenceswerestatisticallysignificant（ALTnegativerateafter12and24weeks, χ2=14.64,8.23;HBV-DNAnegativerateafter12and24weeks,χ2=4.57,14.24）.TheHBeAgconversionrate hadnostatisticallysignificantdifferencebetweenthetwogroupsatanytime.Aftertreatmentfor48weeks,theChild-pugh scoreofthetreatmentgroupwas（6.05±2.11）points,whichwassignificantlylowerthan（7.67±1.12）pointsofthe controlgroup（t=1.89,P〈0.05）.Theincidencerateofadversereactionsbetweenthetwogroupshadnostatistically significantdifference（P〉0.05）.Conclusion Entecavircombinedwithadefovirdipivoxilinthetreatmentofpatients withhepatitisBcirrhosishasgoodeffectontheALTnegativerate,HBV-DNAnegativerate.Itisworthyofclinical application.