丙肝治愈丙肝的最佳选择

派罗欣治愈中国丙肝患者的最佳选择,根据派罗欣两项III期临床研究结果确立了标准丙肝治疗方案,Fried研究,Hadziyannis 研究,2004年美国指南推荐慢性丙肝治疗方案,ALT 正常的病人如肝活检有活动性病变应采取治疗，如无炎症反应或病变轻微则应定期随访检查。,AASLD guideline 2004,2004 AASLD 指南, the design of the peginterferon alfa-2a study was the only one capable of determining that a treatment duration of 6 months is sufficient for persons infected with HCV genotypes 2 or 3. Peginterferon -2a的研究设计是唯一能够确定基因2/3型丙肝患者只需治疗6个月（24周）的研究。,研究,比值比，95%CI,Sinha 2004,1.05 0.62,1.79,Yenice 2006,1.38 0.79,2.43,Scotto 2008,1.09 0.55,2.16,Rumi 2009,1.22 1.04,1.42,McHutchison 2009,1.05 0.96,1.15,Ascione 2009,1.26 1.06,1.51,Kolakowska 2008,1.07 0.85,1.34,Laguno 2009,1.09 0.79,1.52,总体结果(95% CI),1.11 1.04,1.19,P=0.004,0.5,1,2,PEG-IFN 2b,派罗欣,比值比，95%CI,Cochrane荟萃分析显示派罗欣的临床疗效显著较好,共有8项临床研究对比派罗欣方案与PEG-IFN alfa-2b方案的SVR率，包括4335例患者，最终结果显示：派罗欣的疗效显著更好 (P=0.004),Awad T, et al. Hepatology. 2010; 51(4): 1176-84.,0,10,20,30,40,50,60,70,80,SVR (%),派罗欣 临床实践印证III期研究结果,n=,1. Manns M, et al. Lancet 2001; 358: 958. 2. Lee S, et al. Aliment Pharmacol Ther 2006; 23: 397 3. Fried M, et al. N Engl J Med 2002; 347: 975 . 4. Hadziyannis S, et al. Ann Intern Med 2004; 140: 3465. Zeuzem S, et al. J Hepatol 2005; 43: 250. 6. Zehnter E, et al. 56th AASLD 2005; Abstract 1233,所有基因型,73%,738,55%,334,66%,1341,56%,2002,Fried3,453,2006,Zeuzem5,2006,Zehnter6,60%,2005,Zeuzem6,52%,52%,2006,Ferenci5,61%,381,2006,Zehnter7,派罗欣 临床实践印证III期研究结果基因1型,Manns M, et al. Lancet 2001; 358: 958. 2. Fried M, et al. N Engl J Med 2002; 347: 975. 3. Diago M, et al. 41st EASL 2006; Abstract 567.4. Hadziyannis S, et al. Ann Intern Med 2004; 140: 346. 5. Ferenci P, et al. J Hepatol 2006; 44: 275. 6. Zeuzem S, et al. J Hepatol 2005; 43: 250. 7. Zehnter E, et al. 56th AASLD 2005; Abstract 1233,0,10,20,30,40,50,60,70,80,46%,2002,2004,SVR (%),n= 348 298 271 95 90,Fried2,Hadziyannis4,42%,2001,Manns1,Peg-IFN-2b (12KD) +RBV,派罗欣 + RBV,48%,475,2006,Diago3,Von Wagner4,1. Zeuzem S, et al. J Hepatol 2004; 40: 993. 2. Mangia A, et al. N Engl J Med 2005; 352: 26093. Lee S, et al. Aliment Pharmacol Ther 2006; 23: 397.4. Von Wagner M, et al. Gastroenterology 2005; 129: 5225. Hadziyannis S, et al. Ann Intern Med 2004; 140: 346. 6. Zehnter E, et al. 56th AASLD 2005; Abstract 12337. Zeuzem S, et al. J Hepatol 2005; 43: 250,派罗欣 临床实践印证III期研究结果基因2/3型,PROPHESYS研究：临床实践证实，派罗欣是预测患者获得SVR的独立预测因素之一,全球多中心，初治慢性丙型肝炎单一感染患者的Cohort研究，共入选7900例患者，所有患者治疗均按各国日常诊疗常规而开展,2012 APASL poster. PP13-042,Ethnic origin:,Platelet count:,ALT ratio:,Asian vs White,White vs Black,White vs Hispanic,White vs Other, 180 vs 140 x 109/L, 180 vs 140 to 3 vs 1,3 vs 1 to 3,Baseline HCV RNA per 1-log decrement,Hepatic fibrosis:,AST ratio 1.5 vs 1.5,Peginterferon alfa-2a (40KD) vs alfa-2b (12KD),Age per 10-year decrease,BMI per 1-unit decrease,Hepatic steatosis:,No cirrhosis vs cirrhosis,not assessed/missing vs cirrhosis,no vs yes,yes vs not assessed/missing,0.1,1,10,0.1,1,10,SVR less likely,Odds ratio (95% CI),SVR more likely,Odds ratio (95% CI),2.04 (1.09-3.80),2.56 (1.66-3.95),1.93 (1.38-2.69),1.03 (0.71-1.49),1.96 (1.58-2.43),1.09 (0.92-1.30),1.58 (1.23-2.04),1.43 (1.18-1.73),1.54 (1.42-1.67),1.47 (1.24-1.75),1.34 (1.10-1.64),1.42 (1.20-1.69),1.35 (1.02-1.78),1.15 (1.08-1.22),1.02 (1.01-1.04),1.16 (0.98-1.37),1.08 (0.91-1.28),Cochrane荟萃分析显示导致停药的不良事件发生率派罗欣治疗组更低,Awad T, et al. Hepatology. 2010; 51(4): 1176-84.,Study or Subgroup,Events,Events,Total,Peg 2a,Peg 2b,Total,Weight,Risk Ratio,Risk Ratio,Year,IV,Random, 95% CI,IV,Random, 95% CI,Bruno 2004,Sinha 2004,Berak 2005,Yenice 2006,Sliva 2006,Di Bisceglie 2007,Scotto 2008,McHutchison 2009,Rumi 2009,Laguno 2009,Ascione 2009,0,10,0,10,0,3,3,2,2,10,135,16,12,4,24,116,40,18,189,71,1035,212,96,160,1,18,3,3,121,40,4,18,11,191,8,227,17,7,22,72,2035,219,86,160,1.8%,5.9%,6.2%,6.0%,6.4%,12.5%,22.9%,15.7%,12.3%,10.3%,Not estimable 2004,0.25 0.01, 5.88 2004,1.04 0.21, 5.06 2005,0.18 0.06, 0.52 2009,1.00 0.21, 4.66 2006,0.50 0.10, 2.40 2006,0.18 0.04, 0.82 2007,1.27 0.53, 3.03 2008,1.17 0.96, 1.43 2009,0.97 0.50, 1.87 2009,1.54 0.63, 3.72 2009,Total (95% CI),1971,2970,100.0%,0.79 0.51, 1.23,Total events,187,303,Test for overall effect: Z = 1.04 (P = 0.30),Heterogeneity: Tauz =0.21; Chiz = 19.79, df = 9 (P = 0.02); Iz = 55%,0.1,0.2,0.5,1,2,5,10,Favors peg2b,Favors peg2a,中国丙肝防治指南慢性丙肝标准治疗方案,PEG IFN a-2a 180mg +利巴韦林1000mg/d 48周,12周早期病毒学反应,=2log HCV RNA,2106拷贝/ml,中国丙肝防治指南慢性丙肝标准治疗方案,治疗方案： PEG- IFN -2a 180g，每周1次，联合应用利巴韦林 800 mg/d，治疗24周。,注：不能耐受利巴韦林者：可单用PEG-IFN ,中国丙肝防治指南,基因非1型或(和)HCV RNA 2 106 拷贝/ml,研究表明宿主IL28B与SVR相关,Ge D et al. Nature 2009,Genetic variation in IL28B (rs 12979860),IL28B polymorphism and SVR,SVR (%),Non-SVR (%),Figure 1 Percentage of SVR by genotypes of rs12979860. Data arcPercentages + s.e.m.,中国HCV基因型的分布与东亚人群相似而有别于西亚和南亚的部分地区,中国2HCV-1:56.9%HCV-2:29.4%HCV-3: 8.9%HCV-6 :4.8%,中东HCV-1:2%HCV-2:91%Other:7%,印度HCV-1:14%HCV-2/3:73%Other:14%,东南亚HCV-1: 74%HCV-2:2-23%,台湾HCV-1:53%HCV-2:40%Other:8%,日本HCV-1:67%HCV-2/3:31%Other:2%,韩国HCV-1:68%HCV-2:25%Other:8%,澳门，越南，香港HCV-1:50%HCV-2/3:15%Other:35%,澳大利亚/新西兰HCV-1:52%HCV-2/3:41%Other:8%,1. Yu ML, Chuang WL. J Gastroenterol Hepatol 2009;24:3363452. Wei L, et al. Data on file,Ge D. Nature 2009. Nefdhal N. Hepatol 2011.,IL28基因多态性与不同人种的病毒应答差异,SVR (%),rs 12979860 C-allele frequency,10,30,50,70,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,African-Americans,Hispanics,European-Americans,East Asians,*,IL28B,IL28A,rs12980275,rs8105790,rs11881222,rs8103142,rs28416813,rs4803219,rs12979860,rs8099917,rs7248668,IL28B Overall Distributions in China,CC: 84.1%,TT: 0.6%,rs12979860,CC allet: More favorable to treatment response,2011 AASLD meeting,中国患者IL28与病毒应答之间的关系,Chen. Xinyue. AASLD 2011,Rs12979860 genotype,Patients with a cEVR, %,100,90,80,70,60,50,40,30,20,10,0,CC,CT,96.9,57.1,p0.001,中国丙肝患者基线特征与欧美患者的比较,*IU/ml=0.854拷贝数/ml+0.538,2002 M.Fried. NEJM; Chen. Xinyue. AASLD, 2011,中国基因1型丙肝患者治疗应答情况与欧美患者的比较,2008 Lee. S. Antiviral ther; Chen. Xinyue. AASLD 2011,中国患者整体属于治疗疗效较好的人群，是否普通干扰素能够同样达到相似疗效？,派罗欣治疗中国慢性丙肝初治患者疗效显著优于普通干扰素,治疗慢性丙肝初治患者,派罗欣 +RBV,普通干扰素+RBV,1. 中华实验和临床病毒学杂志 2006; 20(2): 42-5. 2.广东医学 2007; 28(12): 2016-7. 3.中国感染控制杂志 2009; 8(2): 107-9. 4.临床荟萃 2008; 23(1): 49-50. 5.中国临床医学 2007; 14(6): 815-6. 6.华西医学 2009; 24(3): 646-8. 7.中国基层医药 2009; 16(2): 221-2.,SVR率 RR, 95% CI,IFN+RBV更好,PEG-IFN+RBV更好,0.5,1,2,5,10,派罗欣 +RBV vs. 普通INF+RBV,亚组汇总分析,P0.0001,2.26 1.56, 3.26,荟萃分析,PEG-IFN -2b+RBV vs. 普通INF+RBV,亚组汇总分析,P=0.23,总体分析,P=0.003,1.21 0.89, 1.63,1.76 1.21, 2.56,PEG-IFN+RBV vs. 普通INF+RBV,中国慢性丙肝患者疗效荟萃分析仅有派罗欣显著优于普通IFN,数据来源：美国MEDLINE、中国知网（CNKI）；共有7项研究符合筛选标准，患者总数398例，所有患者均为华裔人种,Zhao SH, et al. Int J Clin Pract, 2009; 63(9): 1334-9.,派罗欣方案治疗既往普通IFN复发患者可以获得理想的疗效,派罗欣方案是既往干扰素治疗无应答患者获得SVR的阳性预测因子,Camm C, et al. J Hepatol. 2009; 51(4): 675-81.,纳入14篇全文论著，共3898例无应答再次治疗患者，其中11项为多中心研究,荟萃回归分析,0,10,20,30,21.2,13.4,派罗欣组,PEG-IFNalfa-2b组,P=0.029,SVR(%),强化治