最新慢性HCV肝炎抗病毒疗效预测及临床教学讲义PPT课件.ppt

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1、慢性HCV肝炎抗病毒疗效预测及临床BcellCD8+CTLHepatocyteCD4+ThcellYYYYYNKNKTcellsImmuneresponsetoHCVinfection:Rolelargelyunknown-early,vigorous,multi-specificresponse-strongNS3-responseinresolvingacuteHCV-TH1inrecovery-TH2inchronic-vigorous,multi-specificresponse-CTLexerts

2、omecontrolonviralloadantibodiestomoststructuralandnon-structuralviralproteinsaremadeBiologicalActivitiesofIFNSignalISGIFN-inducedproteinInhibitionofviralreplicationInhibitionofCellGrowthRegulationofCelldifferentiationActivationofImmuneSystemReducedcapacity

3、ofmatureDCfromHCVpatientstoinduceallogeneicTcellproliferation.Bainetal.Gastroenterology120:51-524,2001AntagonismofIFNbyHCVproteinsIFNProteinKinasePKRinactiveInitiationFactoreIF-2aPhosphorylatedInitiationFactoreIF-2aPPhosphatase(soluble)PimRNAtranslationinh

4、ibitionProteinKinasePKRactivedsRNAssRNAHCVE2HCVNS5A影响IFN抗HCV治疗的因素性别年龄种族体重感染HCV时间细胞免疫状态、肝脏纤维化程度、脂肪变程度、胰岛素抵抗HCV基因型、准种、病毒含量ISDR变异、E2胞膜蛋白与eIF-2a的同源性病毒下降的速度以前是否治疗治疗药物、剂量、给药方法、联合用药PP人群197例临床特征临床特征和病毒学指标数值男/女134/63年龄≥50/<50岁49/148HCV感染途径输血/非输血130/67IF

5、N治疗史治疗后复发/IFN初治53/144血小板记数163.3±72.87AST/ALT比值≥1/<122/175HCVRNA载量≥8×105IU/ml97<8×105IU/ml100HCV基因型基因1型154非基因1型43治疗药物Roferon-A98Pegasys99各临床特征患者和病毒学指标的ETVR和SVR临床特征和病毒学指标ETVR(%)SVR(%)性别男/女54.48/57.1430.60/23.81年龄≥50/<50岁51.02/56.7620.41/31.08HCV感染途径输血/非输血53.

6、03/60.0026.52/32.31IFN治疗史治疗后复发/IFN初治56.60/54.8633.96/26.39AST/ALT比值≥1/<154.55/55.4331.82/28.00HCVRNA载量(IU/ml)≥8×105/<8×10553.61/57.0028.87/28.00HCV基因型基因1型/非基因1型53.90/60.4724.68/41.86治疗药物Pegasys/Roferon-A77.78/32.6540.40/16.33HCVRNA含量与基因型的相关性基因型例数.HCVRNA载量对

7、数值p值基因型数量单基因型感染1875.697±0.4710.573混合基因型感染185.761±0.346基因型基因1型1575.714±0.4500.527非基因1型485.666±0.498不同HCVRNA含量患者的生化和病毒学应答病毒载量应答方式≥8105IU/ml(134cases)<8105IU/ml(74cases)pvalue生化应答24周54(40.30%)38(51.35%)0.12448周58(43.28%)32(43.24%)0.996病毒应答ETVR74(55.22%)40(5

8、4.05%)0.871SVR38(28.36%)23(31.08%)0.680ETVR和SVR与患者临床特征和病毒学指标的独立相关性ETVRSVR临床特征标准误比值比(OR，95%CI)p值标准误比值比(OR，95%CI)p值性别0.3701.479(0.716-3.053)0.2900.3890.782(0.365-1.678)0.528年龄0.0160.978(0.949-1.009)0.1700.0160.