Hepatitis E virus in acute liver failure: An unusual suspect?

Sayed, Ibrahim M.; Vercouter, Ann-Sofie; Meuleman, Philip

doi:10.1002/hep.28759

Cited by 11 publications

(13 citation statements)

References 12 publications

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“…36,37 Similar to humans, NHPs and pigs, the HEV load was higher in the mouse fecal preparation than in the plasma of the same mouse at the same time point, indicating that HEV was preferentially secreted via the feces. [60][61][62][63][64] In addition, HEV RNA was detected in the mouse stool earlier than in the mouse plasma of humanized mice in a similar manner as in HEV infected chimpenzees. 35,36,62 Contrary to the mouse feces, mouse plasma had higher levels of ORF2 Ag than HEV RNA, while at the corresponding time points the relative level of viral RNA in fecal suspensions was higher than the amount of ORF2 Ag ( Figure 1).…”

Section: Human Liver Chimeric Mice (Humanized Mice)mentioning

confidence: 94%

“…Similarly, higher HEV Ag levels were detected in chronically HEV infected patients compared with acutely infected ones . HEV Ag was absent in non‐viremic mice that exhibited low‐level fecal viral load, showing that qPCR analysis on stool samples should be the gold‐standard diagnostic methodology, especially when a low‐level viral load is anticipated and where seroconversion could be absent and/or delayed as in immunocompromised patients …”

Section: Kinetics Of Hev Orf2 Ag During the Course Of Hev Infection Amentioning

confidence: 98%

“… Since the adaptive cellular immune response is lacking in these mice, antibodies against HEV cannot be formed, while bilirubin and liver transaminases such as alanine transaminase (ALT) and aspartate transaminase (AST) were not elevated in infected mice . Similar to humans, NHPs and pigs, the HEV load was higher in the mouse fecal preparation than in the plasma of the same mouse at the same time point, indicating that HEV was preferentially secreted via the feces . In addition, HEV RNA was detected in the mouse stool earlier than in the mouse plasma of humanized mice in a similar manner as in HEV infected chimpenzees .…”

Section: Course Of Hev Infection In Humanized Micementioning

confidence: 99%

“…93 HEV Ag was absent in non-viremic mice that exhibited low-level fecal viral load, showing that qPCR analysis on stool samples should be the gold-standard diagnostic methodology, especially when a low-level viral load is anticipated and where seroconversion could be absent and/or delayed as in immunocompromised patients. 59,61 Analysis of the plasma of humanized mice showed that the noninfectious glycosylated form of ORF2 (ORF2; Mr 90,000) protein was the major ORF2 form detected in mouse plasma. 59 Likewise, HEV…”

Section: Kinetics Of Hev Orf2 Ag During the Course Of Hev Infectionmentioning

confidence: 99%

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Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice

Sayed

Meuleman

2019

Reviews in Medical Virology

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Summary Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally, and it is an emerging pathogen in developed countries. In vivo studies of HEV have long been hindered due to the lack of an efficient small animal model. Recently, human liver chimeric mice were described as an elegant model to study chronic HEV infection. HEV infection was established in mice with humanized liver that were challenged with stool preparations containing HEV genotype (gt)1 and/or gt3. An increase in viral load and the level of HEV Ag in mouse samples were markers of active infection. Plasma‐derived HEV preparations were less infectious. The kinetics of HEV ORF2 Ag during HEV infection and its impact on HEV diagnosis were described in this model. In addition, the nature of HEV particles and HEV ORF2 Ag were characterized. Moreover, humanized mice were used to study the impact of HEV infection on the hepatic innate transcriptome and evaluation of anti‐HEV therapies. This review highlights recent advances in the HEV field gathered from well‐established experimental mouse models, with an emphasis on this model as a tool for elucidating the course of HEV infection, the study of the HEV life cycle, the interaction of the virus with the host, and the evaluation of new anti‐HEV therapies.

