Lack of evidence of acute HEV infections as a sexually transmitted disease: Data from a German cohort of PrEP users

Abstract Background While the sexual transmissibility of HAV in MSM has been extensively described, the potential for sexual transmission of HEV has not been definitively established. Although HEV has been detected in the ejaculate of chronically infected men, studies among MSM PrEP users in France did not observe an elevated anti-HEV seroprevalence as an indicator of increased exposure risk by sexual intercourse. Patients and methods A total of 111 unselected PrEP users and 111 age- and sex-matched blood donors were tested for anti-HEV IgG, IgM and HEV (PCR). Of the participants 79/111 (71 %) responded to a questionnaire covering topics as sexual preferences, previous sexually transmitted diseases, profession, food consumption, and pet ownership. Results The anti-HEV IgG seroprevalence in PrEP users (22 %) did not differ significantly from the rate in controls (17 %). While one PrEP user and three controls tested positive for anti-HEV IgM, all PrEP users and controls tested PCR negative. Conclusion In immunocompetent individuals with frequent changes of sexual partners, the epidemiology of Hepatitis E Virus does not significantly involve the sexual transmission route.

Prevalence of HEV infection markers in Chinese blood donors: a meta-analysis / 中国输血杂志

【Objective】 To analyze the serological markers and RNA prevalence of HEV infection in Chinese voluntary blood donors in different regions of China, so as to provide basis for the necessity of HEV screening and the formulation of screening strategies for voluntary blood donors. 【Methods】 Databases such as CNKI, Wanfang medicine and PubMed were searched for eligible literature, and the literature data meeting the inclusion criteria were extracted for meta-analysis using R4.1.3 software. 【Results】 A total of 26 studies were included, involving 97 928, 117 831 and 82 673 cases, respectively, for anti-HEV IgG, anti-HEV IgM and HEV RNA. The pooled estimated prevalence of anti-HEV IgG, anti-HEV IgM and HEV RNA among Chinese voluntary blood donors was 23.0% [95% CI (18%, 29%)] vs 1.13% [95% CI (0.94%, 1.36%)] vs 0.028%[95%CI(0.006%, 0.059%)], and there were significant differences among different cities and regions. 【Conclusion】 The past infection rate of HEV among voluntary blood donors in China was somewhat high and with significant regional differences. The current infection rate was relatively low and had decreased compared with that in the past decade, but there was still residual risk of blood transfusion. It is necessary to pay more attention to blood HEV screening of voluntary blood donors.

HPV B19, HAV and HEV infection among voluntary blood donors in Nantong / 中国输血杂志

【Objective】 To evaluate the viability of nucleic acid test(NAT) of human parvovirus B19 (HPV B19), hepatitis A virus (HAV) and hepatitis E virus (HEV) along with routine NAT for voluntary blood donors, and to analyze HPV B19, HAV and HEV prevalence in Nantong, so as to provide reference for rational blood screening programs. 【Methods】 HPV B19 DNA, HAV RNA and HEV RNA of blood donors in Nantong from November 2021 to May 2022 were detected using NAT, and serological antibody testing was performed on NAT reactive samples. 【Results】 Three HPV B19 DNA was yielded out of 3 440 blood donors, with a positive rate of 0.09%, among which 2 were negative for HPV B19-IgM and 1 was undetermined due to insufficient sample size. HAV RNA and HEV RNA were not detected in 3 440 blood donors. HPV B19, HAV, and HEV NAT were conducted simultaneously with routine HBV, HCV and HIV screening, prolonging the test reports by 20 minutes. 【Conclusion】 Although the HPV B19 DNA, HAV RNA and HEV RNA prevalence among voluntary blood donors in Nantong is low, the risk of transfusion transmitted infection still exsits and can be reduced by NAT.

Haematological diseases associated with Hepatitis E virus infection / 临床肝胆病杂志

‍Hepatitis E virus （HEV） infection can cause acute， fulminant， and chronic hepatitis and is thus a worldwide health problem. The general population has no obvious symptoms or only mild symptoms after HEV infection， and most symptoms are self-limited and are easily ignored in clinical diagnosis. Previous reports have shown that HEV infection can cause dysfunction in multiple systems， especially the blood system， in which it often leads to a series of adverse outcomes. Comprehensive evaluation， early diagnosis， and early intervention of these HEV-related diseases will greatly reduce the medical burden of individuals and society. With reference to the previous reports， this article reviews the blood system diseases associated with HEV infection.

