• Enterovirus C
• PepSeq
• antibody repertoire
• health disparities
• hepatitis A virus
• highly multiplexed serology
• human adenovirus D
• human herpesviruses
• human immunodeficiency virus
• salivirus A
• virome
• virus

• Humans
• Male
• Female
• Virus Diseases/epidemiology
• Virus Diseases/diagnosis
• Middle Aged
• Adult
• Health Status Disparities
• Seroepidemiologic Studies
• Pilot Projects
• Viruses/genetics
• Viruses/classification
• Viruses/isolation & purification
• Serologic Tests/methods
• Virome/genetics

• U24 AI152172 NIAID NIH HHS
• U54 MD012388 NIMHD NIH HHS
• U54MD012388 HHS | National Institutes of Health (NIH)
• U24AI152172 HHS | National Institutes of Health (NIH)

• HBV
• HEV
• epidemiology
• hepatitis
• one health
• risk factors
• tropical forests

• HEV
• antiviral treatment
• chronic infection
• inhibitors
• pregnancy
• viral cell entry

• Humans
• Hepatitis E virus/physiology
• Hepatitis E virus/pathogenicity
• Hepatitis E/transmission
• Hepatitis E/virology
• Virion/physiology
• Animals

• hepatology
• hepatitis c virus
• viral epidemiology

• Adult
• Humans
• Male
• Middle Aged
• Aged
• Female
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/epidemiology
• Incidence
• Carcinoma, Hepatocellular
• Coinfection/epidemiology
• Prevalence
• Liver Neoplasms/epidemiology
• Hepatitis C
• Hepacivirus
• Hepatitis E virus
• Immunoglobulin G

• Korea Disease Control and Prevention Agency

• HEV
• calcineurin inhibitors
• graft hepatitis
• viral hepatitis
• viremia

Hepatitis E virus (HEV) causes not only acute and chronic hepatitis but also neurological disorders. To delineate the mechanism of HEV-associated neurological diseases, we showed that both quasi-enveloped and nonenveloped HEVs can cross the blood–brain barrier model in a tumor necrosis factor alpha (TNF-α)-independent manner and productively infect brain microvascular endothelial cells in vitro. Furthermore, we showed that HEV was detected in brain and spinal cord from HEV-infected pigs and that pigs with detectable HEV in central nervous system (CNS) tissues had histological lesions in brain and spinal cord and significantly higher levels of proinflammatory cytokines TNF-α and interleukin 18 than pigs without detectable HEV in CNS tissues. The results shed light on a potential mechanism of HEV-associated neuroinvasion.

Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and chronic viral hepatitis. A proportion of HEV-infected individuals also developed neurological diseases such as Guillain–Barré syndrome, neuralgic amyotrophy, encephalitis, and myelitis, although the mechanism remains unknown. In this study, by using an in vitro blood–brain barrier (BBB) model, we first investigated whether HEV can cross the BBB and whether the quasi-enveloped HEV virions are more permissible to the BBB than the nonenveloped virions. We found that both quasi-enveloped and nonenveloped HEVs can similarly cross the BBB and that addition of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has no significant effect on the ability of HEV to cross the BBB in vitro. To explore the possible mechanism of HEV entry across the BBB, we tested the susceptibility of human brain microvascular endothelial cells lining the BBB to HEV infection and showed that brain microvascular endothelial cells support productive HEV infection. To further confirm the in vitro observation, we conducted an experimental HEV infection study in pigs and showed that both quasi-enveloped and nonenveloped HEVs invade the central nervous system (CNS) in pigs, as HEV RNA was detected in the brain and spinal cord of infected pigs. The HEV-infected pigs with detectable viral RNA in CNS tissues had histological lesions in brain and spinal cord and significantly higher levels of proinflammatory cytokines TNF-α and interleukin 18 than the HEV-infected pigs without detectable viral RNA in CNS tissues. The findings suggest a potential mechanism of HEV-associated neuroinvasion.

• blood–brain barrier (BBB)
• brain microvascular endothelial cells
• central nervous system (CNS)
• hepatitis E virus (HEV)
• neurological disorder

• Americas
• Hepatitis E
• Hepatitis E virus
• Humans
• Immunoglobulin G
• Seroepidemiologic Studies

Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.

• Hepatitis E
• Hepatitis E virus
• Chronic hepatitis
• Acute hepatitis
• Immunocompromised
• Liver transplant

• alcoholic liver disease
• hepatitis B virus
• hepatitis C virus
• hepatitis E virus
• non-alcoholic fatty liver disease

• HCV
• HEV
• HIV
• prevalence
• seroconversion
• seroreversion

• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Treatment

• Hepatitis A
• Hepatitis, Viral, Human/diagnosis
• Hepatitis, Viral, Human/drug therapy
• Hepatitis, Viral, Human/epidemiology
• Humans
• Liver Transplantation
• Vaccination

