Review Article

Hepatitis E—A Concise Review of Virology, Epidemiology, Clinical Presentation and Therapy

M. C. Donnelly; L. Scobie; C. L. Crossan; H. Dalton; P. C. Hayes; K. J. Simpson


Aliment Pharmacol Ther. 2017;46(2):126-141. 

In This Article

Diagnostic Mimicry

As HEV infection (both acute and chronic) is clinically indistinguishable from other causes of hepatitis, it is likely that HEV infection is under-diagnosed. The relevance of autochthonous HEV infection is only recently recognised, and it is likely that patients who have presented with severe acute liver injury/acute liver failure due to HEV in the past have been mislabelled as having an alternative diagnosis. As such, several centres have retrospectively analysed stored sera from patients with indeterminate acute liver failure (ie, non A to E hepatitis, seronegative hepatitis) for presence of HEV. One German group retrospectively analysed stored sera from patients with 'indeterminate acute liver failure' for anti-HEV IgM, IgG and HEV RNA.[119] 10% of samples tested positive for HEV RNA and had clinical findings which would support the diagnosis of acute HEV infection. In Scotland, 80 patients with severe acute liver injury were tested for serological markers of HEV infection.[120] Three patients tested positive for anti-HEV IgG, anti-HEV IgM and HEV RNA. One further patient tested anti-HEV IgG and IgM positive, but HEV RNA negative. The patient with negative HEV RNA testing had been initially diagnosed as having acute liver failure secondary to a paracetamol overdose. Of the other patients, one was initially diagnosed as having a drug induced liver injury, another had travel-acquired HEV infection and the remainder was found to have liver cirrhosis on further investigation, presenting with decompensated disease secondary to HEV. In addition, patients previously having been labelled as having drug induced liver injury are increasingly recognised to in fact have had acute HEV infection. In a UK study of patients with drug induced liver injury, on retrospective testing 13% were found to have autochthonous HEV infection.[121] Smaller numbers have been reported from the USA —3% of patients with suspected drug induced liver injury retrospectively tested positive for anti-HEV IgM.[122] In patients undergoing allogeneic haematopoietic stem cell transplant, graft-versus-host disease may present with clinical features similar to HEV infection. In one study of stem cell transplant recipients, 2.4% of 328 patients developed HEV infection, in which the pattern of liver function test abnormality was indistinguishable from that of graft-versus-host disease.[110] This is clearly an important clinical distinction to make as the two conditions are treated entirely differently in terms of adjustments of immunosuppression.