Research advances in the interspecies transmission of hepatitis E virus / 临床肝胆病杂志

‍Hepatitis E virus （HEV） is a pathogen for viral hepatitis and can be transmitted across species via animals. The incidence rate of hepatitis E caused by HEV infection ranks first among acute viral hepatitis worldwide， and now it has become a major public health issue that threatens human health. In recent years， more and more species have been identified as the natural hosts of HEV， and there are more routes for the interspecies transmission of HEV， which greatly inhibits the prevention and control of this virus. Therefore， this article reviews and discusses the advances in the interspecies transmission of HEV， so as to provide a reference for the prevention and control of HEV.

The mechanism of the severe exacerbation and chronicity of hepatitis E virus infection / 临床肝胆病杂志

‍Hepatitis E virus （HEV） infection is the most common cause of acute viral hepatitis worldwide， and over the past ten years， studies have shown that HEV can not only cause acute self-limiting hepatitis， but also lead to severe and chronic infection. Pregnant women or patients with underlying liver disease may progress to liver failure after HEV infection， resulting in a relatively high mortality rate， and patients receiving solid organ transplantation may progress to chronic hepatitis after HFV infection. This article introduces the diagnosis， clinical features， transmission， prevention， and treatment of severe and chronic HEV infection， discusses the features of immune response， inflammatory response， and the virus itself during the severe exacerbation and chronicity of HEV infection， and summarizes the mechanism in promoting the progression of HEV. Nevertheless， there are still large gaps between current studies and clinical application， and there is still a lack of effective diagnosis and treatment regimens for severe and chronic HEV infection. It is necessary for clinical researchers to conduct research on the pathogenesis of hepatitis E and systematic cohort studies and improve the level of clinical nursing， thereby achieving the goal of preventing hepatitis E and improving the prognosis of patients with hepatitis E.

Advances in the prevention and treatment of the high-risk population for hepatitis E / 临床肝胆病杂志

‍Hepatitis E virus （HEV） infection is one of the most common causes of acute viral hepatitis. Most patients with HEV infection are asymptomatic and the virus can be spontaneously eliminated. Pregnant women， the elderly， immunocompromised populations， patients with chronic liver disease， and individuals in close contact with HEV-infected animals are at a high risk for HEV infection. The recombinant hepatitis E vaccine HEV 239 is the only approved hepatitis E vaccine， with both short- and long-term protective efficacy. This vaccine has a favorable safety profile with few adverse events， and the high-risk populations should be given the priority to receive such vaccination. Immunocompromised individuals may develop chronic HEV infection. Ribavirin and interferon are currently the most commonly used antiviral drugs for the treatment of HEV infection； however， it still needs to develop safe and effective novel antiviral drugs for patients with contraindications to ribavirin or interferon or those who have no response to such therapy.

Hepatitis E： From behind the scenes to the front stage / 临床肝胆病杂志

‍Hepatitis E is a type of viral hepatitis caused by hepatitis E virus （HEV） infection. There are four main genotypes of HEV， namely genotypes 1‍ — ‍4. Compared with hepatitis B and hepatitis C， previous research on hepatitis E has made slow progress； however， in recent years， hepatitis E has gradually attracted more attention in China， achieving the transition from behind the scenes to the front stage. First， China has a large population base， a large number of people infected with hepatitis E， and a heavy disease burden， and thus it is necessary to attach great importance to the prevention， diagnosis， and treatment of hepatitis E. Second， the World Health Organization （WHO） has put forward the ambitious goal of eliminating viral hepatitis by 2030， and China has made remarkable achievements in the prevention and treatment of hepatitis B and hepatitis C. At present， the incidence and mortality rates of hepatitis E in China have exceeded those of hepatitis A， and the prevention and treatment of hepatitis E in China is of great significance to actively respond to the call of the WHO. Finally， Chinese researchers in the field of hepatitis E have formed Chinese Consortium for the Study of Hepatitis E， formulated related expert consensus， and established international cooperation platforms， which further promotes the research on hepatitis E in China.

Research advances in hepatitis E virus infection in pregnancy / 临床肝胆病杂志

Previous studies have shown that hepatitis E virus （HEV） infection in pregnancy can cause liver failure and adverse pregnancy outcomes such as miscarriage， stillbirth， and vertical transmission， especially in countries where HEV genotypes 1 and 2 are prevalent. In recent years， HEV infection in China is sporadic and is mainly caused by HEV genotype 4， and although studies have shown that most pregnant women with HEV infection in China have no signfinicant clinical symptoms， there is still a high incidence rate of adverse pregnancy outcomes. This article reviews the recent studies on HEV infection in pregnancy， including the advances in pathogenesis， epidemiology， prognosis， mechanism of severe exacerbation， treatment， and prognosis， and puts forward recommendations for the screening and evaluation of HEV infection in pregnancy.

