Transfusion-Transmitted Hepatitis E Virus Infection in France

There is growing concern regarding the risk of transfusion- transmitted (TT) hepatitis E. Since the first described case in 2006, several TT hepatitis E have been reported to the French hemovigilance network. We performed a retrospective analysis of all cases of TT hepatitis E reported between 2006 and 2016. Transfusion-transmitted hepatitis E with high imputability according to phylogenetic analysis occurred in 23 patients aged 8 to 88 years and involved mostly solid organ recipients (n = 9) or patients with malignant hematological diseases (n = 9, including 4 hematopoietic allograft recipients). Involved blood products were plasma (n = 7), among which 6 had undergone pathogen reduction with solvent/detergent (n = 4) or amotosalen + ultra-violet A (UVA) (n = 2 from 1 donation) treatments, red blood concentrates (n = 7), apheresis platelets concentrates (n = 3) and whole blood pooled platelets concentrates (n = 6), among which one had underwent amotosalen + UVA treatment. Median hepatitis E virus (HEV) RNA dose infused was 5.79 [4.36–10.10] log IU. HEV infection progressed to chronic hepatitis E in 14 (61%) immunocompromised patients, 2 of whom had advanced liver fibrosis at diagnosis. Chronic hepatitis E patients cleared HEV with ribavirin treatment (n = 10), after immunosuppressive drug reduction (n = 3), or spontaneously (n = 1). One additional organ transplant recipient with associated co-morbidities died with ongoing HEV infection and multiple organ failure. The other 8 (34.8%) patients with TT hepatitis E cleared HEV within 6 months with ribavirin treatment (n = 3), reduced immunosuppression (n = 1) or spontaneously (n = 4). Red cells, platelets, and plasma transfusions may be associated with TT hepatitis E that can evolve to chronic hepatitis E in immunocompromised patients. Hepatitis E virus has emerged in France as a clinically significant TT infection risk.     

甲型肝炎病毒合并戊型肝炎病毒感染136例临床分析

目的　观察分析甲型病毒性肝炎合并戊型病毒性肝炎 (甲肝合并戊肝 )的临床表现及转归预后。方法　采用ELISA方法检测患者抗HAV IgM和抗HEV。结果　甲肝合并戊肝出现发热和肝大的病例分别占 6 9.85 %和 6 3 .97% ,显著高于单纯甲型病毒性肝炎 (甲肝 )的 3 7.0 0 %和 3 5 .43 %。甲肝合并戊肝发病的平均年龄为 3 1.42± 11.2 1岁 ,显著高于甲肝的 2 3 .2 1± 9.2 3岁。结论　甲肝合并戊肝也是与甲肝类似的自限性、急性、黄疸型肝炎 ,但甲肝合并戊肝具有发病以中青年为主 ,发病年龄较甲肝偏大、发热和肝大发生率高、黄疸时间较长的特点。     

戊型肝炎病毒不同生物标志物的关联和基因分型

目的 分析戊型肝炎病毒不同生物标志物的相关性及其基因型和流行病学特点.方法 收集2007～2009年安庆市立医院临床检测为急性散发性肝炎患者的系列血清,采用酶联免疫(enzyme-linked immunosorbent assay,ELISA)试剂检测HEV-IgG抗体、HEV-IgM抗体,采用巢氏逆转录聚合酶链式反...     

应用蛋白芯片技术筛选戊型肝炎病毒优势表位抗原

目的筛选戊型肝炎病毒优势表位抗原以便研发新型戊型肝炎诊断试剂。方法通过计算机辅助软件分析,利用改构的高效表达载体表达了HEV1型与HEV4型ORF2和OBF3的17种表位抗原,利用蛋白芯片技术平台筛选优势表位抗原。结果在所获得的17种表位抗原中筛选到4种可以作为研发新型戊型肝炎诊断试剂候选抗原的优势表位抗原。结论利用蛋白芯片技术快速准确地筛选到4种可用于研发新型戊型肝炎诊断试剂的候选优势表位抗原。     

