Paul-Ehrlich-Institut

Evaluation of Molecular Hepatitis E Typing – Good Performance from International Reference Labs

02 / 2022

Infections with the hepatitis E virus (HEV) are one of the main causes of acute viral hepatitis worldwide. An international team of experts headed up by the Paul-Ehrlich-Institut investigated the question of how reliably HEV reference laboratories in Europe and North America can carry out HEV molecular typing. Twenty-five labs took part in the study, during which 93% of the samples were assigned to the correct genotype and 81% to the correct subtype. At the same time, gaps and deficiencies in individual laboratories as well as potential areas for method optimisation were identified. Clinical Chemistry reported on the results in its online edition from 30 December 2021.

Model Hepatitis E Virus (Source: Kateryna Kon/Shutterstock.com)

Hepatitis E virus (HEV) infections are one of the leading causes of acute viral hepatitis (inflammation of the liver) worldwide. HEV belongs to the Hepeviridae virus family, genus Orthohepevirus (species A to D), which can infect many different hosts, such as mammals (humans included), birds, and fish. The vast majority of human hepatitis E cases are caused by strains within species A, which in turn comprises 8 genotypes and 36 subtypes. The subtypes are diverse and are updated as new subtypes are identified. Genotypes 1 and 2 only infect humans, are spread by the faecal-oral route, and pose a particular risk for pregnant women. They do not play any role in Europe, however. In contrast, HEV genotypes 3 and 4 cause infections in animal species such as pigs and wild boars and can cause zoonotic infections in humans. These infections are primarily driven through the consumption of contaminated meat and meat products, such as sausage. Genotype 3 HEV, the main cause of hepatitis E infections in Europe, is particularly diverse at the molecular level.

The consequences of HEV infection can be particularly severe for people with underlying liver disease. Chronic infection with HEV is a problem, especially for those with compromised immune systems (immunosuppression), which is almost exclusively caused by HEV genotype 3.

The European Centre for Disease Prevention and Control (ECDC) hepatitis E working group has developed a framework for hepatitis E surveillance in the European Union/European Economic Area (EU/EEA). The group's focus is on epidemiology – i.e., research into the origin, spread, impact, and control of acute and chronic infections. In order to be able to examine and monitor the various HEV subtypes and their importance in the course of infection and illness, the unambiguous identification of the HEV subtypes involved in hepatitis E infections is necessary.

Experts from the Paul-Ehrlich-Institut, led by Dr Sally Baylis and Dr Liam Childs, together with the ECDC under the direction of Dr Cornelia Adlhoch, initiated a study to examine the reliability of hepatitis E typing in various laboratories in different countries. The study, coordinated by the Paul-Ehrlich-Institut, was carried out with experts from the ECDC as well as the HEV working group and HEVnet, a global network of scientists from hepatitis E reference laboratories. The aim was to assess the overall performance of molecular typing of HEV strains. HEV reference laboratories from EU/EEA member states and HEVnet were among the labs eligible to participate in the study. A total of 25 laboratories took part.

In the study, 93% of the samples were assigned to the correct genotype and 81% to the correct subtype. However, in some cases incorrect genotypes/subtypes were also reported. Overall, the data indicated contamination problems. The reference laboratories performed well as a whole in this first practical study evaluating the performance of various HEV sequencing methods. However, gaps or methodological deficiencies were identified – in areas such as contamination control, for example. The identified gaps could be used by the individual laboratories to improve performance standards.

Further harmonisation and optimisation of methods is important to improve efforts to monitor imported and endemic HEV strains.

Original Publication

Baylis SA, Adlhoch C, Childs L, and the HEV Sequencing Study Group (2022): An Evaluation of Hepatitis E Virus Molecular Typing Methods.
Clin Chem 68: 181-191.
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Updated: 20.01.2022