Nine-Year Nationwide Environmental Surveillance of Hepatitis E Virus in Urban Wastewaters in Italy (2011–2019)

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis worldwide. To provide insights into the epidemiology of HEV in Italy, a large-scale investigation was conducted into urban sewage over nine years (2011–2019), collecting 1374 sewage samples from 48 wastewater treatment plants located in all the 20 regions of Italy. Broadly reactive primers targeting the ORF1 and ORF2 regions were used for the detection and typing of HEV, followed by Sanger and next generation sequencing (NGS). Real-time RT-qPCR was also used to attempt quantification of positive samples. HEV RNA detection occurred in 74 urban sewage samples (5.4%), with a statistically significant higher frequency (7.1%) in central Italy. Fifty-six samples were characterized as G3 strains and 18 as G1. While the detection of G3 strains occurred in all the surveillance period, G1 strains were mainly detected in 2011–2012, and never in 2017–2019. Typing was achieved in 2 samples (3f subtype). Viral concentrations in quantifiable samples ranged from 1.2 × 103 g.c./L to 2.8 × 104 g.c./L. Our results suggest the considerable circulation of the virus in the Italian population, despite a relatively small number of notified cases, a higher occurrence in central Italy, and a noteworthy predominance of G3 strains.

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Hepatitis E in Italy: 5 years of national epidemiological, virological and environmental surveillance, 2012 to 2016

Eurosurveillance ◽

10.2807/1560-7917.es.2018.23.41.1700517 ◽

2018 ◽

Vol 23 (41) ◽

Cited By ~ 12

Author(s):

Valeria Alfonsi ◽

Luisa Romanò ◽

Anna Rita Ciccaglione ◽

Giuseppina La Rosa ◽

Roberto Bruni ◽

...

Keyword(s):

Hepatitis E Virus ◽

Wastewater Treatment Plants ◽

National Level ◽

Hepatitis E ◽

Environmental Surveillance ◽

Information Campaigns ◽

Urban Sewage ◽

The One ◽

Autochthonous Transmission ◽

Undercooked Pork

Increasing numbers of hepatitis E cases are being reported in several European countries, including Italy, but the burden of hepatitis E virus (HEV) infection is largely unknown in the latter. To gain a better understanding of HEV epidemiology at national level in Italy, we piloted a strengthened and integrated human (epidemiological and virological) and environmental HEV surveillance system between 2012 and 2016. Over the 5-year period, 169 confirmed hepatitis E cases were identified, with a national annual incidence of 0.72 cases per 1,000,000. Of 65 HEV-RNA positive samples of sufficient quality for molecular analysis, 66% were genotype HEV3, 32% HEV1 and 1% HEV4. The most frequent risk factor reported by all HEV3 infected cases, was the consumption of undercooked pork and sausage. For the environmental surveillance, 679 urban sewage samples were collected from 53 wastewater treatment plants and HEV-RNA was detected in 38/679 of the samples. Among these, 25 (66%) were genotype HEV3 and the remaining were HEV1. We demonstrate that autochthonous transmission and environmental circulation of genotype HEV3 is adding to travel-related HEV transmission in Italy. We recommend the ‘One Health’ approach to integrated surveillance, and to include HEV-related messages within health information campaigns focussing on food security.

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Hepatitis E virus genotype 3 and sporadically also genotype 1 circulate in the population of Catalonia, Spain

Journal of Water and Health ◽

10.2166/wh.2009.120 ◽

2009 ◽

Vol 7 (4) ◽

pp. 664-673 ◽

Cited By ~ 30

Author(s):

Pilar Clemente-Casares ◽

Jesus Rodriguez-Manzano ◽

Rosina Girones

Keyword(s):