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Section: Human Liver Chimeric Mice (Humanized Mice)mentioning

confidence: 94%

Section: Kinetics Of Hev Orf2 Ag During the Course Of Hev Infection Amentioning

confidence: 98%

Section: Course Of Hev Infection In Humanized Micementioning

confidence: 99%

Section: Kinetics Of Hev Orf2 Ag During the Course Of Hev Infectionmentioning

confidence: 99%

See 2 more Smart Citations

Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice

Sayed

Meuleman

2019

Reviews in Medical Virology

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“…The main acute aetiologies of A(C)LF are hepatitis viral infection, alcoholic consumption and drug toxicity . Yet, the causes of up to 20% of A(C)LF cases remain unknown . In the past decade, Hepatitis E virus (HEV) infection is increasingly reported to be a common acute event for A(C)LF.…”

Section: Introductionmentioning

confidence: 99%

Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case‐control study

Wang¹,

Liu³

et al. 2019

Liver International

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Background/Aims: Hepatitis E virus (HEV) infection has been recognized an important insult of acute or acute-on-chronic liver failure (A(C)LF). This study aimed to identify the incidence, predictors and outcomes of A(C)LF in patients with hepatitis E. Methods:All patients diagnosed of hepatitis E between 2012 and 2018 in the tertiary hospital were retrospectively and consecutively analysed. Patients with hepatitis E who developed A(C)LF were enrolled as cases (HEV-LF) and controls were randomly selected from those who did not develop liver failure with 1:3 ratio in the same cohort.Results: Eight hundred and nine patients were diagnosed with hepatitis E, among which 80 were identified with HEV-related liver failure (HEV-LF) with HEV as the solely acute aetiology of A(C)LF. Sequencing of HEV genome showed genotype (GT) 4 strains in all available serum samples. Hepatitis E patients with cirrhosis underwent higher risk to develop liver failure, compared to non-cirrhotic patients.Hydrothorax, respiratory infections, lower γ-glutamyl transferase, higher lactate dehydrogenase and alpha-foetoprotein were found to be independent predictors of A(C)LF in patients with hepatitis E. The 28-day and 90-day mortality for HEV-LF was 12.86% and 30.36% respectively. Renal injury and lower triglyceride were independent factors associated with 28-day mortality. Lower alanine aminotransferase and higher International normalized ratio were independent predictors of 90-day mortality.

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Evaluation of hepatitis E antigen kinetics and its diagnostic utility for prediction of the outcomes of hepatitis E virus genotype 1 infection

et al. 2021

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HEV-Ag ELISA assay is a reliable diagnostic test in resource-limited areas. HEV genotype 1 (HEV-1) infections are either self-limited or progress to fulminant hepatic failure (FHF) and death if anti-HEV therapy is delayed. Limited data is available about the diagnostic utility of HEV Ag on HEV-1 infections. Herein wWe aimed to study the kinetics of HEV Ag during HEV-1 infections at different stages, i.e., acute HEV infection, recovery, and progression to FHF. Also, we evaluated the diagnostic utility of this marker to predict the outcomes of HEV-1 infections. Plasma of acute hepatitis E (AHE) patients were assessed for HEV RNA by RT-qPCR, HEV Ag, and anti-HEV IgM by ELISA. The kinetics of HEV Ag was monitored at different time points; acute phase of infection, recovery, FHF stage, and post-recovery. Our results showed that the level of HEV Ag was elevated in AHE patients with a significantly higher level in FHF patients than recovered patients. We identified a plasma HEV Ag threshold that can differentiate between self-limiting infection and FHF progression with 100% sensitivity and 88.89% specificity. HEV Ag and HEV RNA have similar kinetics during the acute phase and self-limiting infection. In the FHF stage, HEV Ag and anti-HEV IgM have similar patterns of kinetics which could be the cause of liver damage. In conclusion, the HEV Ag assay can be used as a biomarker for predicting the consequences of HEV-1 infections which could be diagnostically useful for taking the appropriate measures to reduce the complications, especially for high-risk groups.

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Hepatitis E virus in acute liver failure: An unusual suspect?

Cited by 11 publications

References 12 publications

Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice

Updates in Hepatitis E virus (HEV) field; lessons learned from human liver chimeric mice

Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case‐control study

Evaluation of hepatitis E antigen kinetics and its diagnostic utility for prediction of the outcomes of hepatitis E virus genotype 1 infection

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