• acute pancreatitis
• bell's palsy
• cholestatic jaundice
• extrahepatic manifestations
• hepatitis e

• Challenges
• Chronic hepatitis E
• Hepatitis E virus
• Post-transplant hepatitis
• Risk factors

• Antiviral therapy
• Chronic hepatitis
• Hepatitis E
• Screening
• Vaccination

• Cirrhosis
• Hepatitis
• Liver failure
• Nephropathy
• Renal Failure

• Animal reservoir
• Climate change
• Food safety
• Hepatitis E virus
• Host range
• Zoonosis

• Hepatitis E virus
• Viral life cycle
• Virus–host interactions

• Animals
• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Cell Culture Techniques
• Hepatitis E virus/genetics
• Immunocompromised Host
• Life Cycle Stages
• Subgenomic RNA/genetics

Hepatitis E virus (HEV) is one of the most important public health issues around the world, and chronic HEV infection has been reported in immunosuppressed individuals. This study reported a male case, with very severe aplastic anemia (AA), who developed chronic hepatitis E after hematopoietic stem cell transplantation (HSCT). Abnormal alanine aminotransferase (ALT) appeared after HSCT and persisted for twenty-nine months. The case was seropositive for anti-HEV IgG and IgM after HSCT. Twenty-two months after HSCT, HEV RNA and antigen (Ag) testing were positive and persisted for five and seven months, respectively. Positive stains of HEV Ag were present in a liver biopsy sample. HEV Ag was present in bone marrow. The individual rapidly developed liver cirrhosis and was rescued by a regimen of oral ribavirin. These factors suggested there is a risk of HEV infection in HSCT recipients.

• Male
• Humans
• Hepatitis E virus/genetics
• Hepatitis E/diagnosis
• Hepatitis E/drug therapy
• Ribavirin/therapeutic use
• Alanine Transaminase
• Persistent Infection
• Hematopoietic Stem Cell Transplantation/adverse effects
• Immunoglobulin G/genetics
• Immunoglobulin M/genetics
• RNA
• Genotype

• Academy of Medical Sciences

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis. The disease takes a severe form in pregnant women, leading to around 30% mortality. Zinc is an essential micronutrient that plays a crucial role in multiple cellular processes. Our earlier findings demonstrated the antiviral activity of zinc salts against HEV infection. Zinc oxide (ZnO) and its nanostructures have attracted marked interest due to their unique characteristics. Here we synthesized ZnO nanoparticles [ZnO(NP)] and tetrapod-shaped ZnO nanoparticles [ZnO(TP)] and evaluated their antiviral activity. Both ZnO(NP) and ZnO(TP) displayed potent antiviral activity against hepatitis E and hepatitis C viruses, with the latter being more effective. Measurement of cell viability and intracellular reactive oxygen species levels revealed that both ZnO(NP) and ZnO(TP) are noncytotoxic to the cells even at significantly higher doses, compared to a conventional zinc salt (ZnSO₄). Our study paves the way for evaluation of the potential therapeutic benefit of ZnO(TP) against HEV and HCV.

• Indian Council of Medical Research

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

• Acute liver failure
• Hepatitis E
• Mortality prediction
• Nomogram
• Scoring model

Infection with the hepatitis E virus (HEV) is one of the main ubiquitous causes for developing an acute hepatitis. Moreover, chronification plays a predominant role in immunocompromised patients such as transplant recipients with more frequent severe courses. Unfortunately, besides reduction of immunosuppression and off-label use of ribavirin or pegylated interferon alfa, there is currently no specific anti-viral treatment to prevent disease progression. So far, research on involved immune mechanisms induced by HEV is limited. It is very difficult to collect clinical samples especially from the early phase of infection since this is often asymptomatic. Nevertheless, it is certain that the outcome of HEV-infected patients correlates with the strength of the proceeding immune response. Several lymphoid cells have been identified in contributing either to disease progression or achieving sustained virologic response. In particular, a sufficient immune control by both CD4⁺ and CD8⁺ T cells is necessary to prevent chronic viral replication. Especially the mechanisms underlying fulminant courses are poorly understood. However, liver biopsies indicate the involvement of cytotoxic T cells in liver damage. In this review, we aimed to highlight different parts of the lymphoid immune response against HEV and point out questions that remain unanswered regarding this underestimated global threat.

