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,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,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,HBV再激活的发生,HBV再激活的发生,Hepatitis B:Some Sobering Facts,350 million people chronically infected,2 billion with evidence of,past or present infection,Country of origin is THE major risk factor,World Health Organization.Hepatitis B Fact Sheet.Centers for Disease Control and Prevention.CDC Health Information for International Travel 2012.New York:Oxford University Press;2012.,Prevalence of HBsAg,High 8%,Intermediate 2%to 7%,Low 3 10,5,copies/mL,Elevated if HBeAg positive,人口统计,Men women,Yeo W,et al.Hepatology.2006;43:209-220.,HBV再激活的危险因素恶性肿瘤HBV DNAYeo W,e,单纯抗HBc阳性的意义,表明曾暴露于HBV,通常保持终身，但也可以数年后消失,如果确实没有HBV危险因素，可以是假阳性,目前尚无治疗指南,再激活的风险,对大多数标准的实体肿瘤患者，风险较低,如果存在肝硬化应考虑预先治疗,如果采用下列治疗方案应考虑预先治疗,Rituximab,Bone marrow/stem cell transplantation,Manzano-Alonso ML,et al.World J Gastroenterol.2011;17:1531-1537.,单纯抗HBc阳性的意义表明曾暴露于HBVManzano-Al,其他因素引起HBV再激活,Roche B,et al.Liver Int.2011;31(suppl 1):104-110.,ImmunomodulatoryTherapy,Anti-TNF,(infliximab,adalimumab,etanercept),Antimetabolite,(methotrexate),Purine Analogues,(azathioprine/6mp),Steroids,(prednisone,budesonide),Other,(rituximab,cyclosporine),其他因素引起HBV再激活Roche B,et al.Li,Rituximab:一特殊的问题,抗CD20单克隆抗体,(B-cell marker),减少B-cell 的数量和抗体水平,作为 CHOP-R,EPOCH-R方案的一部分，常被使用,增加HBV再激活的风险，包括 HBsAg（-）的病人,逆转学清转换,:,由于免疫控制的丧失，原先HBsAg阴性的病人可以再次出现HBsAg阳性,Yeo W,et al.Hepatology.2006;43:209-220.Papamichalis P,et al.Clin Res Hepatol Gastroenterol.2012;36:84-93.,Rituximab:一特殊的问题抗CD20单克隆抗体(B,采用Rituximab治疗的 HBsAg（-）患者的HBV再激活,Patients with diffuse large B-cell lymphoma,HBsAg-negative,anti-HBcpositive individuals treated with CHOP or CHOP-R,HBV Reverse,Seroconversion,HBV-Related,Death,Yeo W,et al.J Clin Oncol.2009;27:605-611.,Risk of reactivation with rituximab significant in anti-HBc positive,40,30,20,10,0,24,0,0,5,Proportion of Anti-HBc Positive,HBsAg-Negative Patients(%),CHOP(n=25),CHOP-R(n=21),采用Rituximab治疗的 HBsAg（-）患者的HBV再,与,Rituximab 相关的HBV 再激活:典型的迟发且严重,逆转HBV血清转换,1,Among 5 patients who reactivated,1 during fifth cycle of chemotherapy;3 median of 98 days AFTER last rituximab cycle;can occur early as well,Median peak ALT:809 U/L(362-3499),Median peak bilirubin:65 mol/L(19-249),已报道的其他情况,Including instances of liver failure and liver-related deaths,Yeo W,et al.J Clin Oncol.2009;27:605-611.,Risk Factors for reactivation,Men women(almost all cases),Anti-HBs negative(or low titer),?increased age(50 yrs),与Rituximab 相关的HBV 