Seroprevalence rates and molecular characterization of hepatitis E virus (HEV) prevalent in the Lithuanian human population has not yet been evaluated. Immunosuppressed individuals have been recognized as a risk group for chronic hepatitis due to HEV genotype 3 (HEV-3) infections. The objectives of the present study were to determine prevalence rates of anti-HEV antibodies among inflammatory bowel disease (IBD) patients and solid organ transplant (SOT) recipients, to isolate and characterize HEV strain present in the Lithuanian human population, and to investigate its capacity to infect non-human primate (MARC-145 and Vero), swine (PK-15) and murine (Neuro-2a) cells in vitro. In the present study, the significant difference of anti-HEV IgG prevalence between healthy (3.0% (95% CI 0–6.3)) and immunosuppressed individuals (12.0% [95% CI 8.1–15.9]) was described. Moreover, our findings showed that anti-HEV IgG seropositivity can be significantly predicted by increasing age (OR = 1.032, p < 0.01), diagnosis of IBD (OR = 4.541, p < 0.01) and reception of SOT (OR = 4.042, <0.05). Locally isolated HEV strain clustered within genotype 3i subtype of genotype 3 and was capable of infecting MARC-145 cells. This study demonstrates higher HEV seroprevalence in the risk group compared to healthy control individuals without confidence interval overlap. The high level of genetic homology between human and animal strains in Lithuania and the capacity of locally isolated strains to infect cells of non-human origin suggests its potential for zoonotic transmission.

• Crohn’s disease
• MARC-145
• biological therapy
• genotype 3
• hepatitis E
• immunosuppression
• inflammatory bowel disease
• solid organ transplant
• ulcerative colitis
• zoonosis

Hepatitis E virus (HEV) is a major cause of viral hepatitis around the world, especially in developing countries. Recently, HEV has also been recognized as important cause of hepatitis in Europe and Japan, however, there is a paucity of clinical data from the United States. The overall seroprevalence of HEV antibodies is around 10% in the United States, but considerable variation is seen based on geographic location, year, and assay used. In this study, 63 adults and 417 children from New York State were tested for anti-HEV IgG antibodies using the commercially available Wantai IgG assay. The overall seroprevalence of HEV antibodies among adult participants was 9.52% (95% CI: 3.58–19.59%). Positive adults tended to be older than HEV negative adults, all positive adults were female. Only 3 (0.7%, 95% CI:: 0.15–2.09%) of the children were positive, all positive children were male. These results are consistent with global and United States trends in HEV seroprevalence.

• Adolescent
• Adult
• Antibodies, Viral/blood
• Antibodies, Viral/immunology
• Child
• Female
• Hepatitis E/blood
• Hepatitis E/epidemiology
• Hepatitis E virus/immunology
• Humans
• Male
• Middle Aged
• New York
• Seroepidemiologic Studies
• Serologic Tests/statistics & numerical data

• R01 ES023252 NIEHS NIH HHS
• Project: Time Off (US)
• Foundation for the National Institutes of Health
• David B. Falk College of Sport and Human Dynamics (US)

• hepatitis E virus
• incidence
• prevention
• trend

• Guillain-Barre syndrome
• antiganglioside antibodies
• extrahepatic manifestations
• hepatitis E virus
• infections
• peripheral neuropathies
• viral replication

• Autoimmunity
• Disease Management
• Guillain-Barre Syndrome/etiology
• Guillain-Barre Syndrome/virology
• Hepatitis E/complications
• Hepatitis E/immunology
• Hepatitis E virus/immunology
• Hepatitis E virus/pathogenicity
• Humans

• 81200834 National Nature Science Foundation for Young Scholars of China

• Hematologic malignancy
• Hematologic neoplasms
• Hepatitis E
• Hospitalizations
• Inpatients
• Non-Hodgkin Lymphoma
• Viral hepatitis

Hepatitis E virus (HEV) has been scarcely investigated in the Indian Ocean. Following a nationwide serosurvey among blood donors, we conducted a population-based serosurvey to assess the magnitude of HEV exposure on Reunion Island.

Four hundred and sixty-six archived frozen human sera from the 2009 CoPanFlu-RUN cohort were analysed using the Wantai HEV IgG enzyme immunoassay. HEV seropositivity was defined as an IgG titre ≥5 UI/ml. Raw and weighted seroprevalences were assessed to account for the discrepancy between the CoPanFlu-RUN subset and the general community. Prevalence proportion ratios (PPR) were measured using log-binomial models.

The raw and the weighted seroprevalences of HEV were 9.01% (95% CI 6.41–11.61) and 6.73% (95% CI 4.47–8.98), respectively. The presence of HEV IgG antibodies was associated with increasing age (P < 0.001). In a survey-adjusted model minimizing the sampling bias and adjusting for age, males were more likely to be seropositive than females (adjusted PPR 2.59, 95% CI 1.07–6.25). Seropositivity was spatially heterogeneous across the island (P < 0.01). Living in the neighbourhood of a pig farm within a low to intermediate slope area was associated with seropositivity in several models adjusting for age, gender, altitude of residency and interaction between slope and pig farms.

Reunion Island is a low endemic area for HEV exposure. Despite limitations related to the retrospective study design, our findings confirm the roles of cumulative lifetime exposure and male gender in HEV exposure. The risk associated with neighbouring pig farms might also suggest environmental contamination in this setting.

• General population
• Hepatitis E
• Immunoassay
• Pig farm
• Prevalence
• Seroepidemiological study
• Serology
• Serosurvey
• Stored frozen serum
• Zoonosis