Original Article
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World J Hepatol. Jun 27, 2014; 6(6): 426-434
Published online Jun 27, 2014. doi: 10.4254/wjh.v6.i6.426
Hepatitis E virus in patients with acute severe liver injury
Claire Louise Crossan, Kenneth J Simpson, Darren G Craig, Christopher Bellamy, Janice Davidson, Harry R Dalton, Linda Scobie
Claire Louise Crossan, Department of Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, United Kingdom
Kenneth J Simpson, Darren G Craig, Janice Davidson, Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom
Christopher Bellamy, Department of Pathology, University of Edinburgh, Edinburgh, EH16 4SB, United Kingdom
Harry R Dalton, Gastrointestinal Unit, Royal Cornwall Hospital, and European Centre for the Environment and Human Health, University of Exeter Medical School, Truro, TR1 3HD, United Kingdom
Linda Scobie, Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, United Kingdom
Author contributions: Crossan CL carried out the molecular and serological assays and drafted the manuscript; Simpson KJ, Dalton HR and Scobie L conceived the study and participated in its design and co-ordination, statistical analysis, funding and final reviewing of the manuscript; Craig DG and Davidson J participated in the collection and processing of the samples from the patients; Bellamy C carried out all histopathology; all authors read and approved the final manuscript.
Supported by Chief Scientist Office Scotland (under project ETM/32)
Correspondence to: Linda Scobie, PhD, Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow, G4 0BA, United Kingdom. linda.scobie@gcu.ac.uk
Telephone: +44-141-3318534 Fax: +44-141-3313208
Received: December 18, 2013
Revised: April 8, 2014
Accepted: May 29, 2014
Published online: June 27, 2014

AIM: To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit.

METHODS: Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction.

RESULTS: Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases.

CONCLUSION: In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.

Keywords: Virology, Infection, Acute liver injury, Hepatitis E virus

Core tip: Misdiagnosis of hepatitis E infection in drug induced liver injury has been noted in patients previously in South East England (13%) and the United States (3%). However, hepatitis E virus is still not given precedence when diagnosing these individuals. In our study, 5% of individuals tested were misdiagnosed and viraemic. It is an important clinical point that the diagnosis of drug induced liver injury is not secure without first excluding hepatitis E, irrespective of travel history, particularly in patients with elevated transaminases.