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Volume 17
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10.3390/v17101389
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Article

Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe

by
Ágnes Dencs
1,
Andrea Hettmann
1,
Levente Zsichla
2,3,
Viktor Müller
2,3,
Anett Dömötör
1,
Ágnes Barna-Lázár
1,
Erzsébet Barcsay
1 and
Mária Takács
1,4,*
1
National Reference Laboratory for Hepatitis Viruses, National Center for Public Health and Pharmacy, 1437 Budapest, Hungary
2
Institute of Biology, ELTE Eötvös Loránd University, 1117 Budapest, Hungary
3
National Laboratory for Health Security, ELTE Eötvös Loránd University, 1117 Budapest, Hungary
4
Institute of Medical Microbiology, Semmelweis University, 1089 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Viruses 2025, 17(10), 1389; https://doi.org/10.3390/v17101389 (registering DOI)
Submission received: 29 August 2025 / Revised: 11 October 2025 / Accepted: 17 October 2025 / Published: 18 October 2025
(This article belongs to the Section Human Virology and Viral Diseases)
Versions Notes

Abstract

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis in Europe, with increasing recognition in immunocompromised patients. While genotype 3 (HEV-3) is most prevalent in the region, molecular epidemiology data from Hungary have been limited. HEV strains from 118 RNA-positive patients diagnosed between 2018 and 2025 were genotyped. Next-generation sequencing yielded near-complete HEV genomes for 76 samples. HEV-3 was dominant (98.3%). Subtype 3a was the most common (34.7%), followed by 3c, 3f, and 3e. Rare subtypes (3g, 3h, 3i, 3m, 3ra) and HEV-4b were detected for the first time in Hungary. Among immunocompromised patients, 41.6% developed chronic infection. Ribavirin resistance-associated mutations G1634R and V1479I were frequently detected. In silico analysis of potential multiple infections indicated the presence of at least two HEV strains of distinct origin in six patients. Our surveillance revealed extensive genetic diversity of HEV in Hungary. The detection of rare HEV-3 subtypes and the first documented occurrence of HEV-4b in the country highlight likely viral introductions linked to the increasing international trade. Ongoing surveillance is essential in protecting high-risk groups and limiting HEV transmission in a globalized food system.
Keywords: hepatitis E virus; molecular epidemiology; molecular surveillance; genotype; subtype; sequencing; phylogenetic analysis; virus strain hepatitis E virus; molecular epidemiology; molecular surveillance; genotype; subtype; sequencing; phylogenetic analysis; virus strain

Share and Cite

MDPI and ACS Style

Dencs, Á.; Hettmann, A.; Zsichla, L.; Müller, V.; Dömötör, A.; Barna-Lázár, Á.; Barcsay, E.; Takács, M. Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe. Viruses 2025, 17, 1389. https://doi.org/10.3390/v17101389

AMA Style

Dencs Á, Hettmann A, Zsichla L, Müller V, Dömötör A, Barna-Lázár Á, Barcsay E, Takács M. Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe. Viruses. 2025; 17(10):1389. https://doi.org/10.3390/v17101389

Chicago/Turabian Style

Dencs, Ágnes, Andrea Hettmann, Levente Zsichla, Viktor Müller, Anett Dömötör, Ágnes Barna-Lázár, Erzsébet Barcsay, and Mária Takács. 2025. "Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe" Viruses 17, no. 10: 1389. https://doi.org/10.3390/v17101389

APA Style

Dencs, Á., Hettmann, A., Zsichla, L., Müller, V., Dömötör, A., Barna-Lázár, Á., Barcsay, E., & Takács, M. (2025). Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe. Viruses, 17(10), 1389. https://doi.org/10.3390/v17101389

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