Previous hepatitis E virus infection,cirrhosis and insulin resistance in patients with chronic hepatitis C

Background

Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance.

Chronic hepatitis E: A brief review

Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.     

河南省人民医院门诊患者戊型病毒性肝炎的阳性率调查

目的 通过检测部分门诊病例血清的戊型肝炎病毒标志物（HEV IgG）,简要描述本地区的戊型病毒性肝炎的感染水平.方法 收集河南省人民医院内科门诊病例血清415份,应用万泰公司的戊型病毒性肝炎诊断试剂盒进行ELISA检测,检测结果进行统计学分析,对不同分组进行x2检验.结果 415例门诊病例的HEV阳性率为21.93％,在性别间、年龄分组间,差异有统计学意义,而在城乡间的差别无统计学意义.结论 我市的戊型病毒性肝炎阳性率处于全国HEV感染率的平均水平,成人的HEV阳性率显著性高于青少年.在低年龄阶段进行有效的疫苗接种,可以控制戊型病毒性肝炎在我省的流行.     

A novel linear neutralizing epitope of hepatitis E virus

Hepatitis E virus (HEV) is a serious public health problem that causes acute hepatitis in humans and is primarily transmitted through fecal and oral routes. The major anti-HEV antibody responses are against conformational epitopes located in a.a. 459–606 of HEV pORF2. All reported neutralization epitopes are present on the dimer domain constructed by this peptide. While looking for a neutralizing monoclonal antibody (MAb)-recognized linear epitope, we found a novel neutralizing linear epitope (L2) located in a.a. 423–437 of pORF2. Moreover, epitope L2 is proved non-immunodominant in the HEV-infection process. Using the hepatitis B virus core protein (HBc) as a carrier to display this novel linear epitope, we show herein that this epitope could induce a neutralizing antibody response against HEV in mice and could protect rhesus monkeys from HEV infection. Collectively, our results showed a novel non-immunodominant linear neutralizing epitope of hepatitis E virus, which provided additional insight of HEV vaccine.     

戊型肝炎病毒与鼠形动物的关系

戊型肝炎病毒所导致的戊型病毒性肝炎（戊型肝炎）全球流行严重,是重要的公共卫生问题之一。戊型肝炎病毒是一种动物源性单股正链RNA病毒,属于戊型肝炎病毒科,该科分为正戊肝病毒属和鱼戊肝病毒属。正戊肝病毒属包括A物种、B物种、C物种、D 物种共4种;鱼戊肝病毒属仅有A物种。先前的研究认为戊型肝炎病毒不会跨物种传播,但最近发现有戊肝病毒通过鼠形动物传染给人的情况,而鼠形动物在病毒传播及流行过程中扮演的角色和发挥的作用尚不清楚。本文综述了A物种正戊肝病毒和C物种正戊肝病毒与鼠形动物的关系,并对香港鼠传人戊肝事件进行思考,推测此次传播可能存在病毒变异,使病毒的传染力增强,获得了跨物种传播的能力;C物种正戊肝病毒所致的戊肝可能成为一种新的人兽共患病。建议对鼠形动物感染戊肝病毒的类型、感染率及空间分布特征进行深入研究,前移戊肝防控关口,为科学精准防控戊型肝炎提供新的思路。同时,鼠形动物是动物源性疾病病原体的重要宿主,明确该种群携带戊肝病毒的情况,有助于科学评估戊肝病毒通过鼠形动物传染给人的潜在风险。     

Seroprevalence of hepatitis E antibodies in a population of recyclable waste pickers in Brazil

BackgroundHepatitis E virus (HEV) infection represents an important cause of acute viral hepatitis. Selective waste collection is a widespread activity carried out by the urban poor, and recyclable waste pickers have a lifestyle that makes this group highly vulnerable to unfavorable socio-economic and environmental factors. To date, the epidemiology of HEV infection in this population remains unknown.ObjectivesTo assess the seroprevalence of hepatitis E-specific antibodies in a population of recyclable waste pickers in Brazil.Study designBetween April 2010 and May 2011, a cross-sectional study was conducted among recyclable waste pickers from all 15 recycling cooperatives in Goiânia City, Central Brazil. The participants were tested for serological markers indicative of HEV infection.ResultsOf 432 individuals asked to participate in the survey, 431 (99.8%) agreed to participate. Twenty-four of 431 participants were anti-HEV IgG positive by ELISA. Of these, 22 were confirmed positive by immunoblot, resulting in an anti-HEV IgG prevalence of 5.1% (95% CI: 3.4–7.6). In addition, four individuals were anti-HEV IgM positive by ELISA. Of these, three (0.7%; 95% CI: 0.4–2.4) were confirmed anti-HEV IgM positive by immunoblot, but were HEV RNA negative. One was concurrently positive for anti-HEV IgG. Only age > 40 years was independently associated with the presence of anti-HEV.ConclusionsThese findings demonstrated that the prevalence of HEV antibodies among recyclable waste pickers in Central Brazil is relatively low and increased with age.     