Preparation of Chinese national potency reference for hepatitis E vaccine / 中国生物制品学杂志

@#ObjectiveTo prepare the hepatitis E vaccine national potency reference for the quality control of hepatitis E vaccine.MethodsA batch of hepatitis E vaccine was selected as the row material,and the screened lyoprotectant was added. After aliquot and freeze-drying,it was prepared as candidate reference material,and the homogeneity and stability were investigated,which was distributed to four laboratories for collaborative calibration and applicability study.Results The 5% trehalose + 2% dextran was selected as the lyoprotectant to prepare the candidate reference material. The aliquot accuracy of candidate reference material was 0. 7%;The coefficient of variation(CV)of antigen content homogeneity was9. 0%;The CV of aluminum content homogeneity was 4. 0%. Moisture content was 1. 7%. The candidate reference material showed good acceleration stability and reconstituted stability. A total of 18 valid data were obtained from the collaborative calibration. The results showed that the average value of median effective dose(ED50)was 0. 15 μg(95% confidence interval of 0. 12 ～ 0. 18 μg)with the intra-laboratory CV of 30. 8% ～ 64. 2%,and the inter-laboratory CV of 32. 6%. Two hepatitis E vaccines produced by two laboratories themselves and the candidate reference material showed good dose-response relationship,of which the seroconversion rate decreased with the decrease of vaccine antigen content and the curve change trend was similar.ConclusionThe first Chinese national potency reference for hepatitis E vaccine(300031-201801)was prepared,which can be used for the quality control of potency ED50detection of hepatitis E vaccine.

Prognostic value of serum carbamoyl phosphate synthase 1 in patients with hepatitis E-related acute liver failure / 中华检验医学杂志

Objective:To explore the impact of serum carbamoyl phosphate synthase 1 (CPS1) level on prognosis of patients with hepatitis E-related acute liver failure (HEV-ALF).Methods:This retrospective analysis included 100 HEV-ALF patients, 100 patients with acute hepatitis E (AHE) and 100 healthy controls who admitted or underwent health checkup from December 2018 to June 2019 in six hospitals, including the First Affiliated Hospital, Zhejiang University School of Medicine. HEV-ALF patients were divided into non-survial ( n=21) and survival ( n=79) subgroups according to results of 30-day follow-up results. HEV-ALF patients were also divided into the high ( n=50) and low ( n=50) serum CPS1 level groups. HEV-ALF patients were further divided into the improvement ( n=55), fluctuation ( n=32) and deterioration ( n=13) subgroups. The general clinical data from all participants were collected. Serum CPS1 levels were detected by enzyme linked immunosorbent assay. The survival time in the high and low serum CPS1 level groups were presented in the Kaplan-Meier curve. The correlation between serum CPS1 level and HEV-ALF related conventional parameters was also analyzed by linear regression. The efficacy of serum CPS1 level on predicting the 30-day mortality of HEV-ALF patients was estimated by the receiver operating characteristic curve and area under curve (AUC). Results:Serum CPS1 level was significantly higher in HEV-ALF patients than in AHE patients [958.59 (665.52, 1 105.83) pg/ml vs 549.38 (495.02, 649.08) pg/ml, P<0.001], and serum CPS1 level was significantly higher in AHE patients than in healthy controls [549.38 (495.02, 649.08) pg/ml vs 469.89 (373.32, 564.53) pg/ml, P<0.001]. The level of serum CPS1 was significantly lower in the HEV-ALF survival group than in the HEV-ALF non-survival group [922.6 (652.7, 1, 042.3) pg/ml vs 1 252.8 (933.3, 1 555.8) pg/ml, P<0.001]. In addition, the survival time was shorter in the high serum CPS1 level group than in the low serum CPS1 level group [24.59 (22.11, 27.06) d vs 28.16 (26.25, 30.07) d, P=0.045]. Serum CPS1 levels were increased in the fluctuation and deterioration groups [Fluctuation: 1 328.3 (1 184.3, 1 964.0) pg/ml vs 1 245.7 (1 102.0, 1 937.6) pg/ml, P<0.01; Deterioration: 1 483.6 (1 275.9, 1 656.8) pg/ml vs 1 332.2 (1 197.4, 1 509.8) pg/ml, P<0.01], while decreased in the improvement group [810.3 (599.7, 904.5) pg/ml vs 922.6 (679.5, 1 039.6) pg/ml, P<0.01] over time. Besides, a linear positive correlation was found between serum CPS1 level and alanine aminotransferase (ALT) and total bilirubin (TBIL) (ALT: r=0.339, P<0.001; TBIL: r=0.304, P=0.002). The AUC of serum CPS1 level to predict the 30-day mortality of HEV-ALF patients was 0.803 (95% CI 0.666-0.941), the sensitivity and specificity were 66.67% and 97.47%, respectively. Conclusion:Serum CPS1 level was significantly increased in HEV-ALF patients, and closely related to the prognosis of patients with HEV-ALF.