再激活:典型的迟发且严,接受Rituximab治疗的抗HBc阳性患者的处理,无共识且资料有限,选择,化疗前开始抗病毒治疗,化疗后密切监测HBVDNA，若出现阳性即开始抗病毒治疗,化疗后密切监测HBsAg，若出现阳性即开始抗病毒治疗,化疗后密切监测HBsAg 和HBVDNA，若出现阳性即开始抗病毒治疗,接受Rituximab治疗的抗HBc阳性患者的处理无共识且资,骨髓抑制增加再激活的风险,再激活几率显著升高,(HBsAg positive),Up to 54%,1,need preemptive antiviral therapy!,Long-term complications:cirrhosis in 10%,2,如果仅抗HBc阳性者，血清转换被逆转现象常见,【3】,Up to 50%become HBsAg positive,use preemptive antivirals,May occur very late,捐献者的HBV状态非常重要,1,4,If natural immunity(anti-HBs,anti-HBc):may clear HBsAg,If vaccinated(anti-HBs):possibly some protection,1.Lau GK,et al.Bone Marrow Transplant.1997;19:795-799.2.,Hui CK,et al.Blood.2005;106:464-469.,3.Onozawa M,et al.Transplantation.2005;79:616-619.4.Lau GK,et al.J Infect Dis.1998;178:1585-1591.,骨髓抑制增加再激活的风险再激活几率显著升高(HBsAg p,类固醇增加HBV再激活发生的风险,50 patients with NHL who were HBsAg positive randomized to epirubicin,cyclophosphamide and etoposide(ACE),prednisolone(P),Cheng AL,et al.Hepatology.2003;37:1320-1328.,HBV,Reactivation,Jaundice,Survival,at 4 Yrs,ALT,10 x ULN,Complete,Remission,*,*,P,.05,Prednisolone increased risk and severity of HBV reactivation,but trend toward improved NHL outcome,HBsAg Patients(%),100,80,60,40,20,0,38,73*,13,44*,4,28*,35,46,36,68,ACE,PACE,类固醇增加HBV再激活发生的风险50 patients wi,HBV再激活的治疗和预防,HBV再激活的治疗和预防,Watch for withdrawal flares,采用化疗/免疫调节剂治疗患者的管理,HBsAg+,HBsAg-,anti-HBc+,HBV DNA,HBV DNA,LAM x 6-12 mos,posttherapy,ETV/TDF until HBV endpoints,Positive,Positive,Negative,Test HBsAg q mo,HBV DNA q 3 mos,Until 6-12 mos posttherapy,*Caveats:,If concern about monitoring,err on side of treatment,High risk:anti-HBs negative older men consider up-front treatment,1.5 x ULN,Preemptive group:start LAM on Day 1 of CHOP,Preemptive antivirals decrease HBV reactivation,HBV Reactivation and Hepatitis Flare,HBV Reactivationand Jaundice,HBV Reactivation and ALT 10 x ULN,Death,(After ChemoTx),100,80,60,40,20,0,HBsAg Patients(%),48,8,36,0,20,0,0,8,预先抗病毒治疗的价值HBsAg-positive patie,如何选择抗病毒治疗方案与监测,治疗方案的选择受,HBV DNA 水平的影响,HBV DNA 2000 IU/mL:entecavir or tenofovir,治疗方案的选择受治疗时间长短的影响,12 mos:entecavir or tenofovir,HBV DNA and ALT 应该每3个月检测一次,EASL.J Hepatol.2009;50:227-242.Lok AS,et al.Hepatology.2009;50:661-662.,如何选择抗病毒治疗方案与监测治疗方案的选择受 HBV DNA,抗病毒治疗的时间,什么时间开始,Ideally before or together with chemotherapy,Do not delay start of chemotherapy,什么时间停止,If baseline HBV DNA 2000 IU/mL:high risk of withdrawal flare,Continue therapy as for chronic HBV infection,If baseline HBV DNA 2000 IU/mL,6-12 mos after end of chemotherapy,每月检测HBVDNA和ALT监测停药后肝炎是否复发,EASL.J Hepatol.2009;50:227-242.Lok AS,et al.Hepatology.2009;50:661-6
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