Submit to Pathogens Review for Pathogens Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Hepatitis E Virus (HEV) Infections

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 36978

Share This Special Issue

Special Issue Editor

Prof. Dr. Claus-Thomas Bock

E-Mail Website
Guest Editor

Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
Interests: molecular virology; viral hepatitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Hepatitis E virus (HEV) is the predominant cause of an enterically acquired acute viral hepatitis with an estimated 20 million infections worldwide and 44,000 associated deaths each year. HEV is highly endemic in resource limited countries where the virus is spread through the fecal-oral route during large waterborne outbreaks. Current HEV outbreaks of 2018/2019 were reported to the World Health Organisation (WHO) from West-Africa. HEV is increasingly recognized as an emerging disease in industrialized nations since an increasing number of locally acquired (autochthone) human hepatitis E cases has been recognized raising considerable concern. In addition to the water-/food borne associated transmission pattern there is clear evidence indicating that HEV is a zoonotic pathogen, which can infect humans through consumption of undercooked meat of infected domestic pigs and wild animals. Therefore, it has become evident that the disease may represent a significant global health burden.

However, the understanding of the zoonotic potential and detailed epidemiological data of HEV infections is still improvable.

The course of HEV infection in immunocompetent individuals is most often asymptomatic. When presenting with symptoms, hepatitis E usually manifests as a mild and self-limiting disease; however, the overall mortality rate may be 1-3% in general populations. Certain risk populations such as persons with pre-existing liver diseases and pregnant women may develop severe complications including fulminant hepatic failure, pre-term labor and increased incidence of fetal and maternal death with a fatality rate of up to 30%.

The mechanisms leading to different clinical outcome of HEV infection especially in pregnant is not well understood and needs further input and investigation.

In immunocompromised persons, such as solid organ and hematopoietic stem cell transplant recipients, HEV infections can develop into a chronic progression and affected patients may have worse prognoses. Although the antiviral drug ribavirin (RBV) is used as an off-label treatment to a degree of success in treated patients, side effects often pose limitations. Prolonged treatment can select viral mutants that are less susceptible to RBV. Predicting chronicity of HEV infection, i.e., with characteristic biomarkers, and thus administering antiviral therapy as early as possible would pose a valuable opportunity for increased patient care and control of disease outcome.

Thus new insights into mechanisms leading to chronic hepatitis E and innovative antiviral treatment options are still needed.

Extrahepatic manifestation of HEV infection has been reported most commonly of the nervous system and the kidney while, e.g., Guillain-Barre syndrome, neuralgic amyotrophy, glomerulonephritis, meningitis, encephalitis, or myopathy could be associated with hepatitis E.

However, underlying mechanisms of the different manifestation and clinical outcome of extrahepatic HEV infection are still underreported but is of high interest.

Although HEV replication is thought to be controlled by the host immune system, viral factors (genotypes and mutants, virus diversity, virus evolution) can modulate HEV replication, infection and pathogenesis.

Limited knowledge exists on the contribution of virus-host interaction and HEV genome variants towards pathogenesis, immunological response, replication control and susceptibility to antiviral drugs; however, this limitation has to be reduced incrementally.

In this Special Issue, we will summarize the current knowledge answering the many open questions albeit in part on HEV infection in terms of virological, immunological, one health (zoonosis) and global health level, in order to improve our knowledge on HEV pathogenesis, immunology, epidemiology and factors that influence HEV replication, chronification and risk assessment in humans and animals.

We thus invite submission of research and review manuscripts that cover any aspect of the pathogenesis, immunology, epidemiology, diagnosis, treatment and prevention of hepatitis E. I look very forward to your contributions which will give without any doubt a valuable and high ranking edition that will promote further developments in the exciting field of hepatitis E.

Thank you for your collaboration.