• T cells
• hepatitis E virus
• innate lymphoid cells
• natural killer T cells
• natural killer cells
• solid organ transplantation

• Animals
• Hepatitis E/epidemiology
• Hepatitis E/immunology
• Hepatitis E/virology
• Hepatitis E virus/immunology
• Humans
• Immunity/immunology
• Immunocompromised Host
• Pandemics
• Sustained Virologic Response
• Virus Replication

Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host’s innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.

• hepatitis E virus
• inflammation
• innate immune response
• interferon
• interferon-stimulated genes
• pattern recognition receptors

• ORF1
• adaptive evolution
• codon usage
• cross-species transmission
• hepatitis E virus
• host cellular factor
• pathogenesis

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide. HEV infection is not limited only to liver but has various extrahepatic manifestations. Virus can affect various organs like pancreas, lymph nodes, hematological system, kidneys, spleen, central, and peripheral nervous system. We hereby present a case of 19-year-old patient with interesting finding on magnetic resonance imaging brain-related with hepatitis E.

• corpus callosum hyperintensity
• extra-hepatic involvement
• hepatitis E virus
• neurological involvement

• Hepatitis E in pregnancy
• Hepatitis E virus (HEV)
• life cycle
• pathogenesis
• virology
• virus-cell interactions

• adult patients
• antiviral treatment
• hepatitis E virus
• pediatric patients
• prevention

• hepatitis and other GI infections
• infectious diseases
• meningitis

Background: We conducted a systematic review in order to summarize the available data on pancreatitis associated with viral hepatitis. Methods: A comprehensive literature search of Medline, Scopus and ISI Web of Science databases was conducted and papers eligible for the inclusion identified. Results: In total, 46 studies reporting data on 73 patients were included in the analysis. Most of the cases were diagnosed in Asia (57.53%), followed by North America (23.29%), and Europe (13.70%). Most of the patients were affected by hepatitis A virus (HAV) (42.47%), followed by hepatitis E virus (HEV) (28.77%), hepatitis B virus (HBV) (8.22%), and hepatitis C virus (HCV) (1.37%), while 17.81% at the time of diagnosis were classified as affected by “hepatitis virus”. Pancreatitis was severe in 32.88% of cases. The respiratory system was affected in 2.74% of patients, 6.85% experienced renal failure, while 5.48% experienced a multiorgan dysfunction syndrome (MODS). Four patients (5.48%) needed pancreatic surgery. Despite the treatment, 21.92% of patients died. We identified fulminant hepatitis (p < 0.0001), MODS (p < 0.0001) and severe pancreatitis (p < 0.0001) to be significantly more present in patients who died in comparison to cured ones. Conclusion: Increased awareness of pancreatic involvement in viral hepatitis is needed because it can have a substantial impact on therapeutic approaches and outcomes.

• hepatitis
• pancreatitis
• viral

The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

• Hepatitis E
• Hepatitis E virus
• Extrahepatic manifestations
• Zoonotic infection
• Chronic hepatitis
• Acute hepatitis

• Aged
• Aged, 80 and over
• Animals
• Antiviral Agents/therapeutic use
• Female
• Hepatitis E/diagnosis
• Hepatitis E/drug therapy
• Hepatitis E/epidemiology
• Hepatitis E virus/genetics
• Hepatitis, Chronic/drug therapy
• Humans
• Pregnancy
• Ribavirin/therapeutic use
• Swine

• Hepatitis E
• Hepatitis E virus (HEV)
• Pregnancy

HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations.

