A new approach for therapeutic vaccination against chronic HBV infections

There are currently about 257 million people suffering from chronic HBV infection worldwide. In many cases, an insufficient T cell response is causative for establishment of a chronic infection. To ensure a robust cellular immune response and induction of neutralizing antibodies a novel vaccine platform based on modified cell–permeable HBV capsids was utilized. Cell permeability was achieved by fusion of the membrane–permeable TLM-peptide to HBV core monomers, assembling the capsids. Insertion of a Strep-tagIII into the spike tip domain that protrudes from the capsid surface enables flexible loading with antigens that are fused to streptavidin. In this study, HBV surface antigen-derived PreS1PreS2 domain, fused to monomeric streptavidin, served as cargo antigen. Binding between antigen and capsids was characterized by surface plasmon resonance spectroscopy, electron microscopy and density gradient centrifugation. Confocal immunofluorescence microscopy and in vivo imaging of immunized mice demonstrated membrane permeability of cargo-loaded carriers and spread of antigen over the whole organism. Immunization experiments of mice revealed a robust induction of a specific cellular immune response, leading to destruction of HBV-positive cells and induction of HBV-specific neutralizing antibodies. Membrane permeability of these carriers allows needle-free application of antigen-loaded capsids as evidenced by induction of an HBV-specific CTL response and HBV-specific B cell response after oral or transdermal vaccination.These data indicate that cell–permeable antigen carriers, based on HBV capsids and loaded with HBV antigen, have the capacity to induce a cellular and a neutralizing humoral immune response. In addition, cell permeability of the vaccine platform enables antigen transfer across several cell layers, that could allow oral or transdermal immunization.     

HBeAg阳性慢性乙型肝炎患者HBV前C/BCP突变/准种与HBeAg和HBV DNA的关系

目的探讨HBeAg阳性慢性乙型肝炎（eP-CHB）HBV前C/BCP突变/准种及其与HBeAg、HBV DNA水平的关系。 方法采用断面研究对2016年1月至2018年12月就诊于首都医科大学附属北京佑安医院的220例eP-CHB患者进行前C/BCP突变检测，其中24例患者进行前C/BCP区扩增、克隆，同步检测血清HBeAg和HBV DNA水平，分析前C/BCP突变/准种的发生情况及其与HBeAg和HBV DNA水平的关系。 结果220例eP-CHB患者中，HBV前C/BCP总突变率为70.0%（154/220），前C/BCP共同突变率为18.2%（40/220），前C突变率为30.9%（68/220），BCP突变率为57.3%（126/220）。HBV DNA≥ 5 lgIU/ml患者上述4种突变检出率均高于HBV DNA< 5 lgIU/ml者，其中前C/BCP总突变和BCP突变患者差异有统计学意义（χ² = 5.809、P = 0.016，χ² = 5.081、P = 0.024）。HBeAg水平越低（< 500 COI、500～1 000 COI和> 1 000 COI共3组患者比较），以上4种突变检出率越高，差异有统计学意义（χ² = 31.738、17.291、16.263、22.164，P均< 0.001）。HBV DNA≥ 5 lgIU/ml患者中，HBeAg水平越低，以上4种突变检出率越高，差异亦均有统计学意义（χ² = 40.503、19.654、16.727、29.119，P < 0.001）。准种检测中，前C区高突变组患者HBeAg水平低于低突变组，差异有统计学意义（t = 2.230、P = 0.017），前C、BCP高突变组与低突变组间HBV DNA水平差异无统计学意义（t = 0.624、P = 0.462，t = 0.893、P = 0.317）。 结论eP-CHB患者中仍存在广泛的前C/BCP突变。高HBV DNA、低HBeAg表达者，前C和BCP突变的发生率较高；前C区突变株在准种中比率高者更影响HBeAg的表达。推测前C/BCP突变可能是eP-CHB出现低HBeAg、高HBV DNA，并导致抗病毒治疗停药后易复发的原因。     

宁夏地区朝觐人员HBV感染者基因分型研究

目的了解宁夏地区朝觐人员乙型肝炎基因分布特点,为探讨宁夏地区朝觐人员乙肝流行趋势提供科学依据。方法采用ELISA法对宁夏地区2010至2012后采用荧光PCR检测方法,对乙肝病毒感染者进行基因分型。结果 90例乙型肝炎HBs Ag阳性者HBV DNA经荧光PCR方法分型,B型5例(5.56%),C型82例(91.11%),其他型3例(3.33%),经统计学分析不同基因型分布有统计学意义;HBV DNA基因型在性别中分布无差异,因此,认为性别与乙肝基因型不具有相关性。结论宁夏地区朝觐人员乙型肝炎患者HBV基因型分布基本符合我国北方的分布特点,以C型为主。     

慢性HBV感染者HBsAg血清学清除后为什么还发生肝细胞癌?

本文综述了慢性HBV感染者HBsAg血清学清除后发生肝细胞癌的风险、机制及启示。     

乙肝孕妇血清标志物模式与HBV-DNA载量及肝功能关系研究

目的探讨乙肝孕妇血清标志物模式、HBV-DNA载量及肝功能三者之间的关系,为孕期乙肝病毒感染情况的监控和乙肝病毒母婴传播的预防提供参考。方法选取2019年1月-11月在我院产检的767例乙肝表面抗原阳性孕妇的乙肝血清标志物模式、肝功能指标的丙氨酸氨基转移酶(alamine aminotransferase,ALT)及HBVDNA载量进行研究,探讨三者间的关系。结果HBsAg、HBeAg、HBcAb阳性组孕妇HBV-DNA阳性率及病毒载量均高于其余两组(P<0.05);ALT升高程度与HBV-DNA载量具有一定相关性(r=0.255,χ^2=80.150,P=0.000);HBeAg阳性组和HBeAg阴性组间HBV-DNA阳性率、ALT异常率差异均有统计学意义。结论HBV-M、HBV-DNA与肝功能之间有一定的相关性,大三阳孕妇中高病毒载量比例高,应加强乙肝孕妇孕期各项指标的监测,必要时进行干预治疗。     

Risk-stratified management strategies for HBV reactivation in RA patients receiving biological and targeted therapy: A narrative review

It is estimated that more than two billion people around the world have been infected by Hepatitis B virus (HBV). Reactivation of HBV (rHBV) is a potentially fatal complication after biological therapy. With the increasing use of biologics and targeted therapy in rheumatoid arthritis (RA) patients who are refractory to conventional synthetic disease-modifying anti-rheumatic drugs, rHBV in those with past infection has become increasingly problematic, especially in HBV-endemic regions. Among those receiving biological therapy, the risk of rHBV varies according to the status of HBV infection and the degree of biologic-related immunosuppression. As rHBV is largely preventable, it is imperative that the risk status of rHBV in RA patients receiving biological and targeted therapy be stratified. Therefore, the aim of this review was to summarize the reported data on rHBV, and propose management strategies for RA patients with different risks of rHBV based on evidence presented in the current literature.     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.