Molecular epidemiology and genotype-specific disease severity of hepatitis E virus infections in Germany, 2010–2019

Abstract

Zoonotic hepatitis E virus (HEV) is endemic in Europe. Genotype 3 (HEV-3) is predominant but information on subtype distribution, trends and clinical implications in Germany is scarce. We analysed 936 HEV RNA positive samples of human origin and corresponding national surveillance data from 2010 to 2019. Samples were referred to the National Consultant Laboratory and sequenced in at least one of four genomic regions. Sequences were analysed using bioinformatics methods and compared to the latest HEV reference set. 1,656 sequences were obtained from 300 female, 611 male and 25 of unknown sex aged 3–92 years (median 55 years). HEV-3c was predominant (67.3%) followed by HEV-3f, HEV-3e and HEV-3i(-like) with 14.3%, 9.7% and 4.0% (other subtypes ≤1.1%). The proportion of HEV-3 group 2 (3abchijklm) strains increased over time. Jaundice, upper abdominal pain, fever, hospitalization, and death due to HEV were significantly more often reported for patients infected with HEV-3 group 1 (3efg) compared to group 2. Larger spatio-temporal clusters of identical sequences were not observed. HEV-3 group 1 infections are more severe as compared to the predominant group 2. Detection of group 2 strains increased over the last years, possibly due to more frequent diagnosis of asymptomatic and mild courses. The diversity of strains and the space–time distribution is compatible with a foodborne zoonosis with supra-regional distribution of the infection vehicle (pork products).

Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms

“…In addition, both HEV X domain and polyproline region heterogeneity were proposed as being associated with viral persistence ( Lhomme et al, 2014 ). Interestingly, our results show that the HEV-3 X domain has several polymorphic amino acids that are associated with clades, an observation that might be consistent with the recently reported clade differences in clinical behavior ( Schemmerer et al, 2022 ). Additionally, it has recently been suggested that the conserved macrodomain is a potential therapeutic target for coronavirus and alphavirus ( Leung et al, 2022 ).…”

Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7‐day storage

“…Increased HEV prevalence in farm animals and wildlife has been reported in France and other European countries since 2015. Rising HEV incidence has also been documented in blood donors and the general population 39–42 …”

“…Rising HEV incidence has also been documented in blood donors and the general population. [39][40][41][42] No cases of TA-GVHD, a potentially fatal reaction associated with donor leucocytes, were reported for any PCs in any period.…”

Geographic and Temporal Variability of Hepatitis E Virus Circulation in the Russian Federation

“…HEV genotypes 1 to 4 are further divided into numerous sub-genotypes, with the HEV genotype 3 (HEV-3) sub-genotypes grouped into three monophyletic clades: clade 1 (3e, f, and g), clade 2 (a, b, c, h, i, j, k, l, and m), and HEV-3ra (rabbit) [ 3 ]. Interestingly, the strains from HEV-3 clade 1 were reported to be associated with more severe disease in humans compared with the HEV-3 group 2 strains [ 7 ]. Given its large territory, the Russian Federation is bordered by both non-endemic European countries where HEV-3 is tightly controlled [ 8 ], and endemic territories, such as the Central Asian countries and China, where both the zoonotic genotypes 3 and 4, as well as the anthroponotic genotype 1, are prevalent [ 9 , 10 ].…”