• HEV infection
• PBMCs
• bone marrow
• capsid protein
• chronic
• ds-RNA
• extrahepatic
• hematological disorders
• immune response

Understanding the dynamics of host innate immune responses against a pathogen marks the first step toward developing intervention strategies against the pathogen. The cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) has been shown to be the major innate immune sensor for hepatitis E virus (HEV). Here, we show that HEV capsid protein (ORF2), a 660 amino acid long protein, interferes with the RIG-I signaling. Interestingly, only the full length ORF2 protein but not the 112-608 ORF2 protein inhibited RIG-I dependent interferon response. Both synthetic agonist and virus induced RIG-I activation was modulated by ORF2. Interference of interferon response was confirmed by reporter assays involving different interferon inducible promoters, qRT PCR, ELISA, and immunofluorescence microscopy. Neither glycosylation nor dimerization of the ORF2 protein had any effect on the observed inhibition. Further analyses revealed that the ORF2 protein antagonized Toll-like receptor (TLR) pathways as well. ORF2 inhibited signaling by RIG-I and TLR adapters, IPS-1, MyD88, and TRIF but was unable to inhibit activation by ectopically expressed IRF3 suggesting that it may be acting at a site upstream of IRF3 and downstream of adapter proteins. Our data uncover a new mechanism by which HEV may interfere with the host antiviral signaling.

• HEV
• ORF2
• RIG-I
• innate immunity
• interferon

Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.

• HEV
• PCR
• hepatitis E
• immunosuppression
• serology

• HEV
• extra-hepatic manifestations
• hepatitis E
• viral hepatitis

• Acute-on-chronic liver failure
• Hepatitis E
• acute decompensation
• liver transplantation
• viral hepatitis

• Acute Disease
• Chronic Disease
• Hepatitis E/diagnosis
• Hepatitis E/therapy
• Humans

Hepatitis E virus (HEV) is a significant health problem with approximately 20 million individuals infected annually. HEV infection has been associated with a wide spectrum of extrahepatic manifestations, including neurological, hematological and renal disorders. Guillain-Barré syndrome and neuralgic amyotrophy are the most frequent neurological manifestations. In addition, HEV infection has been observed with other neurological diseases, such as encephalitis, myelitis and Bell’s palsy. Hematologic manifestations include anemia due to glucose-6-phospate dehydrogonase deficiency, autoimmune hemolytic anemia and severe thrombocytopenia. Membranoproliferative glomerulonephritis and relapse IgA nephropathy with or without coexisting cryoglobulinemia appear to be the most common renal injuries related with HEV infection. Also, HEV infection has been associated with acute pancreatitis and other immune-mediated manifestations, such as arthritis and myocarditis. However, the pathophysiologic mechanisms of HEV-related extrahepatic manifestations are still largely unclear.

• Hematologic diseases
• Hepatitis E
• Kidney
• Neurologic manifestations

Extrahepatic manifestations of Hepatitis E, though rare, are being increasingly reported in the medical literature. In this review article, we will discuss the extrahepatic manifestations of hepatitis E, such as Guillain-Barre syndrome, pancreatitis, and cryoglobulinemia, their clinical association with hepatitis E, and their management.

• extrahepatic manifestations
• guillain-barré syndrome (gbs)
• hepatitis e
• mixed cryoglobulinemia
• pancreatitis

Hepatitis E is a common, mainly water-borne hepatotropic virus prevalent mainly in Southeast Asia, Africa, the Middle East, and Central America. In the eastern part of India epidemics of acute hepatitis E are well reported. Hepatitis E commonly presents as self-limiting acute viral hepatitis among young adults, except for some critical clinical complications during pregnancy. In epidemiological research, subclinical acute hepatitis E infection is also reported from different parts of the world, including developed nations such as the USA (predominantly in the population aged >60 years). Though primarily hepatotropic, in the literature there are reports of rare extrahepatic manifestation of acute hepatitis E. Here we present an elderly lady with acute hepatitis E who primarily presented with acute myocarditis.

