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. 2025 Apr;53(2):523-534.
doi: 10.1007/s15010-024-02348-0. Epub 2024 Sep 10.

HEV-3 subtypes and strains detected in cases of HEV infection in central Italy from 2015 to 2023

Anna Rosa Garbuglia  1 , Gjergji Koja  2   3 , Umbertina Villano  4 , Claudia Minosse  1 , Michele Equestre  5 , Silvia Pauciullo  1 , Antonio Coppola  1 , Elisabetta Madonna  4 , Giovanna Picchi  6   7 , Jessica Di Biase  8 , Margherita Dalessandro  8 , Anna Rughetti  9 , Katia Casinelli  10 , Barbara Camilloni  11 , Rinalda Mariani  8 , Alessandro Grimaldi  6 , Anna Rita Ciccaglione  4 , Roberto Bruni  12
Affiliations

HEV-3 subtypes and strains detected in cases of HEV infection in central Italy from 2015 to 2023

Anna Rosa Garbuglia et al. Infection. 2025 Apr.

Abstract

Purpose: HEV is an emerging pathogen in Europe and was previously shown to be hyperendemic in areas of Abruzzo and Lazio, Central Italy. No systematic analysis of the HEV strains responsible for human infections over several years in Central Italy has previously been reported. Aim of the study was the molecular characterization of HEV from autochthonous hepatitis E cases occurred in Abruzzo and Lazio between 2015 and 2023.

Methods: Samples from 118 cases collected as part of virological surveillance in Abruzzo and Lazio from 2015 to 2023 were subjected to HEV sequencing and phylogenetic analysis.

Results: The main observed subtype was 3f, followed by 3c and 3e. The annual subtype distribution was quite stable over the observation period, but 3f cases tended to concentrate in winter/early spring whereas 3e cases in summer. Phylogenetic clusters of highly related sequences (a) highlighted unrecognized "point source outbreaks", (b) provided molecular support to temporally and/or geographically linked cases and (c) provided evidence for transmission of identical/highly related strains up to months/years following their first detection.

Conclusions: The data provide an overview of the HEV strains responsible for human infections over eight years in Central Italy. The observed subtype distribution appears to agree better with the subtype distribution reported in Italy in pigs rather than in geographically matched wild boars, suggesting pig and its derivate food was a more frequent source of infection than wild boar in Abruzzo and Lazio. Molecular characterization is essential to recognize "point source outbreaks" and to monitor HEV circulation.

Keywords: Foodborne diseases; Hepatitis E Virus; Phylogenetic analysis; Zoonoses.

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Conflict of interest statement

Declarations. Ethical approval: This study was approved by INMI L Spallanzani Istituto di ricovero e cura a carattere scientifico (IRCCS) Hospital Ethics Committee (agreement 29/2013, approved on 05-21-2013). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Monthly distribution of cases observed in the period 2015–2023, in which cases from a HEV outbreak occurred in Central Italy in 2019 are highlighted (orange end of the bars)
Fig. 2
Fig. 2
Phylogenetic trees for HEV subtyping, obtained by the Maximum Likelihood approach. (A) Analysis of n = 52 sequences, size 493 nt. (B) Analysis of n = 66 sequences, size 411 nt. Both trees include 39 Reference sequences representing subtypes 3a to 3 m, as reported in Smith et al., 2020 [2]. The meaning of the red and black dots is reported in the insert in the lower right corner of the figure
Fig. 3
Fig. 3
(A) Subtype distribution, HEV infection cases (n = 118) from Abruzzo and Lazio, 2015–2023. (B) Annual trend of subtype distribution of 3f, 3e and 3c cases from Abruzzo and Lazio, 2015–2023. The annual number of cases in the years 2015, 2020, 2021, 2022 was not large enough (n = 3, n = 7, n = 7 and n = 3, respectively) to give rise to a reliable annual distribution. Thus, cases from 2015 were joined to 2016, cases from 2020 were joined to 2021 and cases from 2022 were joined to 2023. (C) Monthly distribution of 3f, 3e and 3c subtype cases cumulatively observed in the period 2015–2023 in Abruzzo and Lazio, including 3f and 3e cases from the 2019 outbreak. (D) Monthly distribution of 3f, 3e and 3c subtype cases after exclusion of the 3f and 3e cases from the 2019 outbreak
Fig. 4
Fig. 4
Phylogenetic tree resulting from analysis of a 370 nt region shared by the HEV sequences obtained with different protocols (n = 118). A Maximum Likelihood approach was applied, with a GTR + G + I evolutionary model preliminarily estimated by the Model tool in MEGA. The tree includes reference sequences (n = 39) representing subtypes 3a to 3 m, as reported in in Smith et al., 2020 [2]. The meaning of red, blue and black circles is described in the box. Clusters are delimited by red lines and marked by alphabetical letters, A to N
See this image and copyright information in PMC

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