Prof. Dr. C. Thomas Bock
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Virology
- HEV Virology & Pathogenicity
- Immunology
One Health - HEV in Animals
- HEV Zoonosis & Transmission
- HEV Food and Blood product Safety
- Prevention & Therapy
Global Health - HEV Epidemiology & Natural History
- HEV Diversity
- HEV Diagnostics
- Clinical outcome & Chronic HEV
- Risk Assessment & Gender Specificity
- Extrahepatic Manifestation

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review, Other

8 pages, 1109 KiB

Open AccessArticle

Control of Raw Pork Liver Sausage Production Can Reduce the Prevalence of HEV Infection

by Paolo Ripellino, Enea Pianezzi, Gladys Martinetti, Cinzia Zehnder, Barbara Mathis, Petra Giannini, Nicola Forrer, Giorgio Merlani, Harry R. Dalton, Orlando Petrini, Florian Bihl, Stefano Fontana and Claudio Gobbi

Pathogens 2021, 10(2), 107; https://doi.org/10.3390/pathogens10020107 - 22 Jan 2021

Cited by 5 | Viewed by 2248

Abstract

After an acute hepatitis E (HEV) outbreak in Southern Switzerland, in January 2017 the local public health authorities started an active program of food chain control and public education. In this retrospective study, we analysed all laboratory-confirmed acute cases of HEV infection diagnosed between 2014 and 2020. In the period before the public health intervention, the number of cases increased steadily from 2014 (4 of 40 tests, 10%) reaching a peak in the last quarter of 2016 (42 of 285 tests, 14.7 %). Afterwards, the number of positive cases decreased steadily, reaching its lowest value (0.3%) in the second quarter of 2019. There was a statistically significant difference between the frequency of positive cases and period of testing, i.e., before and after the introduction of the public health interventions. Our study shows that active public health measures to control sausages containing raw pork liver can reduce the prevalence of HEV infection. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

19 pages, 4519 KiB

Open AccessArticle

Clinical Characteristics of Acute Hepatitis E and Their Correlation with HEV Genotype 3 Subtypes in Italy

by Claudia Minosse, Elisa Biliotti, Daniele Lapa, Alessia Rianda, Mauro Marchili, Ilaria Luzzitelli, Maria Rosaria Capobianchi, Fiona McPhee, Anna Rosa Garbuglia and Gianpiero D’Offizi

Pathogens 2020, 9(10), 832; https://doi.org/10.3390/pathogens9100832 - 11 Oct 2020

Cited by 8 | Viewed by 2154

Abstract

Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

12 pages, 609 KiB

Open AccessArticle

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

by Thomas Horvatits, Julian Schulze zur Wiesch, Susanne Polywka, Gustav Buescher, Marc Lütgehetmann, Elaine Hussey, Karoline Horvatits, Sven Peine, Friedrich Haag, Marylyn M. Addo, Ansgar W. Lohse, Christina Weiler-Normann and Sven Pischke

Pathogens 2020, 9(9), 755; https://doi.org/10.3390/pathogens9090755 - 16 Sep 2020

Cited by 8 | Viewed by 2802

Abstract

Background: Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection. Methods: The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. Results: Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors (p = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients. Conclusion: In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

8 pages, 226 KiB

Open AccessArticle

Seroprevalence of Hepatitis E Virus in Forestry Workers from Trentino-Alto Adige Region (Northern Italy)

by Marina Monini, Fabio Ostanello, Alessandra Dominicis, Valentina Tagliapietra, Gabriele Vaccari, Annapaola Rizzoli, Claudia M. Trombetta, Emanuele Montomoli and Ilaria Di Bartolo

Pathogens 2020, 9(7), 568; https://doi.org/10.3390/pathogens9070568 - 14 Jul 2020

Cited by 6 | Viewed by 2042

Abstract

People with some occupational or recreational activities, such as hunters and veterinarians, may have increased risk to be infected by the hepatitis E virus (HEV). The aim of the present study was to establish whether forestry workers could be considered at a higher risk of HEV infection than a control group. One hundred and fifty sera from forestry workers and a control group of 85 sera were analysed by anti-HEV IgG antibodies detection using a commercial ELISA kit. The anti-HEV IgG seroprevalence was 14% for forestry workers and 9.4% for the control group. Comparing the risk of HEV infection in the two groups, there was no difference in the odds ratio. However, the seroprevalence in older subjects was higher in the forestry workers than in the control group. Two sera from forestry workers were also positive for anti-HEV IgM, and, in one of them, HEV-RNA was detected. Our findings showed an increase of seroprevalence with age, which is likely to reflect cumulative exposure to HEV over time. The occupation of forestry workers did not seem to be associated with a higher risk of HEV infection. The study provided new insights into the risk of acquiring HEV in occupational exposure workers with open-air activities. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