Expert consensus on the process of in-hospital screening and management of viral hepatitis E in China (2023) / 临床肝胆病杂志

Hepatitis E caused by hepatitis E virus (HEV) infection is an acute /chronic infectious disease with significant morbidity and mortality, which has become an important global health issue. Our understanding of HEV has changed completely over the past decade. Every year 20 million people are infected with HEV, among whom hepatitis E occur in 3.3 million cases and 70 thousands die from HEV infection-related diseases globally. However, a majority of HEV infections, especially fulminant or chronic hepatitis E, are missed diagnosed or misdiagnosed in China. According the goal of eliminating viral hepatitis as a public health threat by 2030 set by the World Health Organization and based on the fact that medical institutions are the main facilities for diagnosis and treatment of Hepatitis E in China, we developed the Expert Consensus on the process of in - hospital screening and management of viral hepatitis E in China. The consensus intends to promote multi-disciplinary and multi-departmental collaboration in health care institutions, including hospital administration, infection control division, clinical departments and laboratory, to strengthen the screen, diagnosis, consultation, referral and treatment of patients with hepatitis E. Meanwhile, the consensus also intends to raise the awareness of hepatitis E among non-infectious and non-hepatic specialists, which would be conducive to timely detection and early diagnosis of hepatitis E.

Epidemiological characteristics of hepatitis A and hepatitis E in Jiaxing City from 2005 to 2021 / 预防医学

Objective@#To investigate the epidemiological characteristics of hepatitis A and hepatitis E in Jiaxing City, Zhejiang Province from 2005 to 2021, so as to provide insights into prevention and control of hepatitis A and hepatitis E.@*Methods@#Data of hepatitis A and hepatitis E reported in Jiaxing City from 2005 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The temporal, spatial and population distribution of hepatitis A and hepatitis E were analyzed using a descriptive epidemiological method, and the trends in incidence of hepatitis A and hepatitis E were evaluated using annual percent change (APC). @*Results@# Totally 1 830 hepatitis A cases were reported in Jiaxing City from 2005 to 2021, with an annual average incidence of 2.44/105, and 2 deaths were reported, with a fatality rate of 0.11%. The incidence of hepatitis A appeared a tendency towards a decline from 2005 to 2012 (APC=-37.807%, P<0.05) and was relatively stable from 2012 to 2021 (APC=-1.277%, P>0.05), and the incidence peaked from July to September, with a monthly average incidence of 0.30/105. Higher annual average incidence of hepatitis A was seen in urban areas than in rural areas (3.91/105 vs. 1.92/105; P<0.05), among people at ages of 30 to 39 years (4.19/105), and among men than among women (3.00/105 vs. 1.93/105; P<0.05). Farmers were the predominant occupation (759 cases, 41.31%). Totally 2 176 hepatitis E cases were reported in Jiaxing City from 2005 to 2021, with an annual average incidence of 2.91/105, and 7 deaths were reported, with a fatality rate of 0.32%. The incidence of hepatitis E was relatively stable from 2005 to 2011 (APC=3.421%, P>0.05) and appeared a tendency towards a decline from 2011 to 2021 (APC=-4.294%, P<0.05), and the incidence peaked from January to March, with a monthly average incidence of 0.38/105. Higher annual average incidence of hepatitis E was seen in urban areas than in rural areas (3.50/105 vs. 2.70/105; P<0.05), among people at ages of 70 to 79 years (6.20/105), and among men than among women (3.74/105 vs. 2.05/105; P<0.05). Farmers were the predominant occupation (1 079 cases, 49.59%).@*Conclusions@#The incidence of hepatitis A and hepatitis E appeared a tendency towards a decline in Jiaxing City from 2005 to 2021. The incidence of hepatitis A was high in summer, and cases were mainly males, young and middle-aged people and farmers. The incidence of hepatitis E was high in winter, and cases were mainly males, elderly people and farmers.

