Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and d...Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.展开更多
目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV ...目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV DNA。结果HBV感染者外周血CD4+T细胞百分率及CD4+/CD8+比值较正常对照组明显减低(36.8±10.6%vs 39.4±9.8%,P<0.05;1.5±0.8 vs 1.9±0.9,P<0.01),CD8+T细胞百分率明显升高(27.9±8.3%vs 24.1±7.0%,P<0.01),而CD3+T细胞百分率无明显差异(70.2±10.3%vs 69.9±5.2%,P>0.05)。根据HBV感染者血清中HVB DVA载量的高低,将它们分为低拷贝组(103-104copies/ml),高拷贝组(105-108copies/ml)以及DNA阴性组(<102copies/ml)。低拷贝组和高拷贝组的CD4+T细胞百分率及CD4+/CD8+比值比对照组明显减低(36.4±10.9%vs 39.4±9.8%,P<0.05;36.4±10.9%vs 39.4±9.8P<0.05;1.5±0.9 vs 1.9±0.9,P<0.01;1.1±0.7 vs 1.9±0.9,P<0.01),高拷贝组的CD4+/CD8+比值比低拷贝组和DNA阴性组明显减低(1.1±0.7 vs 1.5±0.9,P<0.01;1.1±0.7 vs 1.6±0.8,P<0.01),CD8+细胞百分率明显高于对照组和DNA阴性组(29.4±8.4%vs 24.1±7.0%,P<0.01;29.4±8.4%vs 25.7±7.3%vs 24.1±7.0%P<0.05)。而CD3+T细胞百分率在各组之间没有明显差异存在(P>0.05),CD4+在低、高拷贝组及DNA阴性组之间虽无明显差异存在(P>0.05),但随着DNA复制的增加,CD4+呈逐渐减少趋势。结论HBV感染可导致感染者细胞免疫功能的改变,HBA DNA复制增加进一步加重乙肝病毒感染者T细胞亚群的率乱,CD4+/CD8+比值的动态变化可及时提示临床HBV感染者细胞免疫功能的变化并加强临床的临测。展开更多
文摘Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.
文摘目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV DNA。结果HBV感染者外周血CD4+T细胞百分率及CD4+/CD8+比值较正常对照组明显减低(36.8±10.6%vs 39.4±9.8%,P<0.05;1.5±0.8 vs 1.9±0.9,P<0.01),CD8+T细胞百分率明显升高(27.9±8.3%vs 24.1±7.0%,P<0.01),而CD3+T细胞百分率无明显差异(70.2±10.3%vs 69.9±5.2%,P>0.05)。根据HBV感染者血清中HVB DVA载量的高低,将它们分为低拷贝组(103-104copies/ml),高拷贝组(105-108copies/ml)以及DNA阴性组(<102copies/ml)。低拷贝组和高拷贝组的CD4+T细胞百分率及CD4+/CD8+比值比对照组明显减低(36.4±10.9%vs 39.4±9.8%,P<0.05;36.4±10.9%vs 39.4±9.8P<0.05;1.5±0.9 vs 1.9±0.9,P<0.01;1.1±0.7 vs 1.9±0.9,P<0.01),高拷贝组的CD4+/CD8+比值比低拷贝组和DNA阴性组明显减低(1.1±0.7 vs 1.5±0.9,P<0.01;1.1±0.7 vs 1.6±0.8,P<0.01),CD8+细胞百分率明显高于对照组和DNA阴性组(29.4±8.4%vs 24.1±7.0%,P<0.01;29.4±8.4%vs 25.7±7.3%vs 24.1±7.0%P<0.05)。而CD3+T细胞百分率在各组之间没有明显差异存在(P>0.05),CD4+在低、高拷贝组及DNA阴性组之间虽无明显差异存在(P>0.05),但随着DNA复制的增加,CD4+呈逐渐减少趋势。结论HBV感染可导致感染者细胞免疫功能的改变,HBA DNA复制增加进一步加重乙肝病毒感染者T细胞亚群的率乱,CD4+/CD8+比值的动态变化可及时提示临床HBV感染者细胞免疫功能的变化并加强临床的临测。
