Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has b...Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.展开更多
目的观察慢性乙型肝炎(CHB)患者单核细胞来源树突状细胞(moDC)Toll样受体(TLR)的表达,并分析抗病毒相关TLR(TLR3、TLR4、TLR7、TLR8、TLR9)在CHB患者moDC的表达特征及意义。方法用羟乙基淀粉(HES)分离10例CHB患者及15例健康对照外周血...目的观察慢性乙型肝炎(CHB)患者单核细胞来源树突状细胞(moDC)Toll样受体(TLR)的表达,并分析抗病毒相关TLR(TLR3、TLR4、TLR7、TLR8、TLR9)在CHB患者moDC的表达特征及意义。方法用羟乙基淀粉(HES)分离10例CHB患者及15例健康对照外周血单个核细胞(PBMC),经重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)、重组人白细胞介素4(rhlL-4)诱导培养树突状细胞(DC),经流式细胞仪用特异性单克隆抗体检测不同成熟阶段DC的TLR表达,并以HBcAg负载未成熟DC,应用FACS分析HBcAg的负载效率及细胞内IFN-γ、IL-4表达水平。结果moDC不同成熟阶段TLR的表达水平不同;CHB患者的未成熟moDC(imDC)表达的TLR7、TLR8低于健康对照(75.9%、1.0%比98.4%、15.4%,P<0.05),CHB患者成熟moDC(mDC)表达TLR3、TLR7低于健康对照(9.5%、79.7%比11.5%、90.7%,P<0.05);应用HBcAg分别于细胞培养第3天和第5天冲击DC,第1次冲击后48 h HBcAg的膜内、膜外负载率分别为53.0%和7.5%,第2次冲击后分别为80.2%和19.0%;HBcAg负载或未负载的moDC,均刺激淋巴细胞高表达IFN-γ,较少表达或不表达IL-4,呈现显著的Th1免疫应答。结论CHB患者moDe的抗病毒相关TLR表达低下,且可能是其DC功能低下的重要原因之一;应用HBcAg冲击imDC,可使其有效负载HBcAg,负载后DC的成熟过程及功能不受影响,仍以诱导Th1免疫应答反应为主。展开更多
文摘Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.
文摘目的观察慢性乙型肝炎(CHB)患者单核细胞来源树突状细胞(moDC)Toll样受体(TLR)的表达,并分析抗病毒相关TLR(TLR3、TLR4、TLR7、TLR8、TLR9)在CHB患者moDC的表达特征及意义。方法用羟乙基淀粉(HES)分离10例CHB患者及15例健康对照外周血单个核细胞(PBMC),经重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)、重组人白细胞介素4(rhlL-4)诱导培养树突状细胞(DC),经流式细胞仪用特异性单克隆抗体检测不同成熟阶段DC的TLR表达,并以HBcAg负载未成熟DC,应用FACS分析HBcAg的负载效率及细胞内IFN-γ、IL-4表达水平。结果moDC不同成熟阶段TLR的表达水平不同;CHB患者的未成熟moDC(imDC)表达的TLR7、TLR8低于健康对照(75.9%、1.0%比98.4%、15.4%,P<0.05),CHB患者成熟moDC(mDC)表达TLR3、TLR7低于健康对照(9.5%、79.7%比11.5%、90.7%,P<0.05);应用HBcAg分别于细胞培养第3天和第5天冲击DC,第1次冲击后48 h HBcAg的膜内、膜外负载率分别为53.0%和7.5%,第2次冲击后分别为80.2%和19.0%;HBcAg负载或未负载的moDC,均刺激淋巴细胞高表达IFN-γ,较少表达或不表达IL-4,呈现显著的Th1免疫应答。结论CHB患者moDe的抗病毒相关TLR表达低下,且可能是其DC功能低下的重要原因之一;应用HBcAg冲击imDC,可使其有效负载HBcAg,负载后DC的成熟过程及功能不受影响,仍以诱导Th1免疫应答反应为主。