Hepatitis E Virus ◽

Western Europe ◽

Wastewater Treatment Plants ◽

Significant Risk ◽

Hepatitis E ◽

Human Populations ◽

Genotype 1 ◽

Genotype 3 ◽

Virus Genotype ◽

Urban Sewage

Autochthonous hepatitis E virus (HEV) strains have been described infecting populations of industrialized countries, previously considered as non-endemic areas. The HEV strains circulating in one of those areas in south-western Europe (Barcelona, Spain) have been studied by analysing amplicons obtained from HEV genomes identified in wastewater, biosolids and sludge. Six sewage and two biosolid HEV positive samples from urban wastewater treatment plants and two positive HEV sludge samples with animal contamination were analysed by cloning and sequencing of 10–12 clones per sample. The results proved the presence of HEV strains belonging to genotype 3 and also sporadically to genotype 1 in urban sewage and biosolids, showing the simultaneous circulation of diverse HEV strains in the human population of the studied area. Only HEV genotype 3 was identified in slaughterhouse sludge samples. The circulation of genotype 1 in industrialized areas may have further health implications since this genotype has been associated with important epidemics in developing areas. Contamination of food and water through their contact with sewage not properly treated and biosolids presenting HEV may represent a significant risk for human populations in relation to HEV even in industrialized areas.

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Prevalence of Hepatitis E Virus Infection among Laboratory Rabbits in China

Pathogens ◽

10.3390/pathogens10060780 ◽

2021 ◽

Vol 10 (6) ◽

pp. 780

Author(s):

Lin Wang ◽

Chunnan Liang ◽

Xiaobo Li ◽

Ji Wang ◽

Rui Fu ◽

...

Keyword(s):

Hepatitis E Virus ◽

Large Scale ◽

High Viral Load ◽

Hepatitis E ◽

Serum Samples ◽

Rna Detection ◽

Research Personnel ◽

Rna Quantification ◽

Beijing China ◽

Bile Samples

Hepatitis E virus (HEV) is zoonotic and the leading cause of acute viral hepatitis worldwide. Rabbit HEV can infect humans and is prevalent globally. It is reported that laboratory rabbits are also naturally infected with HEV. Therefore, it is important to investigate in a large scale the prevalence of HEV in laboratory rabbits. Serum samples were collected from 649 laboratory rabbits of 13 different commercial vendors in Beijing, China, from 2017 to 2019, and anti-HEV and HEV antigen (Ag) were tested. Fecal samples were collected from 50 laboratory rabbits from one of the vendors for HEV RNA detection. Six laboratory rabbits with natural HEV infection were euthanized and their liver, kidney, bile and urine samples were collected for HEV RNA quantification. Liver tissues were subjected to histopathology analysis. The overall positive rates of anti-HEV antibodies and HEV-Ag are 2.6% (15/588) and 7.9% (51/649), respectively. HEV RNA was detected in 12.0% (6/50) of the rabbits. High viral load of HEV RNA was detected in liver and bile samples. Liver inflammation was observed. HEV is circulating in laboratory rabbit population in China. Strict screening is crucial to ensure experimental accuracy and prevent zoonotic transmission to research personnel.

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High levels of Hepatitis E virus in wild boar hunted for domestic consumption in Central Italy

European Journal of Public Health ◽

10.1093/eurpub/cky214.003 ◽

2018 ◽

Vol 28 (suppl_4) ◽

Author(s):

P De Santis ◽

S Di Pasquale ◽

G La Rosa ◽

D De Medici ◽

G Micarelli ◽

...

Keyword(s):

Wild Boar ◽

Hepatitis E Virus ◽

Central Italy ◽

Hepatitis E ◽

Domestic Consumption

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Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz953 ◽

2019 ◽

Vol 71 (5) ◽

pp. 1204-1211 ◽

Cited By ~ 13

Author(s):

Nassim Kamar ◽

Florence Abravanel ◽

Patrick Behrendt ◽

Jörg Hofmann ◽

Georges Phillippe Pageaux ◽

...

Keyword(s):

Chronic Hepatitis ◽

Retrospective Study ◽

Multicenter Study ◽

Virological Response ◽

Hepatitis E Virus ◽

Large Scale ◽

Organ Transplant ◽

Hepatitis E ◽

Solid Organ Transplant ◽

Solid Organ

Abstract Background Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response. Methods Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months. Results After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event. Conclusions This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance. This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.

