1、1.WHO.Hepatitis C.Fact sheet no.164.2.CDC.MMWR.1998;47(RR-19):1-39.3.CDC.Hepatitis C slide kit.September 25,2000.WHO.Wkly Epidemiol Rec.2000;75:18-19.3%3%（14 14 省省）2 23%3%（11 11 省省）2%3.8ECi S/CO 8或或报告报告报告报告报告报告报告报告报告报告PCR（市售或室内）（市售或室内）TMA(transcription mediated amplification)暴露后暴露后1 12 2周检测阳性周检测阳性 灵
2、敏度为灵敏度为 1050 IU/ml 感染中可能间隙性阳性感染中可能间隙性阳性 可能有假阳性和假阴性可能有假阳性和假阴性筛选与诊断实验的方法筛选与诊断实验的方法核酸定性检测（核酸定性检测（HCV RNA）PCR（市售或室内）（市售或室内）Branched-DNA 筛选与诊断实验的方法筛选与诊断实验的方法核酸定量检测（核酸定量检测（HCV RNA）HCV国际单位与拷贝数换算国际单位与拷贝数换算NGI SuperQuant:1 IU/mL=3.4 copies/ml (NGI Product License Application to FDA)Roche Amplicor Monitor v2.
3、0 1 IU/mL=0.9 copies/ml (Roche Molecular Systems)Cobas Amplicor Monitor HCV v2.0 1 IU/mL=2.7 copies/ml (Roche Molecular Systems)LCx HCV RNA Quantitative Assay 1 IU/mL=3.8 copies/ml (Abbott Diagnostics)Bayer bDNA 3.0:1 IU/mL=5.2 copies/ml (Bayer Development Group)STRADER DB,WRIGHT T,THOMAS DL,SEEFF L
4、B.Diagnosis Management and Treatment of Hepatitis C.AASLD PRACTICE GUIDELINESHCV RNA检测范围检测范围2202002,00020,000200,0002,000,000HCV RNAIU/mL1.Roche Diagnostics.Methods Manual.2.National Genetics Institute.SuperQuant.3.Baker MB.HCV RNA 3.0 Quantitation by bDNA.4.Bartnof HS,Herrera J.AASLD Annual Meeting
5、.1999.615 IU/mL7.7 106 IU/mLBayer bDNA 3.0SuperQuant100 拷贝拷贝/mL108 拷贝拷贝/mLBayer TMA10 IU/mLAMPLICOR HCV MONITOR Test 2.0600 IU/mL500,000 IU/mLAMPLICORHCV Test 2.050 IU/mL线形范围线形范围动态范围动态范围定性检测定性检测定量检测定量检测SuperQuant30 IU/mL1.47 106 IU/mL5 106 IU/mL抗抗-HCV“游离游离”抗原抗原时间时间HCV 感染过程感染过程早期检测早期检测“筛查筛查”“总总”抗抗原原(
6、抗体结合抗体结合)“总总”抗原抗原诊断用诊断用日日年年 InfectionHoffmann-La Roche.Data on file.Updated from Hadziyannis SJ.EASL Annual Meeting.2002.86%(n=390)75%(n=184)SVR“完全剂量完全剂量”(n=245)67%(n=261)所有患者所有患者14%(n=63)3%(n=3)聚乙二醇干扰素聚乙二醇干扰素-2a/RBV:12周预测周预测 所以患者所以患者*(n=453)阴性预测值阴性预测值=97%*PCR 检测检测 HCV RNA 阴性或下降大等于阴性或下降大等于2 log早期病毒学
7、应答早期病毒学应答*Roche data on file.Updated from Fried DDW.2001.YesNoALT“正常”的丙肝患者Shiffman ML,et al.J Infect Dis 2000;182:1595-1601.病毒学应答率病毒学应答率(%患者）患者）10080604020030%72%70%52%0%0%A组组(N=212)B组组(N=210)C组组(N=69)组间比较组间比较:A vs C:P001;B vs C:P001;B vs A:P2 x 106 copies/mL基因型基因型 1 型型基因型基因型 2/3 型型Randomization 2:1
