An Evaluation of Hepatitis E Virus Molecular Typing Methods

Sally A. Baylis*, Cornelia Adlhoch, Liam Childs, Anett Stühler, Marie Karlsson, Michel Molier, Vanessa Suin, Sophie Lamoral, Neda Nasheri, Jennifer Harlow, Irina Rešetnjak, Florence Abravanel, Sebastien Lhomme, Jacques Izopet, Nicole Pavio, Marie Pellerin, Martin Eiden, Birke Boettcher, Marco Kaiser, Katja Schilling-loefflerReimar Johne, Tatjana Schwarz, Victor M. Corman, Jürgen J. Wenzel, Jasmin Klein, Charlene Bennett, Cillian Degascun, Jonathan Dean, Anna Rita Ciccaglione, Umbertina Villano, Roberto Bruni, Ilaria Di Bartolo, Luca De Sabato, Giuseppina La Rosa, Giusy Bonanno Ferraro, Pamela Mancini, Elisabetta Suffredini, Anna Rosa Garbuglia, Ingeborg Boxman, René Dirks, Ans Zwartkruis-nahuis, Boris Hogema, Rita De Sousa, Branko Velebit, Ana Avellón, Gloria Sánchez, Enric Cuevas-ferrando, Heléne Norder, Claudia Bachofen, Isabelle Vonlanthen, Jakub Kubacki, David Lacher, Mark Mammel, Michael Kulka

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Better understanding of HEV subtypes involved in hepatitis E infections is essential. Investigation of sources and routes of transmission and the identification of potential clusters/outbreaks rely upon molecular typing of viral strains. A study was carried out to evaluate the ability of laboratories to undertake molecular typing with genotype and subtype determination.
A blinded panel of 11 different Orthohepevirus A strains was distributed to 28 laboratories performing HEV sequence analysis. Laboratories used their routine HEV sequencing and genotyping methods.
Results were returned by 25 laboratories. Overall, 93% samples were assigned to the correct genotype and 81% were assigned to the correct subtype. Fragments amplified for typing ranged in size and the sequencing assays targeted both the structural and non-structural protein-coding regions. There was good agreement between the reported sequences where methods targeted overlapping fragments. In some cases, incorrect genotypes/subtypes were reported, including those not contained in the panel, and in one case, a genotype was reported for a blinded control sample containing Zika virus; collectively these data indicate contamination problems.
In general, identification of genotypes was good; however, in a small number of cases, there was a failure to generate sequences from some of the samples. There was generally broad agreement between the use of online typing tools such as the one provided by HEVnet and curated lists of published HEV reference sequences; however, going forward harmonization between these resources is essential.
Original languageEnglish
Pages (from-to)181-191
JournalClinical Chemistry
Issue number1
Publication statusPublished - 30 Dec 2021


  • genotype
  • hepatitis E virus
  • HEV
  • sequencing
  • subtype


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