Hepatitis B Virus

Candidia spp. are responsible for contributing to the increasing global prevalence of fungal infections. Fluconazole (Diflucan^®, Pfizer) is a triazole that has established an exceptional therapeutic record for candida infections including oropharyngeal and esophageal candidiasis, vulvovaginal candidiasis, candidemia and disseminated candidiasis. It is both an oral and parenteral fungistatic agent that inhibits ergosterol synthesis in yeasts. Extensive clinical studies have demonstrated fluconazole’s remarkable efficacy, favorable pharmacokinetics and reassuring safety profile, all of which have contributed to its widespread use. Fluconazole became the first antifungal with worldwide sales exceeding billions of dollars, therefore providing an incentive for the pharmaceutical industry to develop new antifungals. This review will examine the contributions and limitations of fluconazole in the treatment of superficial and invasive candidiasis syndromes.     

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.     

Hepatitis E

Hepatitis E is an important public health disease in developing countries where sanitary conditions are not well established. In developed countries, it is sporadic and mainly "imported". The causative agent of hepatitis E, hepatitis E virus (HEV), is a single-stranded positive-sense RNA virus, that belongs to the genus Hepevirus in the family Hepeviridae. Recent development of specific HEV RNA and HEV antibody detection revealed cases of indigenous HEV infection. Many cases are associated with uptake of raw meat of HEV-infected animals. Although the natural life cycle of HEV is not known, new aspects of HEV infection, zoonosis, is emerged.     

Antiviral Activities of Different Interferon Types and Subtypes against Hepatitis E Virus Replication

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients, and type I interferon (IFN) has been evaluated in a few infected transplant patients in vivo. In this study, the antiviral effects of different exogenously administered interferons were investigated by using state-of-the-art subgenomic replicon and full-length HEV genome cell culture models. Hepatitis C virus (HCV) subgenomic replicons based on the genotype 2a JFH1 isolate served as the reference. The experiments revealed that HEV RNA replication was inhibited by the application of all types of IFN, including IFN-α (type I), IFN-γ (type II), and IFN-λ3 (type III), but to a far lesser extent than HCV replication. Simultaneous determination of interferon-stimulated gene (ISG) expression levels for all IFN types demonstrated efficient downregulation by HEV. Furthermore, different IFN-α subtypes were also able to block viral replication in combination with ribavirin. The IFN-α subtypes 2a and 2b exerted the strongest antiviral activity against HEV. In conclusion, these data demonstrate for the first time moderate anti-HEV activities of types II and III IFNs and different IFN-α subtypes. As HEV employed a potent anti-interferon mechanism by restricting ISG expression, exogenous application of IFNs as immunotherapy should be carefully assessed.     

丙型肝炎病毒包膜蛋白基因片段的克隆与表达

应用ＲＴ－ＰＣＲ和基因重组技术，从湖南地区丙型肝炎病毒（ＨＣＶ）感染者血清中克隆了ＨＣＶ包膜蛋白基因片段（Ｅ１，Ｅ２／ＮＳ１），经与已知基因型的ＨＣＶ－１，ＨＣＶ－Ｊ，ＨＣＶ－Ｊ６和ＨＣＶ－Ｊ８进行核苷酸序列的比较分析，这些基因片段属１ｂ型ＨＣＶ基因。将克隆基因重组于表达质粒ＰＭＡＬ－ＣＲＩ中，在大肠杆菌内进行高效表达，获得了融合蛋白ＭＢＰ－Ｅ１，ＭＢＰ－Ｅ２／ＮＳ１，经ＷｅｓｔｅｒｎＢｌｏｔ分析证实这些融合蛋白具有ＨＣＶ的特异抗原活性，提示这些融合蛋白可用于ＨＣＶ感染的临床诊断和发病机理的研究。     

乙型肝炎病毒与丙型肝炎病毒重叠感染的探讨

乙型肝炎和丙型肝炎是对人类健康危害甚大的肝炎中的两大类，乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）均可由输血，静脉和母婴垂直传播等多种途径感染人类。乙型肝炎在我国属高发区，乙型肝炎病毒感染是我国原发性肝细胞癌发生的主要原因，而乙型肝炎病毒和丙型肝炎病毒的重叠感染对肝病的慢性化，严重化，癌变起着不可忽视的作用。作者对60例HBV感染者中重叠HCV感染的检测，将有助于临床诊断和治疗。