• Dilated cardiomyopathy
• Elderly woman
• Hepatitis E
• Myocarditis

• cutaneous vasculitis
• fibrinoid necrosis
• hepatitis E virus
• leukocytoclastic vasculitis

• Cross-sectional study
• Genotype
• Hepatitis E virus (HEV)
• Seroepidemiological study
• Zoonosis

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Animals
• Child
• Child, Preschool
• China/epidemiology
• Cross-Sectional Studies
• Farmers
• Female
• Genotype
• Hepatitis Antibodies/blood
• Hepatitis E/epidemiology
• Hepatitis E/immunology
• Hepatitis E/veterinary
• Hepatitis E virus/genetics
• Humans
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Prevalence
• RNA, Viral/blood
• Seroepidemiologic Studies
• Swine
• Swine Diseases/epidemiology
• Swine Diseases/immunology
• Swine Diseases/virology
• Young Adult
• Zoonoses/epidemiology
• Zoonoses/immunology
• Zoonoses/virology

• Acute Disease
• Female
• Genotype
• Global Health
• Hepatitis E/complications
• Hepatitis E/epidemiology
• Hepatitis E/transmission
• Hepatitis E virus/genetics
• Humans
• Infant
• Infant, Newborn
• Infectious Disease Transmission, Vertical
• Liver/pathology
• Liver/virology
• Liver Failure, Acute/etiology
• Nervous System Diseases/virology
• Pregnancy
• Pregnancy Complications, Infectious/epidemiology
• Pregnancy Complications, Infectious/virology

The course of hepatic diseases may be complicated by a multitude of rheumatologic manifestations, which can complicate the diagnostic approach and alter the natural history of primary liver disease, sometimes worsening prognosis due to associated multiple organ dysfunction. These manifestations can occur in association with a multitude of liver diseases, including viral hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, hemochromatosis, or Wilson’s disease. It is necessary not only for rheumatologists, but also for other clinicians, to be aware that these atypical manifestations may reflect an undiagnosed hepatic disease. On the other hand, it is crucial that, in a patient with known hepatic disease presenting with rheumatologic symptoms, an accurate distinction be made between the rheumatologic manifestations of hepatic disease and primary rheumatologic disease, since the treatment is often different. This review aims to summarize the current evidence regarding rheumatologic manifestations of hepatic diseases, how to distinguish them from primary rheumatologic disorders, and how to provide adequate management.

• Rheumatologic manifestations
• arthritis
• hepatic diseases
• hepatitis

• evolution
• genetic variability
• genotypes
• hepatitis E virus

• Animals
• Evolution, Molecular
• Genetic Variation
• Genome, Viral
• Genomics/methods
• Genotype
• Hepatitis E/virology
• Hepatitis E virus/classification
• Hepatitis E virus/genetics
• Humans
• Phylogeny

• Croatia
• Hepatitis E virus genotyping
• Human
• Swine
• Wild boar

• Animals
• Croatia
• Feces/virology
• Genetic Variation/genetics
• Hepatitis E/epidemiology
• Hepatitis E/veterinary
• Hepatitis E/virology
• Hepatitis E virus/genetics
• Humans
• RNA, Viral/analysis
• RNA, Viral/blood
• RNA, Viral/genetics
• Sus scrofa/virology
• Swine/virology
• Swine Diseases/epidemiology
• Swine Diseases/virology

• Guillain-Barré syndrome
• Hepatitis E virus
• genotype
• sofosbuvir

Infection induced kidney diseases are of concern for clinicians because timely detection and treatment of infections may cure or limit the extent of injury inflicted by microorganisms causing the infections. Infections can cause kidney injury by either direct invasion, or indirectly by immune mediated mechanisms, which manifest as post-infectious glomerulonephritis, or infection-related glomerulonephritis. Clinical manifestations may be acute or chronic depending on the microorganisms, endemic/epidemic nature and source of infection. All microbials virus, bacteria, mycobacteria, fungus, and protozoa have been implicated in kidney diseases either causing direct kidney injuries or immune-mediated injuries. Infection control practices in large parts of world is limited by poverty, social behavior, high population density, deforestation, inadequate access to safe drinking water, and poor health care facilities. Although, antimicrobials and vaccinations have successfully eradicated and cured many infectious diseases; however injudicious antimicrobial use and emergence of resistant organisms complicated the disease severity like secondary renal amyloidosis with chronic persistent infection. Re-emergence of various infections has been a recent pattern in developed world leading to uncertain diagnostic challenges, and association with kidney diseases.

