Elsevier

The Lancet

Volume 379, Issue 9835, 30 June–6 July 2012, Pages 2477-2488
The Lancet

Seminar
Hepatitis E

https://doi.org/10.1016/S0140-6736(11)61849-7Get rights and content

Summary

Hepatitis E virus (HEV) was discovered during the Soviet occupation of Afghanistan in the 1980s, after an outbreak of unexplained hepatitis at a military camp. A pooled faecal extract from affected soldiers was ingested by a member of the research team. He became sick, and the new virus (named HEV), was detected in his stool by electron microscopy. Subsequently, endemic HEV has been identified in many resource-poor countries. Globally, HEV is the most common cause of acute viral hepatitis. The virus was not initially thought to occur in developed countries, but recent reports have shown this notion to be mistaken. The aim of this Seminar is to describe recent discoveries regarding HEV, and how they have changed our understanding of its effect on human health worldwide.

Section snippets

Virus biology and evolution

Hepatitis E virus (HEV) belongs to the genus Hepevirus in the Hepeviridae family. This family contains mammalian HEV infecting human beings, domestic pigs, wild boar, deer, and rodents,1, 2 but also avian HEV3 and cut-throat trout virus,4 representing a potential separate genus. The two latter groups share about half of the nucleotide sequence of mammalian HEV strains and have not been associated with cases in human beings.3, 4

HEV is a small non-enveloped virus with a size of 27–34 nm, and has

Laboratory diagnosis of HEV infection

HEV can be diagnosed either directly by detecting its nucleic acids or indirectly by detecting an immune response in the host. The initial diagnosis is commonly made indirectly with serological techniques, because of the ease of these techniques and the short duration of viraemia.

HEV in developing countries

Epidemics of hepatitis E occur periodically throughout the developing world, and are mainly caused by HEV1 in Asia and HEV2 in Africa and Mexico (figure 2). The first, retrospectively identified outbreak of hepatitis E caused 29 300 cases in India from 1955–56.52 Other large outbreaks affecting thousands of people have occurred in China,53 India,54 Somalia,55 and Uganda.56 In addition to epidemic infection, sporadic cases of HEV occur throughout endemic regions. Infection is mainly transmitted

Chronic HEV infection

HEV3 causes chronic infection, defined by persisting HEV RNA in serum or stools for 6 months or more, in immunosuppressed patients.97, 98 Most cases have occurred in solid-organ-transplant recipients.97, 98, 99, 100, 101 Additionally, a few cases have been reported in individuals with HIV48, 102, 103 and patients with haematological disorders receiving chemotherapy.104, 105, 106 Chronic infection with HEV1 or HEV2 has not been reported.

Neurological complications

In the past 10 years HEV-associated neurological syndromes have been described in developing countries. These reports include Guillain-Barré syndrome,116 Bell's palsy,117 neuralgic amyotrophy,118 acute transverse myelitis,119 and acute menginoencephalitis.120 Few of these studies used molecular techniques to confirm the diagnosis or genotype. Since these cases mostly originate from the Indian subcontinent, HEV1 is probably the causative agent.

Recently, neurological complications were described

Acute HEV

Most cases of acute HEV infection are self-limiting and require no treatment. However, patients with or without pre-existing chronic liver disease with acute severe HEV3 infection, have been treated successfully with ribavirin monotherapy.128, 129 In developing countries, effective treatment of pregnant women with HEV1 infection is needed, but a treatment has yet to be established. Although ribavirin therapy is contraindicated in pregnancy due to teratogenicity, the risks of untreated HEV to

HEV and safety of blood products

The high rate of asymptomatic HEV infections worldwide has raised concern of infection via blood donation. Post-transfusion hepatitis E has been reported in many countries.135, 136, 137 A study of blood donors in London, UK, showed 11% of donor sera to be HEV IgG reactive and 0·7% IgM reactive.83 0·7% of plasma mini-pools from English donors contained HEV RNA.138 Similar findings have been reported in China and a global investigation into plasma fractionation pools reported that 10% of pools

HEV prevention

HEV infections could be prevented in two ways: reducing exposure to the virus and inducing immunity through vaccination. The key prevention strategy for HEV in developing countries is reducing exposure by improving the sanitary infrastructure, and providing clean drinking water. In developed countries, prevention is more complex because several possible routes of infection exist, which are not fully understood. Approaches might include ensuring that meat products are thoroughly cooked, advising

Future research

Our understanding of HEV has changed enormously over the past 30 years, from a waterborne infection causing outbreaks of acute hepatitis in developing countries to an infection of global distribution causing a range of hepatic and extra-hepatic illness. This development has been largely driven by the use of molecular techniques. However, many unanswered questions regarding HEV still remain (table 2). Before these questions can be addressed with any degree of certainty, properly standardised

Search strategy and selection criteria

We searched Medline, Current Contents, and references from relevant articles published between January, 1986, and September, 2011; many articles were identified through searches of the extensive files of the authors. Search terms were “hepatitis E”, “HEV transmission”, “HEV genotypes”, “HEV serology”, and “the discovery of HEV”.

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