14 pages, 624 KiB

Open AccessArticle

Hepatitis E Virus Seroprevalence and Associated Risk Factors in Apparently Healthy Individuals from Osun State, Nigeria

by Folakemi Abiodun Osundare, Patrycja Klink, Catharina Majer, Olusola Aanuoluwapo Akanbi, Bo Wang, Mirko Faber, Dominik Harms, C.-Thomas Bock and Oladele Oluyinka Opaleye

Pathogens 2020, 9(5), 392; https://doi.org/10.3390/pathogens9050392 - 20 May 2020

Cited by 5 | Viewed by 3340

Abstract

Hepatitis E virus (HEV) infection is a major public health concern in low-income countries, yet incidence and prevalence estimates are often lacking. Serum (n = 653) and faecal (n = 150) samples were collected from apparently healthy individuals using convenience sampling technique in six communities (Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo) from Osun State, Nigeria. Serum samples were analysed for total anti-HEV IgG/IgM and anti-HEV IgM using commercially available HEV ELISA kits. Total anti-HEV positive serum and all stool samples were analysed for HEV RNA by RT-PCR. Overall, 15.0% (n = 98/653) and 3.8% (n = 25/653) of the serum samples were positive for anti-HEV total and IgM antibodies, respectively. Total anti-HEV and IgM in Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo was 21.0% (n = 13/62) and 3.2% (n = 2/62), 19.4% (n = 20/103) and 6.8% (n = 7/103), 11.4% (n = 12/105) and 2.9% (n = 3/105), 8.0% (n = 16/199) and 1.5% (n = 3/199), 22.0% (n = 22/100) and 10.0% (n = 10/100), and 17.9% (n = 15/84) and 0.0% (n = 0/84), respectively. All samples (stool and serum) were HEV RNA negative. Anti-HEV seroprevalence was associated with rural location, increasing age, alcohol consumption, and rearing of animals. This study demonstrated a high anti-HEV seroprevalence in Osun State, indicating the need to implement surveillance and asses the hepatitis E burden in Nigeria. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

15 pages, 1894 KiB

Open AccessArticle

Establishment of a Plasmid-Based Reverse Genetics System for the Cell Culture-Adapted Hepatitis E Virus Genotype 3c Strain 47832c

by Johannes Scholz, Christine Bächlein, Ashish K. Gadicherla, Alexander Falkenhagen, Simon H. Tausch and Reimar Johne

Pathogens 2020, 9(3), 157; https://doi.org/10.3390/pathogens9030157 - 25 Feb 2020

Cited by 11 | Viewed by 3237

Abstract

The hepatitis E virus (HEV) causes acute and chronic hepatitis in humans. Investigation of HEV replication is hampered by the lack of broadly applicable, efficient cell culture systems and tools for site-directed mutagenesis of HEV. The cell culture-adapted genotype 3c strain 47832c, which represents a typical genotype predominantly detected in Europe, has previously been used for several basic and applied research studies. Here, a plasmid-based reverse genetics system was developed for this strain, which efficiently rescued the infectious virus without the need for in vitro RNA transcription. The cotransfection of T7 RNA polymerase-expressing BSR/T7 cells with one plasmid encoding the full-length viral genome and two helper plasmids encoding vaccinia virus capping enzymes resulted in the production of infectious HEV, which could be serially passaged on A549/D3 cells. The parental and recombinant virus exhibited similar replication kinetics. A single point mutation creating an additional restriction enzyme site could be successfully introduced into the virus genome of progeny virus, indicating that the system is suitable for site-directed mutagenesis. This system is the first plasmid-based HEV reverse genetics system, as well as the first reverse genetics system for HEV genotype 3c, and should therefore be of broad use for basic and applied HEV research. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

11 pages, 957 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Evaluation of Hepatitis E Serology and Molecular Testing in a Large Cohort

by Olympia E. Anastasiou, Viktoria Thodou, Annemarie Berger, Heiner Wedemeyer and Sandra Ciesek

Pathogens 2020, 9(2), 137; https://doi.org/10.3390/pathogens9020137 - 19 Feb 2020

Cited by 12 | Viewed by 3090

Abstract

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. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

10 pages, 1713 KiB

Open AccessArticle

Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo

by Gulce Sari, Martijn D.B. van de Garde, Anne van Schoonhoven, Jolanda J.C. Voermans, Annemiek A. van der Eijk, Robert A. de Man, Andre Boonstra, Thomas Vanwolleghem and Suzan D. Pas

Pathogens 2019, 8(4), 255; https://doi.org/10.3390/pathogens8040255 - 22 Nov 2019