Evaluation of antigenicity and cell mediated immunity of Hepatitis E virus patients: Using non radioactive MTT assay

Hepatitis E virus (HEV) is an important cause of hepatitis in developing nations. Disease spans from asymptomatic infection to acute viral hepatitis (AVH) and acute liver failure (ALF). Cell-mediated immunity (CMI) is less studied. Studies document CMI in HEV patients using [³H]-thymidine incorporation (radioactive in nature). The aim of this study was to evaluate the antigenicity of recombinant HEV ORF 2 peptide (452-617 a.a) (pORF2) by non-radioactive MTT assay and detecting the proliferation indices of primary PBMC culture. A total of 27 laboratory confirmed HEV patients (16 AVH and 11 ALF) and 20 apparently healthy individuals (HC) were included. PBMCs were isolated, plated and stimulated with pORF2. After an incubation of 4 days, cells were looked for blastogenic transformation and subjected to MTT assay. PI of AVH, ALF and healthy controls were found to be 3.249 ± 0.219, 1.748 ± 0.076 and 0.226 ± 0.017, respectively. PI of AVH Vs HC, ALF Vs HC and AVH Vs ALF were found to be significantly higher (P < 0.0001). This study demonstrates MTT to be an adaptable technique to evaluate CMI in HEV patients. Recombinant pORF2 was found to be antigenic in nature and PBMCs from AVH patients were immunologically more reactive than ALF patients.     

A trivalent vaccine candidate against hepatitis E virus,norovirus, and astrovirus

Hepatitis E virus (HEV), norovirus (NoV), and astrovirus (AstV) are enterically-transmitted viral pathogens causing epidemic or endemic hepatitis (HEV) and gastroenteritis (NoV and AstV) respectively in humans, leading to significant morbidity and mortality worldwide. While a recombinant subunit vaccine against HEVs is available in China, there is no commercial vaccine or antiviral against NoV or AstV. We report here our development of a trivalent vaccine against the three viral pathogens through our new polymer vaccine technology. All HEV, NoV, and AstV are non-enveloped RNA viruses covered by a protein capsid, featuring surface protruding (P) proteins that are responsible for virus–host interaction. These dimeric P proteins elicit neutralizing antibody and are good targets for subunit vaccine development. The trivalent subunit vaccine was developed by fusion of the dimeric P domains of the three viruses together that formed tetramers. This trivalent vaccine elicited significantly higher antibody responses in mice against all three P domains than those induced by a mixture of the three free P domains (mixed vaccine). Furthermore, the post-immune antisera of the trivalent vaccine showed significantly higher neutralizing titers against HEV infection in cell culture and higher blocking activity against NoV binding to HBGA ligands than those of the post-immune sera of the mixed vaccine. Thus, the trivalent vaccine is a promising vaccine candidate against HEV, NoV, and AstV.     

Real-time stability of a hepatitis E vaccine (Hecolin®) demonstrated with potency assays and multifaceted physicochemical methods

The first prophylactic vaccine against hepatitis E virus (HEV), Hecolin®, was licensed in China. Recombinant p239 virus-like particle (VLP) is its active component with dimeric protein as the basic building block harboring the immuno dominant and neutralizing epitopes. The real time and real condition stability of the prefilled syringes for the vaccine was demonstrated using both in vivo mouse potency and in vitro antigenicity assays. A total of 12 lots of Hecolin® were assessed with a set of assays after storage at 2–8 °C for 24 months. The particle characteristics of p239 VLP recovered from the aluminum-containing adjuvant was assessed with different methods including analytical ultracentrifugation, high performance size exclusion chromatography and transmission electron microscopy. The thermal and conformational stability of the adsorbed antigen was assessed using differential scanning calorimetry. The protein integrity of the recovered p239 antigen was demonstrated using SDS-PAGE with silvering staining, LC-MS and MALDI-TOF MS. Most importantly, the binding activity to the neutralizing antibody or vaccine antigenicity was measured using an epitope-specific and real-time SPR assay and a monoclonal antibody-based sandwich ELISA. Taken together, the overall good stability of the Hecolin® prefilled syringes was demonstrated with unaltered molecular and functional attributes after storage at 2–8 °C for 24 months.     

Live recombinant Lactococcuslactis expressing avian hepatitis virus ORF2 protein: Immunoprotection against homologous virus challenge in chickens

Avian hepatitis E virus (aHEV) is a pathogen associated with hepatitis-splenomegaly syndrome in chickens. To date, no commercial vaccine is available for preventing aHEV infection. In this study, three recombinant LactococcuslactisNZ9000experimental live vaccines expressing cytoplasmic, secreted, and cell wall-anchored forms of aHEV truncated ORF2 protein spanning amino acids 249–606 (ΔORF2) were constructed using pTX8048 vector and characterized. Each chicken was immunized three times at two-week intervals with one of the three live aHEV ORF2 vaccines (experimental group) or with live vaccine containing empty vector only (control group). Both groups were then challenged with aHEV and evaluated to compare immune responses and immunogenic effects. Serum IgG levels, secretory IgA (sIgA) levels in bile and jejunal lavage fluid, and mRNA expression levels ofIL-2 and IFN-γ in liver and spleen were significantly higher in experimental chickens than in controls. Meanwhile, post-challenge serum and fecal virus loads were significantly lower in experimental chickens versus controls. Moreover, on day 7 post infection (PI), serum lactose dehydrogenase (LDH) levels were significantly higher in controls than experimental chickens. Furthermore, at day 28 PI, obvious gross pathological lesions and histopathological changes typical for aHEV infection were observed in control livers and spleens, with only moderate pathological changes observed in the experimental group. The results of this study collectively demonstrate that an oral vaccineusing L.lactisNZ9000 as a delivery vector for aHEV immunogenic antigen could effectively control aHEV infection of chickens.