8、:1:2(n=950)180 gFollow-upStudy Week04824961236607284Follow-up360 gplus RBV*180 gplus RBV*Follow-up360 gplus RBV*180 g 180 gFollow-upplus RBV*RBV dose:1000/1200 mg/dayHCV RNA 50 IU/mL(qualitative)or HCV RNA 600 IU/mL(quantitative)or 2-log10 drop RBV 1000/1200 mg/天天(weight-adjusted)标准剂量组标准剂量组诱导剂量组诱导剂量
9、组210/469291/473患者患者(%)4562*p0.0001n=01020304050607050/133Patients(%)HCV RNA 50 IU/mL(qualitative)or HCV RNA 600 IU/mL(quantitative)or 2-log10 drop RBV 1000/1200 mg/day(weight-adjusted)标准剂量组标准剂量组159/3333848肝硬化肝硬化无肝硬化无肝硬化n=60/11950诱导剂量组诱导剂量组231/35266010203040506070Marcellin P,et al.AASLD 2005.Poster p
10、resentation 1174HCV RNA 600 IU/mL(quantitative)or 2-log10 drop in HCV RNAMarcellin P,et al.AASLD 2005.Poster presentation 1174Marcellin P,et al.AASLD 2005.Poster presentation 1174Response in Patients Without RVR at Week 4Patients,%EOTSVRRegimen A6316Regimen B7023Regimen C 5636Regimen D6344Regimen BP
11、egIFN-alfa 2a+RBV 1000/1200 mg/d24 weeksRegimen CPegIFN-alfa 2a+RBV 800 mg/d24 weeks慢性丙型肝炎慢性丙型肝炎基因基因1型型N=729Regimen BPegIFN-alfa 2a+RBV 1000/1200 mg/d48 weeksRegimen DPegIFN-alfa 2a+RBV 800 mg/d48 weeksResponse in Patients With RVR at Week 4Patients,%EOTSVRRegimen A9489Regimen B9788Regimen C 7373Reg
12、imen D9391Jensen D,et al.AASLD 2005.Abstract 1155.快速病毒学应答快速病毒学应答 4周时周时HCV RNA 50 IU/mL SVR(%)n=5433n=5630*n=878n=88Fried MW et al.N Engl J Med 2002.In press.单一治疗单一治疗联合治疗联合治疗010402030*P=0.001.Heathcote EJ et al.N Engl J Med.2000;343:1673-1680.50 patients previously treated with PegIFN/RBV for 12 week
13、s without 2 log10 drop in HCV RNA Patients retreated with CIFN 15 g QD+IFN-gamma 1b 50 g TIW(open label)for 48 weeksSerum HCV RNA assayed at 8,12,24,48,and 72 weeksResponse in black subgroup similar to total populationVirologic Response(%)Study PopulationWeek 12 HCV RNA(-)Week 24 HCV RNA(-)Week 48 H
14、CV RNA(-)Week 72 SVRTotal population,n=5040464634Black subgroup,n=2035404535P value.55.48.90.90Leevy C,et al.AASLD 2005.Abstract 1267.药物选择1.中国丙型肝炎防治指南，中国丙型肝炎防治指南，2003 1、联合治疗优于单药治疗、联合治疗优于单药治疗 2、PEG-IFN优于普通优于普通IFN 3、利巴韦林禁忌者，单用、利巴韦林禁忌者，单用IFN 治疗治疗 PEG-IFN 与利巴韦林联合治疗与利巴韦林联合治疗是目前最有效的方案是目前最有效的方案11.中国丙型肝炎防治指南，中国丙型肝炎防治指南，2003年年药物选择药物选择治疗的主要目标：治疗的主要目标：清除或持续抑制体内的清除或持续抑制体内的HCV，获得获得SVR1