Cited by 9 | Viewed by 3069

Abstract

Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

Review

Jump to: Research, Other

21 pages, 984 KiB

Open AccessEditor’s ChoiceReview

Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health

by Srinivas Reddy Pallerla, Dominik Harms, Reimar Johne, Daniel Todt, Eike Steinmann, Mathias Schemmerer, Jürgen J. Wenzel, Jörg Hofmann, James Wai Kuo Shih, Heiner Wedemeyer, C.-Thomas Bock and Thirumalaisamy P. Velavan

Pathogens 2020, 9(10), 856; https://doi.org/10.3390/pathogens9100856 - 20 Oct 2020

Cited by 61 | Viewed by 6307

Abstract

Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current view of the global circulation and epidemiology of this emerging virus. The history of HEV, from the first reported enteric non-A non-B hepatitis outbreaks, to the discovery of the viral agent and the molecular characterization of the different human pathogenic genotypes, is discussed. Furthermore, the current state of research regarding the virology of HEV is critically assessed, and the challenges towards prevention and diagnosis, as well as clinical risks of the disease described. Together, these points aim to underline the significant impact of hepatitis E on global health and the need for further in-depth research to better understand the pathophysiology and its role in the complex disease manifestations of HEV infection. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

23 pages, 1585 KiB

Open AccessEditor’s ChoiceReview

Orthohepevirus C: An Expanding Species of Emerging Hepatitis E Virus Variants

by Bo Wang, Dominik Harms, Xing-Lou Yang and C.-Thomas Bock

Pathogens 2020, 9(3), 154; https://doi.org/10.3390/pathogens9030154 - 25 Feb 2020

Cited by 39 | Viewed by 3878

Abstract

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that has received an increasing amount of attention from virologists, clinicians, veterinarians, and epidemiologists over the past decade. The host range and animal reservoirs of HEV are rapidly expanding and a plethora of emerging HEV variants have been recently identified, some of which have the potential for interspecies infection. In this review, the detection of genetically diverse HEV variants, classified into and presumably associated with the species Orthohepevirus C, currently comprising HEV genotypes C1 and C2, by either serological or molecular approach is summarized. The distribution, genomic variability, and evolution of Orthohepevirus C are analyzed. Moreover, the potential risk of cross-species infection and zoonotic transmission of Orthohepevirus C are discussed. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

Other

Jump to: Research, Review

6 pages, 1141 KiB

Open AccessCase Report

Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment

by Bernhard Schlevogt, Volker Kinast, Julia Reusch, Andrea Kerkhoff, Dimas Praditya, Daniel Todt, Hartmut H. Schmidt, Eike Steinmann and Patrick Behrendt

Pathogens 2019, 8(3), 129; https://doi.org/10.3390/pathogens8030129 - 22 Aug 2019

Cited by 6 | Viewed by 3500

Abstract

Hepatitis E virus (HEV) is an increasingly recognised pathogen, affecting several hundred thousand individuals in western countries each year. Importantly, the majority of immunocompromised individuals are not able to clear HEV but develop a chronic course of infection. In the case of lymphoma, which is an inherent immunosuppressive disease per se, chemotherapy can even further exacerbate the immunosuppressive status. As the mechanism of HEV chronification is barely understood, it is important to gain knowledge about the influence of chemotherapeutic drugs on the HEV replication cycle to guide rational clinical management of HEV infection in such patients. In this case report, a 70 year old man was diagnosed with lymphoplasmacytic lymphoma. As we observed the occurrence of chronic HEV after treatment with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in vivo, we investigated the influence of BTK signaling and ibrutinib treatment in the HEV replication cycle in vitro. First, we detected an HEV-induced mobilisation of BTK in human liver cells during HEV replication. A moderate antiviral effect against HEV replicating isolates including genotypes 1 and 3 was observed, suggesting that ibrutinib did not support HEV replication in a direct manner. Combinatory treatments of ibrutinib with ribavirin indicated that ibrutinib did not influence the antiviral effect of ribavirin. Taken together, chemotherapy targeting cellular factors for the treatment of lymphomas may be a neglected risk factor for the chronification of HEV. For ibrutinib, despite the upregulation of its target BTK during HEV replication, we observed neither a proviral effect on HEV replication nor an influence on the antiviral effect of ribavirin, suggesting that the chronification of HEV may be favoured by its immunosuppressive effect. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infections)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Hepatitis E Virus (HEV) Infections

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI