抗乙肝病毒核苷类药物课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,抗乙肝病毒核苷药物一,转换治疗,抗乙肝病毒核苷药物一,1,优选还是首选?,Nuc-naive patients can be treated with IFNa(IB),Peg IFN (IA), ETV(IA), TDF(IA), ADV(IB),LdT,(IB)or LAM(B). Thymosin-a can also be used,B). ETV or TDF is the preferred Nuc,Consider duration, cost, rapidity of action and,adverse effects,优选还是首选?,2,EASL的意见,Entecavir and tenofovir are potent hBv inhibitors with a high,barrier to resistance 67,70, 78, 85, 92, 123(Fig. 1). Thus, they can,be confidently used as first-line monotherapies |1|(A1),The other three NAs may only be used in the treatment of CHB,if more potent drugs with high barrier to resistance are not avail,ble or appropriate(A1). Lamivudine is an inexpensive agent, but,engenders very high rates of resistance with long-term mono,therapy 124-127. Adefovir is less efficacious and more,expensive than tenofovir, engendering higher rates of resistance,170, 85, 100 Telbivudine is a potent inhibitor of HBV replication,but, due to a lower barrier to resistance a high incidence of resis-,tance has been observed in patients with high baseline HBV DNA,levels and in those with detectable hbv dna after 6 months of,therapy 68,77: resistance rates to telbivudine are relatively,low in patients with low baseline viremia(2x 10IU/ml for,HBeAg-positive and 2 x 10 IU/ml for HBeAg-negative patients,EASL的意见,3,APASL与EASL的分歧,无论是AMdT治24周时的部分应答,还是ADV治疗48周时的部分应答,EASL,2019指南推荐的A1级方案均为换用更强效的无交叉耐药位点的药物(ET或TDF),In patients receiving lamivudine or telbivudine(drugs with a low,genetic barrier to resistance)with a partial virological response at,ek 24 or in patients receiving adefovir(moderately potent drug,that engenders relatively late emergence of resistance) with a partial,response at week 48, change to a more potent drug(entecavir or,tenofovir, preferentially without cross-resistance, is recommended,APASL,For primary treatment failure(mo 3)or suboptimal response(mo 6), stop and,switch to a more potent Nuc or add-on a Nuc without cross resistance if LAM,LdT or adv was used (IIIA),Easl.JhepaTol(2019),http:/ax.doi.org10.1076/jhep.2019.02.010,APASL与EASL的分歧,4,初治选择了高耐药或低效核苷类药物,LAM是第一个上市的抗乙肝病毒核苷类药物,迄今,仍然有大量慢性乙型肝炎患者使用着LAM,中国仍,然有大量患者继续初始使用LAM,而欧美和日本肝,病学会指南均把LAM和ADV确定为非一线药物。,中国现状与发达国家有同亦有别:,相同:,在没有抑制病毒更强、耐药率更低的药物时使用拉米夫定,区别,地区发展不平衡,经济条件决定了必须继续首选拉米夫定,患者不知晓,医生主导下单用LAM或ADV,很多地区初始联合使用LAM和ADV,初治选择了高耐药或低效核苷类药物,5,治疗48周病毒学应答不佳率很高,Week 24,Week 48,2az,55%,37%,24%,20%,LAM,ETs,Baseline,HBVDNA,9.574,9.577,897.0,9.67.6,8.66.9,ampertico P. Journal of Hepatology, 2009(50): 644-647,治疗48周病毒学应答不佳率很高,6,24周 HBV DNA3log,2年耐药率依然较高,HBeAg(+),HBeAg(-),L替比夫定,29,33to4,QL G,3 to 4,n=203146b7638379115175178157182916241023,治疗24周时血清 HBV DNA水平,Lai Cl, et al. 57th Annual Meeting of AASLD, 2019: Abstract 91,24周 HBV DNA3log,2年耐药率依然较高,7,早期应答不佳后续耐药危险很高,Table 2. On-treatment HBV DNA level and drug resistance at end of respective duration of therapy,Duration,HBeAg serostatus 3300,af treatment. weeks,Reference,Lamivudine,Positive,75创,telbivudine,Negative,00闐,Adefovir,Negative,2,7,cun-Fan Liao: Antiviral Therapy. 2009; 14: 13-22,早期应答不佳后续耐药危险很高,8,应答不佳者应在治疗中调整治疗方案,研究表明,核苷类药,物治疗早期应答不佳者,存,在潜在的耐药危险,需要在,治疗过程中调整治疗方案,这对那些由于经济因素初治,患者广泛选择拉米夫定的国,Yun Fan liaw,家(或地区)来说尤其应如,Review,Antiviral Therapy. 2009,此,Yun-Fan Liao: Antiviral Therapy. 2009; 14: 13-22,应答不佳者应在治疗中调整治疗方案,9,耐药可抵消抗病毒治疗的长期获益,n=215),变异(n=209)49%,蚁咝荆墚,13%,10,月,耐药可抵消抗病毒治疗的长期获益,10,抗乙肝病毒核苷类药物课件,11,抗乙肝病毒核苷类药物课件,12,抗乙肝病毒核苷类药物课件,13,抗乙肝病毒核苷类药物课件,14,抗乙肝病毒核苷类药物课件,15,抗乙肝病毒核苷类药物课件,16,抗乙肝病毒核苷类药物课件,17,抗乙肝病毒核苷类药物课件,18,抗乙肝病毒核苷类药物课件,19,抗乙肝病毒核苷类药物课件,20,抗乙肝病毒核苷类药物课件,21,抗乙肝病毒核苷类药物课件,22,抗乙肝病毒核苷类药物课件,23,抗乙肝病毒核苷类药物课件,24,抗乙肝病毒核苷类药物课件,25,抗乙肝病毒核苷类药物课件,26,抗乙肝病毒核苷类药物课件,27,抗乙肝病毒核苷类药物课件,28,抗乙肝病毒核苷类药物课件,29,抗乙肝病毒核苷类药物课件,30,抗乙肝病毒核苷类药物课件,31,抗乙肝病毒核苷类药物课件,32,抗乙肝病毒核苷类药物课件,33,抗乙肝病毒核苷类药物课件,34,抗乙肝病毒核苷类药物课件,35,抗乙肝病毒核苷类药物课件,36,抗乙肝病毒核苷类药物课件,37,抗乙肝病毒核苷类药物课件,38,抗乙肝病毒核苷类药物课件,39,抗乙肝病毒核苷类药物课件,40,抗乙肝病毒核苷类药物课件,41,抗乙肝病毒核苷类药物课件,42,抗乙肝病毒核苷类药物课件,43,抗乙肝病毒核苷类药物课件,44,抗乙肝病毒核苷类药物课件,45,抗乙肝病毒核苷类药物课件,46,抗乙肝病毒核苷类药物课件,47,抗乙肝病毒核苷类药物课件,48,抗乙肝病毒核苷类药物课件,49,抗乙肝病毒核苷类药物课件,50,抗乙肝病毒核苷类药物课件,51,抗乙肝病毒核苷类药物课件,52,抗乙肝病毒核苷类药物课件,53,抗乙肝病毒核苷类药物课件,54,抗乙肝病毒核苷类药物课件,55,