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First detection and molecular characterization of hepatitis E virus in water from wastewater treatment plants in Portugal

Annals of Agricultural and Environmental Medicine ◽

10.26444/aaem/90497 ◽

2018 ◽

Vol 25 (2) ◽

pp. 364-367 ◽

Cited By ~ 4

Author(s):

Ana Matos ◽

João Mesquita ◽

Daniel Gonçalves ◽

Joana Abreu-Silva ◽

Cristina Luxo ◽

...

Keyword(s):

Wastewater Treatment ◽

Molecular Characterization ◽

Hepatitis E Virus ◽

Wastewater Treatment Plants ◽

Hepatitis E

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Quantification and genetic diversity of Hepatitis E virus in wild boar (Sus scrofa) hunted for domestic consumption in Central Italy

Food Microbiology ◽

10.1016/j.fm.2019.02.005 ◽

2019 ◽

Vol 82 ◽

pp. 194-201 ◽

Cited By ~ 13

Author(s):

Simona Di Pasquale ◽

Paola De Santis ◽

Giuseppina La Rosa ◽

Kevin Di Domenico ◽

Marcello Iaconelli ◽

...

Keyword(s):

Genetic Diversity ◽

Wild Boar ◽

Sus Scrofa ◽

Hepatitis E Virus ◽

Central Italy ◽

Hepatitis E ◽

Domestic Consumption

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High prevalence of anti-hepatitis E virus antibodies among blood donors in central Italy, February to March 2014

Eurosurveillance ◽

10.2807/1560-7917.es.2016.21.30.30299 ◽

2016 ◽

Vol 21 (30) ◽

Cited By ~ 38

Author(s):

Claudia Lucarelli ◽

Enea Spada ◽

Gloria Taliani ◽

Paola Chionne ◽

Elisabetta Madonna ◽

...

Keyword(s):

Hepatitis E Virus ◽

Blood Donors ◽

Dietary Habits ◽

Central Italy ◽

Hepatitis E ◽

Developed Countries ◽

Genotype 3 ◽

Recent Infection ◽

Assay Sensitivity ◽

Prevalence Rate Ratio

Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in developed countries, which seems partly due to differences in assay sensitivity. Using validated sensitive assays, we tested 313 blood donors attending a hospital transfusion unit in central Italy in January and February 2014 for anti-HEV IgG and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was the only independent predictor of HEV infection (adjusted prevalence rate ratio = 2.14; 95% confidence interval: 1.23–3.74). Three donors were positive for either anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is therefore hyperendemic among blood donors (80% men 18–64 years-old) from central Italy and associated with local dietary habits. Nearly 1% of donors have acute or recent infection, implying potential transmission to blood recipients. Neither ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV infection.

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Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals

Euroasian Journal of Hepato-Gastroenterology ◽

10.5005/jp-journals-10018-1216 ◽

2017 ◽

Vol 7 (1) ◽

pp. 73-77 ◽

Cited By ~ 6

Author(s):

Birendra P Gupta ◽

Thupten K Lama

Keyword(s):

Chronic Hepatitis ◽

Virus Infection ◽

Acute Hepatitis ◽

Hepatitis E Virus ◽

Large Scale ◽

Hepatitis E ◽

Current Treatment ◽

Industrialized Nations ◽

Acute And Chronic Hepatitis

ABSTRACT Hepatitis E virus (HEV) infection results in nearly 20 million new infections, resulting in 70,000 deaths globally each year. Previously thought as a disease limited to developing nations with poor sanitation and hygiene, it is increasingly recognized that even the most developed nations are not spared. A clear dichotomy in epidemiology of HEV is noted between developing and industrialized nations. The HEV genotypes 1 and 2 are common in Asia and Africa and are transmitted mainly by contaminated drinking water. Sporadic as well as large-scale epidemics of acute hepatitis have been noted with HEV genotype 1 infection in developing countries of Asia and Africa. On the contrary, HEV genotypes 3 and 4 are common in industrialized nations and unlike genotypes 1 and 2, they are transmitted by consumption of raw meat products, fruits, and blood transfusion. Large epidemics have not been reported with HEV genotypes 3 and 4 and manifestation is usually indolent, though severe acute hepatitis has been reported. How to cite this article: Shrestha A, Gupta BP, Lama TK. Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals. Euroasian J Hepato-Gastroenterol 2017;7(1):73-77.

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