Model systems for studying extrahepatic pathogenesis of hepatitis E virus. Current knowledge and future directions

El‐Mokhtar, Mohamed A.; Sayed, Ibrahim M.

doi:10.1002/rmv.2218

Cited by 12 publications

(12 citation statements)

References 154 publications

(255 reference statements)

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“…Further studies need to assess the diagnostic level of HEV Ag to predict the outcomes of HEV-1 infection in pregnant women. Likewise, extrahepatic manifestations are associated with HEV infection [44,53,54,55,56,57], this diagnostic assay could be also beneficial to predict the possibility of extrahepatic disorders associated with HEV infection.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Similar to Vero cells, MA-104s can support HAstV replication as well [ 41 ]. These cell lines are also used for the study of enteric RNA viruses causing extraintestinal disease including HAV and HEV [ 135 , 136 , 137 ].…”

Section: In Vitro Tools To Study Human Enteric Rna Virusesmentioning

confidence: 99%

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Aggarwal

Hassan

Baldridge

2021

Viruses

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Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different in vitro and in vivo tools available to explore different pathophysiological attributes of human enteric RNA viruses, highlighting their advantages and limitations depending upon the question being explored. In addition, we discuss key areas and opportunities that would benefit from further methodological progress.

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“…Chronic HEV infection is developed in immunocompromised patients such as those with HIV, leukemic individuals, and organ transplant recipients, which can lead to liver cirrhosis (Kamar et al, 2008;Riveiro-Barciela et al, 2014). Besides that, extrahepatic disorders were documented with HEV infections, such as renal, neurological, hematological, and pregnancy-related complications (Pischke et al, 2017;El-Mokhtar and Sayed, 2021). Interferon or ribavirin are used off-label in the treatment of severe and chronic HEV infection (Kamar et al, 2014;Péron et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting

et al. 2021

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Background: Currently, there are no specific biomarkers for drug-induced liver injury (DILI), and the diagnosis of DILI is based mainly on the exclusion of other causes of liver dysfunction and the recognition of potential causative drugs. Hepatitis E virus (HEV) diagnosis is not routinely enrolled in many countries, and HEV infection could be misdiagnosed as DILI.Methodology: We retrospectively analyzed plasma samples (n = 80) collected from suspected DILI for HEV markers such as anti-HEV IgM, anti-HEV IgG, and HEV RNA. Anti-HEV antibodies were assessed using commercial ELISA kits. HEV RNA was tested by RT-qPCR targeting HEV ORF2/3, the receiver operating characteristic (ROC) curve was plotted, and a putative threshold for liver function parameters was determined.Results: Out of 80 samples, 12 samples were positive for anti-HEV IgM and anti-HEV IgG, and HEV RNA was detected in seven samples. The median viral load was 3.46 × 103 IU/ml, and the isolated viruses belonged to HEV genotype 1. The level of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST), but not alkaline phosphatase (ALP), was significantly higher in HEV confirmed cases than in non-HEV confirmed cases. We identified a plasma ALT level of at least 415.5 U/L and AST level of at least 332 U/L; ALT/ALP ratio of at least 5.08 could be used as a guide for the patients diagnosed as DILI to be tested for HEV infection. The previous liver function parameters showed high sensitivity and good specificity.Conclusion: Hepatitis E virus was detected in suspected DILI cases. The diagnosis of DILI is not secure until HEV testing is done. Liver function parameters can be used as a guide for HEV testing in suspected DILI cases in countries with limited resources.

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Model systems for studying extrahepatic pathogenesis of hepatitis E virus. Current knowledge and future directions

Cited by 12 publications

References 154 publications

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

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

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting

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