HEV in wastewater relevant to clinical variants





The hepatitis E virus (HEV) is spread worldwide and can, under certain circumstances, lead to severe acute and chronic courses of illness. Treatment with antivirals can cause variants that lead to resistance to therapy. The frequency of these variants remains unknown in the human population as well as environment due to limited comprehensive data on HEV diversity.

A recent  study led by Dr. Daniel Todt from Ruhr University Bochum, Germany, investigated the HEV prevalence and diversity of circulating variants in environmental samples, that is, wastewater of 21 wastewater treatment plants and water of two rivers from North-Rhine Westphalia, Germany. Between March 2020 and March 2021 in total 605 samples were collected. Approximately 73% of all samples were tested positive for HEV RNA via qPCR, and in river water 78.57% were positive. The team were able to demonstrate that the proportion of HEV-RNA positive samples was reduced by almost a quarter on average after wastewater treatment (HEV RNA positiv rates: influent water 79.17%; effluent water 54.55%). They assessed viral diversity of eight samples relative to the sample-specific consensus sequence. Some of the analyzed samples showed a greater heterogeneity of single nucleotide variants (SNVs) than others. In addition, they analyzed the samples for the presence of subtypes linked to increased pathogenicity and variants associated with treatment failure. Phylogenetic analysis revealed that all wastewater sequences cluster with HEV-3 reference strains and were closely related to HEV-3c.

Water-based epidemiology can show the circulation of pathogens in a population. Many viruses have previously been found in wastewater. There is a large number of pig livestock in North-Rhine Westphalia, it is likely that this contributes to the high levels of HEV-RNA in local wastewater. These data suggest that active infections are common in humans and animals. However, it is not possible to distinguish between human and porcine infections in this zoonotic genotype. HEV-3 is the dominant infection-causing genotype in western countries; this genotype, predominantly subtype c, was also dominantly represented in wastewater in other European studies. HEV-3 clade egf has been associated with more severe clinical outcomes, these specific clades were not detected in this study. However, increased heterogeneity was present at Position 1479, which had been detected in chronically infected patients who did not respond to RBV or SOF treatment. Other studies similarly showed reduced viral load in effluent water compared to influent  water.

Overall, this study demonstrated that wastewater surveillance can contribute to HEV surveillance for new variants and those with clinical significance.

Read the full article: Liver International. 2024 Jan 30. DOI: 10.1111/liv.15842

The featured image was provided by Fiona Rau.


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