• glomerular injuries
• glomerulonephritis
• infections
• nephropathy
• prevention

• Autochthonous
• Hepatitis E virus
• New Zealand
• Transmission routes

• Animal Diseases/virology
• Animals
• Deer/virology
• Developed Countries
• Disease Transmission, Infectious
• Drinking Water/virology
• Feces/virology
• Foodborne Diseases/virology
• Hepatitis E/transmission
• Hepatitis E/virology
• Hepatitis E virus/growth & development
• Humans
• Meat/virology
• New Zealand
• Swine/virology
• Waterborne Diseases/virology
• Zoonoses/virology

• hepatitis and other gi infections
• hepatitis other
• infection (neurology)
• neurology

• Acute Disease
• Adult
• Female
• Hepatitis E/complications
• Hepatitis E/virology
• Hepatitis E virus
• Hot Temperature
• Humans
• Hypesthesia/virology
• Paresthesia/virology

Hepatitis E virus (HEV) infection is relatively high in the southern regions of China. Yunnan, located in southwestern China, has the highest number of ethnic groups. However, HEV infection in the ethnic population is largely unknown. Therefore, we aimed to investigate the seropositive rate, risk factor, and clinical impact of HEV infection in the ethnic groups of Yunnan. We recruited 1912 individuals from four minority groups in three prefectures of Yunnan province. Epidemiological records on potential risk factors for exposure to HEV and blood biochemical index were analyzed. All the serum samples were tested for anti-HEV IgM/IgG by enzyme-linked immunosorbent assay, and the IgM-positive samples were subjected to nested reverse transcription-PCR to detect HEV RNA. Overall, 1273 individuals (66.58%) were positive for anti-HEV IgG, 16 (0.84%) for anti-HEV IgM, and 64 (3.35%) for anti-HEV IgG and IgM both; none of them had detectable HEV RNA. Multivariate analysis revealed a strong statistical association between ethnic origin and HEV IgG seroprevalence. Anti-HEV IgG reactivity in the Hani ethnic (82.3%; 401/487) population was higher than that in the Naxi (71.9%, 340/473), Bulang (65.1%; 302/464), and Wa (60.2%; 294/488) ethnic populations (p < 0.0001). Older age and male sex were independently associated with the risk of past HEV infection. Moreover, anti-HEV IgG-positive individuals showed significantly higher levels of total and direct bilirubin and alanine amino transferase but significantly lower levels of globulin and low-density lipoprotein, than the respective levels in anti-HEV IgG-negative individuals. Thus, the seroprevalence of HEV infection is high in the ethnic populations of Yunnan, China. It is therefore necessary to increase the surveillance of specific risk groups and raise awareness about the possible infectious diseases to help limit the HEV transmission here.

• Animals
• Cells, Cultured
• Disease Models, Animal
• Global Health
• Hepatitis E/epidemiology
• Hepatitis E/therapy
• Hepatitis E/transmission
• Hepatitis E virus/chemistry
• Hepatitis E virus/genetics
• Hepatitis E virus/physiology
• Hepatocytes/virology
• Pluripotent Stem Cells/virology
• Viral Hepatitis Vaccines
• Viral Proteins/physiology
• Viral Tropism/physiology
• Virion/chemistry
• Virion/physiology

• R21 AI117213 NIAID NIH HHS

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain–Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection.

We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient’s neurological condition improved rapidly.

HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes.

The online version of this article (10.1186/s12879-018-2959-2) contains supplementary material, which is available to authorized users.

