特殊人群抗病毒治疗及药物进展.ppt

*APOBEC蛋白载脂蛋白*ForLambda,14/80patients（18%）hadHBeAg血清学转换at周48（endoftreatment）.Subsequently,7ofthesepatientresponseswerelost（4seroreverted,2initiatednuctherapy,and1waslostto随访）buttherewere4newpatient血清学转换s;thereforeby周24post-dosingtheHBeAg血清学转换rateforLambdawas11/80（14%）Foralfa,14/83patients（17%）hadHBeAg血清学转换at周48（endoftreatment）.Subsequently,4ofthesepatientresponseswerelost（3serorevertedand1waslostto随访）buttherewere15newpatient血清学转换s;thereforeby周24post-dosingtheHBeAg血清学转换rateforalfawas25/83（30%）RatesofHBeAglossingeneralalsoparalleledratesofHBeAg血清学转换（15%and33%at周24post-dosingforLambdaandalfa,respectively）********TargetedmolecularimmunogenorTarmogen*Interferonisarecombinantimmunemodulatorthatwasfirstapprovedasinterferonalfa-2bin1992.Pegylatedinterferonalfa-2a,whichwasapprovedin2005,allowsaconvenientonce-周lydosingthatmakesittheinterferonofchoice.Interferonsmustbeadministeredwithasubcutaneousinjection.Inadditiontoitsimmunomodulatoryfunction,interferonhasdirectantiviralactivity,althoughtheexacttargetagainstHBVreplicationisunknown.*Howtoenhanceresponseratethroughcombinationtherapy?What’sthebestcombinationtherapy?ThediscussionaboutIFNand核苷（酸）类似物combinationhasneverceased.ThefollowingclinicaltrailsonIFNand核苷（酸）类似物combinationcannotprovidesufficientevidence,provingthatcombinationtherapycanbringmorebenefit.***针对cccDNA的治疗包括干扰素，淋巴毒素β受体（LTβR）激动剂，RNA靶向（RNA干扰和外部引导序列）锌指核酸酶和磺酰胺类化合物：直接破坏cccDNA，抑制rcDNA转换为cccDNA，以及针对cccDNA的表观遗传控制CRISPR：采用针对DNA保守区域的序列特异性的靶向RNA，引导核酸酶在此位点切割DNA，CRISPR策略有望用于人体基因治疗，并有助于针对HBV之类具有稳定病毒基因组的病毒感染传统的抗病毒治疗，尤其是新药的上市，已经可以把HBVDNA控制在不可检测的水平，但是这些患者因为cccDNA存在复发的可能，在此基础上，如果联合cccDNA靶向治疗，有可能达到感染肝细胞的免疫清除。Kennedyetal.Virology2015DrugDiscoveryTodayVolume20,Number5,May2015cccDNA降解/沉默/清除CRISPR:规律成簇间隔