Prophylactic vaccines for hepatitis type E / 中华肝脏病杂志

Over the past few years, hepatitis type E has been increasingly recognized as an underestimated global disease burden. Populations with severe infection-related injuries or deaths include pregnant women, patients with underlying liver disease, and the elderly. Vaccines are the most effective means to prevent hepatitis type E virus (HEV) infection. However, the development of inactivated or attenuated vaccines is not feasible due to the lack of an efficient HEV cell culture system, so researchers have conducted in-depth research on recombinant vaccines. The capsid protein (pORF2), which the virion's open reading frame 2 encodes, contains almost exclusively the HEV neutralization site. Several candidate vaccines based on pORF2 have demonstrated potential for primate protection, with two being well tolerated and highly effective in preventing hepatitis type E in adults. Hecolin® (HEV 239 vaccine), the world's first hepatitis type E vaccine, was approved for marketing in China in 2012.

Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

Laboratory diagnosis of hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) infection is a common cause of acute viral hepatitis in China, and its etiological diagnosis relies on laboratory detection. Therefore, this article introduces the HEV RNA, HEV antigen, anti-HEV IgM, and IgG detection methods and their diagnostic application value. In addition, it also discusses the current international diagnostic standard and HEV infection presentation.

Research progress in the etiology of hepatitis type E virus / 中华肝脏病杂志

Hepatitis type E virus (HEV) is a significant infectious zoonotic disease that causes hepatitis E. The disease is primarily transmitted via the fecal-oral route through contaminated water or food and is transmissible between species and genera. The causative agent for the disease is the hepatitis type E virus, which is a member of the Hepadnaviridae family and a single-stranded RNA virus. Its 7.2 kb genome mainly contains three open reading frames (ORFs): ORF1 encodes a non-structural polyprotein that mediates viral replication and transcription; ORF2 encodes a capsid protein and free antigen that induce neutralizing antibodies; ORF3 partially overlaps with ORF2 and encodes a small multifunctional protein involved in virion formation and release. HEV has a unique dual life cycle: it is excreted into feces in the form of naked virions but circulates in the blood in the form of "quasi-enveloped" particles. The two kinds of virus particles adsorb and penetrate the host cell in distinct ways, then internalize and decapsulate to replicate the genome, thereby producing more virion and releasing it outside the cell to mediate the virus's spread. This paper reviews the morphological characteristics, genome structure, encoded proteins, and function of HEV virus-like particles in order to provide a theoretical basis for basic research and comprehensive disease prevention and control.

Advances in hepatitis E epidemiology / 中华肝脏病杂志

Hepatitis E is a viral hepatitis that the hepatitis E virus (HEV) causes. In the early 1980s, the hepatitis E virus was first discovered and identified, and it is one of the important pathogens that cause acute viral hepatitis globally. HEV infection is usually self-limiting, but in some groups of populations, such as pregnant women, patients with chronic liver disease, and the elderly, the prognosis is poor and may result in acute or subacute liver failure or even death. In addition, HEV infection can occur in chronically immunocompromised populations. At present, some regions and countries are not paying enough attention to hepatitis E prevention, diagnosis, and treatment, which suggests that we should study the epidemiology of HEV infection.

Strengthening the study of chronic hepatitis E / 中华肝脏病杂志

This paper summarizes the incidence, modes of transmission, diagnosis, treatment and prevention of chronic hepatitis E.

Assessment of hepatitis E seropositivity among HIV-infected patients in Bulgaria

Abstract It is debatable whether HIV-infected patients are at greater risk for hepatitis E virus (HEV) infection compared with healthy subjects. The reported anti-HEV seroprevalence among different groups in Bulgaria varied from 9.04% to 25.9%, but the information regarding the HIV population is still missing. The aim of the present study was to evaluate hepatitis E seroprevalence among HIV-infected patients in Bulgaria and to analyze demographic and immunological factors associated with HEV infection. Serum samples of 312 HIV-infected patients were analyzed retrospectively. Age, sex, residence and laboratory markers for HEV, HBV, HCV and HIV infection, and lymphocytes subpopulations were collected for all patients. None of the tested samples were positive for HEV RNA. HEV seroprevalence among HIV-infected patients was 10.9%. Males were more affected with the highest prevalence of positivity in the age group > 30 to ≤ 40 years. The documented HIV transmission routes in HIV/HEV co-infected group were heterosexual, homosexual, intravenous drug use (IDU), and vertical with predominace of the heterosexual route (z = 0.2; p = 0.804). There was a statistically significant trend of HIV mixed infection with routes of HIV transmission other than homosexual - heterosexual in HIV/HEV group and injection drug use in HIV/HBV/HCV co-infected group. The route of HIV transmission, in contexts of patients' behavior, was associated with HEV prevalence among HIV-infected patients.