• Extra-hepatic manifestations
• Guillain–Barre syndrome
• Hepatitis E infection
• Viral hepatitis

• apoptosis
• hepatitis E virus
• ovary
• vertical transmission
• viral replication

• islets
• virus
• zoonosis

• hepatitis E virus

• Antiviral Agents/pharmacology
• Carcinoma, Hepatocellular/enzymology
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/virology
• Hepatitis E/drug therapy
• Hepatitis E/virology
• Hepatitis E virus/drug effects
• Hepatitis E virus/enzymology
• Hepatitis E virus/genetics
• Humans
• Liver Neoplasms/enzymology
• Liver Neoplasms/pathology
• Liver Neoplasms/virology
• RNA, Viral/genetics
• RNA-Dependent RNA Polymerase/antagonists & inhibitors
• Tumor Cells, Cultured
• Virus Replication/drug effects
• Zinc Compounds/pharmacology

Hepatitis E virus (HEV) is known as zoonotic agent. The main reservoirs of HEV in Europe are pigs, wild boars, and deer. Hunting activity is considered to be a risk factor for HEV infection. We conducted a cross-sectional study among 1021 Polish hunters. To understand socio-demographic characteristics of this population and to gather information on potential exposures, all participants completed a questionnaire. Commercial immunoassays were employed to estimate seroprevalence anti-HEV. Samples with confirmed positive result of anti-HEV IgM were examined for HEV RNA. Anti-HEV IgG were identified in 227 people, 22.2% of the studied group. Seroprevalence among the studied hunters was associated with age ≥65 [adjusted prevalence ratio (aPR) 1.6, p = 0.037), living in a house (aPR 1.54, p = 0.013), professional contact with farm animals (aPR 1.09, p = 0.01), and consumption of stewed offal (aPR 1.61, p = 0.00). Washing hands after disembowelment was linked to lower seroprevalence (aPR 0.53; p = 0.00). Lower prevalence of anti-HEV IgG among hunters living in cities was associated with age: 35–49 (aPR 0.52, p = 0.011) and 50–64 (aPR 0.93, p = 0.58), living in a house (aPR 1.58, p = 0.002) and owning a cat (aPR 0.58, p = 0.042). Among hunters living in rural areas, seropositivity was associated with contact with farm animals (aPR 1.66, p = 0.013) and consumption of stewed offal (aPR 1.81; p = 0.001). Contrary to initial assumptions, it was concluded that hunting was of significantly lesser importance than other factors. Due to the high level of HEV seroprevalence identified, we recommend conducting a large-scale study in the general population of Poland.

• Epidemiology
• Foodborne viruses
• Hepatitis E (HEV)
• Hunters
• Zoonosis

Background and aim: Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship.

Methods: An experienced librarian conducted a search of databases from each database’s inception to 12 December 2016 based on a priori criteria. The risk of bias was assessed, and Hill’s criteria were applied to determine causality.

Results: Five publications met inclusion criteria, with a total of 15 cases. Three studies had low, one low to moderate and one moderate risk of bias. Median age was 43 years, and all patients came from Western Europe. Two patients were immunocompetent, while 13 were immunosuppressed, post solid organ transplant and had chronic hepatitis E. Renal involvement was observed in seven patients, mild to moderately severe cryoglobulinemic disease in one patient and severe cryoglobulinemic disease in three patients. One patient improved spontaneously, and another was treated with immunosuppressant reduction leading to viral clearance. Ten patients treated with peg-interferon or ribavirin for 3 months achieved loss of cryoglobulinemia and end-of-treatment response, but sustained virologic response was reported and achieved in two. Immunosuppressant achieved loss of cryoglobulinemia in three patients. One case of chronic renal failure, three cases of end-stage renal disease and one death were observed. Five of the nine Hill’s criteria were fulfilled.

Conclusion: MC has been described with HEV infection. A causal relationship between HEV infection and cryoglobulinemia is highly probable.

• hepatitis
• hepatitis E virus
• mixed cryoglobulinemia
• systematic review
• virology