scholarly journals Hepatitis E Virus Immunopathogenesis

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1180
Author(s):  
Kush Kumar Yadav ◽  
Scott P. Kenney
Keyword(s):  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Oral Route ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
In Vivo Models ◽  
Transplant Patients

Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.

scholarly journals Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

2012 ◽  
Vol 86 (18) ◽  
pp. 10006-10014 ◽  
Author(s):  
Sebastien Lhomme ◽  
Florence Abravanel ◽  
Martine Dubois ◽  
Karine Sandres-Saune ◽  
Lionel Rostaing ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Serum Concentrations

Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lowerKa/Ksratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

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

2015 ◽  
Vol 60 (3) ◽  
pp. 1608-1614 ◽  
Author(s):  
Sebastien Lhomme ◽  
Nassim Kamar ◽  
Florence Nicot ◽  
Jacques Ducos ◽  
Michael Bismuth ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Virologic Response ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Viral Response ◽  
Transplant Patients ◽  
Initial Decrease

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

scholarly journals Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 630 ◽  
Author(s):  
Sebastien Lhomme ◽  
Swati DebRoy ◽  
Nassim Kamar ◽  
Florence Abravanel ◽  
David Metsu ◽  
...  
Keyword(s):  
Partial Response ◽  
Half Life ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
Response To Therapy ◽  
Solid Organ ◽  
Transplant Patients ◽  
Viral Kinetic

Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0–21) days, plasma HEV declined from a median baseline level of 6.12 (3.53–7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)–(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response.

Hepatitis E Virus and the Kidney in Solid-Organ Transplant Patients

2012 ◽  
Vol 93 (6) ◽  
pp. 617-623 ◽  
Author(s):  
Nassim Kamar ◽  
Hugo Weclawiak ◽  
Céline Guilbeau-Frugier ◽  
Florence Legrand-Abravanel ◽  
Olivier Cointault ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Patients

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

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 255 ◽  
Author(s):  
Gulce Sari ◽  
Martijn D.B. van de Garde ◽  
Anne van Schoonhoven ◽  
Jolanda J.C. Voermans ◽  
Annemiek A. van der Eijk ◽  
...  
Keyword(s):  
Amino Acids ◽  
Hepatitis E Virus ◽  
A549 Cells ◽  
Hepatitis E ◽  
Solid Organ ◽  
Genotype 3 ◽  
Humanized Mouse ◽  
Genomic Alterations

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.

Loss of Anti-Hepatitis E Virus Antibodies in Organ Transplant Patients with Hepatitis E

2020 ◽  
Author(s):  
Yukio Oshiro ◽  
Hiroshi Harada ◽  
Kiyoshi Hasegawa ◽  
Naotake Akutsu ◽  
Tomoharu Yoshizumi ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Transplant Patients

scholarly journals Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands

2012 ◽  
Vol 18 (5) ◽  
pp. 869-872 ◽  
Author(s):  
Suzan D. Pas ◽  
Rob A. de Man ◽  
Claudia Mulders ◽  
Aggie H.M.M. Balk ◽  
Peter T.W. van Hal ◽  
...  
Keyword(s):  
Virus Infection ◽  
The Netherlands ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients
Sign in / Sign up

Export Citation Format

Share Document