拉米夫定优化治疗的结局

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,贺普丁,优化治疗,的真实结局,内 容,为什么要优化治疗,优化治疗的由来,贺普丁优化治疗方案,贺普丁优化治疗方案的本钱效益,为什么要优化治疗,HBV DNA,下降不理想,血清转换率不高,应答不佳比例升高,停药后复发,.,Chang TT,et al.J Gastro Hepatol.2004;19:1276-1282.Lok AS et al.Gastroenterol.2003;125:1714-1722.Chang TT,et al.N Engl J Med.2006;354:1001-1010.Chang TT,et al.Hepatology.2006;44(suppl 1):229A.Marcellin P,et al.N Engl J Med.2003;348:808-816.Marcellin P,et al.Hepatology.2006;44(suppl 1):548A.Lai CL,et al,Hepatology.2005;42(suppl 1):748A.Lai CL,et al.Hepatology.2006;44(suppl 1):222A.Han S,et al.AASLD 2007.A938.,*,(ETV-022+ETV-901),较,ETV-022,研究的,HBeAg,血清转换率,31%,增加,16%(,第二年,).,长期治疗,只有约,50%,的患者可以实现,HBeAg,血清转换目标,50,47,40,29,22,0,20,40,60,LAM,ADV,ETV,LdT,1,2,3,4,5,治疗时间 年,患者,(%),患者,(%),80,100,47*,37,31,21,0,20,40,60,80,100,48,13,0,20,40,60,80,100,23,29,1,2,3,4,5,治疗时间 年,患者,(%),0,20,40,60,80,100,患者,(%),非头对头；,不同患者人群和研究设计,29,37,35,各种核苷类似物治疗后仍有相当比例的患者应答不佳,Pietro Lampertico et al.journal of Hepatology 2021;50:644-647 2.Nancy Leung et al.Hepatology 2021;49:72-79,10.3,9.5 7.4 9.5 7.7,HBV DNA,检测到的,比例,(%),LAM,LDT,ETV,68%,29%,55%,20%,55%,0,20,40,60,80,100,24,周,基线,HBV DNA,HBeAg(+),HBeAg(-),优化治疗策略的萌芽：早期应答与远期疗效,24,周时的,HBV DNA,12,周时的,HBV DNA,Farci P,et al.EASL 2005 Abstract 484.,2.Zeuzem S.EASL 2006.Abstract 51.,PCR,阴性患者,(%),0,20,40,60,80,100,PegIFN alfa-2a,治疗,48,周停药,24,周,1,HBeAg,阴性,400,c/mL,400,c/mL,n=,61,31,70,106,LAM,治疗,52,周,2,HBeAg,阳性,QL,QL,84,20,146,317,干扰素,NAs,203,57,83,107,146,63,79,165,178,18,16,10,157,20,24,LdT,104,周时,HBV DNA,转阴率,(%),61,40,20,88,78,63,20,73,60,28,7,68,60,25,5,82,0,10,20,30,40,50,60,70,80,90,100,4,4,LAM,HBeAg+,HBeAg,24,周时的,HBV DNA (log,10,copies/mL),Di Bisceglie A,et al,.,Hepatology,2006;44(Suppl 1):230A.Abstract 112.,优化治疗的根底：路线图现象Ldt 临床研究数据,*,*,LAM,治疗,24,周,HBVDNA,水平,或者,4log,的患者,5,年治疗结束时的疗效,Man-Fung Yuen,et al AASLD 2006,优化的本质：早期改善疗效，远期获益,0,20,40,60,80,100,对,LAM-R,cli,者,LAM,ADV,(2001,2003),对,LAM-R,vbk,者,LAM ADV,(2003,2005),35%,LAM,单药治疗,(1996,2001),LAM+ADV,应答者,LAM,单药治疗应答者,100%,HBV DNA 3.3 log cp/ml的患者%,治疗失败者,83%,Lampertico P,et al.,(EASL 2006).,J Hepatol,2006;44(2 Suppl):S186 Abstract 499.,N=124,5-年 治疗HBV DNA到达检测不出水平的比例演变,治疗方案优化的可能性,贺普丁,优化治疗的,策略与实践,2021版中国指南,预测疗效和优化治疗:,有研究说明，除基线因素外，治疗早期病毒学应答情况可预测其长期疗效和耐药发生率。国外据此提出了核苷酸类似物治疗慢性乙型肝炎的路线图概念，强调治疗早期病毒学应答的重要性，并提倡根据HBV DNA监测结果给予优化治疗。,基线优化,贺普丁,通过基线参数选择患者，,治疗5年预后好,基线,HBV DNA,10,9,copies/mL,ALT,2ULN,5,年,88%ALT,复常,82%HBeAg,血清转换,77%HBV DNA,10,4,copies/mL,76%,未出现耐药*,*,耐药定义为病毒突破患者中伴有YMDD变异,1.Liaw Y-F,Leung N,Kao J-H et al.Hepatol Int 2021;2:263-283.,2.Yuen M-F,Fung J,Seto W-K et al.Antivir Ther 2021;14:679-685,HBeAg,阳性患者,贺普丁,通过基线参数选择患者，,治疗2年预后好,基线,HBV DNA10,7,copies/mL,1,ALT,升高,1,2,年,67%,PCR,阴性,1,1.Gane E,Chen Y-C,Thongsawat S.Hepatol Int 2021;2:S37-S211(Abstract OL-108).,2.Lai C-L,Gane E,Liaw Y-F et al.New Eng J Med 2007;357:2576-88,HBeAg,阴性患者,疗效评估,贺普丁,优化治疗,方案疗效评估,时间点如何界定,根据基线参数分组,根据基线,HBV DNA,和,ALT,水平患者分为,3,组,HBV DNA,9 logs,拷贝,/mL,&,ALT,2 ULN,HBV DNA,9 logs,拷贝,/mL,&,ALT,2 ULN,HBV DNA,9 logs,拷贝,/mL,组,1:n=17,组,2:n=22,组,3:n=35,Fung JF,Lai Cl,Seto WK,et al.Combination of baseline HBV DNA and ALT level with on-treatment HBV DNA response,to select HBeAg-positive patients for lamivudine therapy.APASAL 2021 poster,贺普丁,基线优化结果,符合组1基线参数的患者，5年预后最正确：,ALT 复常:88.2%,HBV DNA 抑制 4 logs 拷贝/mL:76.4%(35 拷贝/mL:41.2%),HBeAg 血清转化:82.4%,YMDD 低变异率但仍不满意:35.5%,Fung JF,Lai Cl,Seto WK,et al.Combination of baseline HBV DNA and ALT level with on-treatment HBV DNA response,to select HBeAg-positive patients for lamivudine therapy.APASAL 2021 poster,贺普丁,基线优选和治疗,第,4,周,HBV DNA,应答,第一时间点：4周,截点值:4 logs 拷贝/mL,到达截点值的组 1 患者：5/17(29.4%),Fung JF,Lai Cl,Seto WK,et al.Combination of baseline HBV DNA and ALT level with on-treatment HBV DNA response,to select HBeAg-positive patients for lamivudine therapy.APASAL 2021 poster,贺普丁,基线优选和治疗,第,4,周,应答即治疗过程的进一步优化后治疗,5,年的结局,所有,患者均为,HBV DNA,检测不到,(35,拷贝,/mL),！,所有,患者均为,ALT,复常！,所有,患者均实现,HBeAg,血清转换！,所有,患者均无,YMDD,变异！,Fung JF,Lai Cl,Seto WK,et al.Combination of baseline HBV DNA and ALT level with on-treatment HBV DNA response,to select HBeAg-positive patients for lamivudine therapy.APASAL 2021 poster,这个节点过于严格，过于理想化！,贺普丁,基线优选和,第,24,周,HBV DNA,应答,第24周，截点值:3 logs 拷贝/mL,到达截点值的组 1 患者：10/17(58.8%),Fung JF,Lai Cl,Seto WK,et al.Combination of baseline HBV DNA and ALT level with on-treatment HBV DNA response,to select HBeAg-positive patients for lamivudine therapy.APASAL 2021 poster,贺普丁,基线优选和治疗,第,24,周,应答,即,治疗过程的进一步优化后,5,年预后情况,60%,HBV DNA,不可检测,(35,拷贝,/mL),80%,HBV DNA 3 logs copies/mL,90%,HBV DNA 4 logs copies/mL,100%,ALT,复常,90%,HBeAg,血清转化,10%,HBeAg,仍为阳性的患者出现,YMDD,变异,Yuen M-F,Fung J,Seto W-K,et al,.Combination of baseline HBV DNA and ALT levels with on-treatment HBV DNA response to select HBeAg-positive patients for lamivudine therapy.,Antivir Ther,14,，,679-685,24,周是更好的时间点！,贺普丁,优化治疗,方案,贺普丁优化治疗方案：,HBeAg,阳性患者,完全应答,1000copies/,mL,ALT,2ULN,和,HBV DNA1000copies/,mL,54