Global burden of acute hepatitis E between 1990 and 2019 and projections until 2030.

BACKGROUND AND AIMS: Acute hepatitis E (AHE) is still a public health issue worldwide. Here, we report the global burden of AHE in 204 countries and territories from 1990 to 2019 by age, sex and socio-demographic index (SDI), and predict the future trends to 2030. METHODS: Data on AHE were collected from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. The average annual percentage change (AAPC) and joinpoint analysis were used to determine the burden trend. RESULTS: In 2019, there were 19.47 million (95% UI, 16.04 to 23.37 million) incident cases of AHE globally, with a 19% increase since 1990. Age-standardized rate (ASR) of disability-adjusted life years (DALYs), prevalent and incident cases declined from 1990 to 2019. In 2019, the ASR of incidence, prevalence and DALYs due to HEV infection were highest in the same regions of South Asia for both sexes. Southern Sub-Saharan Africa presented the highest increases in the ASR for incidence of HEV infection in both males (AAPC = .25) and females (AAPC = .24) from 1990 to 2019. Incident cases are higher in males than females before 55-59 years old. The SDI values were negatively correlated with the age-standardized DALYs. Between 2019 and 2030, the ASR for incidence and prevalence of HEV for both sexes showed an increasing trend. CONCLUSIONS: Although the overall ASR of AHE decreased, the burden of AHE remains an underappreciated problem for society. The findings may provide useful information for policymakers to develop appropriate strategies aimed at reducing the burden of AHE.

Hepatitis E virus in pork meat products and exposure assessment in Belgium.

Zoonotic hepatitis E virus (HEV) genotype 3 infections are the predominant cause of acute viral hepatitis in Europe, mostly associated with the consumption of HEV contaminated pork meat. In this study we looked at the HEV RNA positivity rate of pork meat products readily available from Belgian supermarkets and evaluated the overall HEV consumer exposure in a Belgian context. Two basic assessments were performed in a 'worst-case' scenario setting: one solely focusing on the contamination level of the product itself (ingredients and processing parameters) and another estimating the overall consumer exposure, taking into account consumption habits in Belgium. Non-thermal-processed ready-to-eat (i.e. ready for consumption without additional cooking step by consumer) pork meat products (e.g. raw dried sausages), had a high estimated HEV contamination level, while thermal-processed ready-to-eat pork meat products (e.g. pork liver pâté) had the highest overall consumer exposure estimates. Following these assessments, pork liver pâtés, raw dried hams and raw dried sausages (n = 54) were purchased from Belgian supermarkets (n = 3) and analyzed for HEV RNA by RT-PCR. In total, 31 % (n = 17) products tested positive. HEV RNA was found in 65 % of the pork liver pâtés, 15 % of raw dried hams and 0 % of raw dried sausages. Phylogenetic analysis of four isolates (all gt3c) from pork liver pâté samples showed similarities with human clinical cases from Germany and Belgium.

Assessment of Knowledge, Attitude, and Practice among Saudi Residents Regarding Hepatitis E Virus.

Global data, including those from Saudi Arabia, that examined public knowledge, attitudes, and practices (KAP) toward hepatitis E virus (HEV) are limited. This study examined KAP levels of the general population in Saudi Arabia toward HEV. A cross-sectional study was conducted among 768 participants. An Arabic electronic questionnaire that contained demographic data and had 35 questions was used to measure KAP of the participants concerning HEV. Collected data were analyzed at a significance level of 0.05. A total of 768 individuals participated in the study, of whom 16.3% (N = 125) were males and 83.7% (N = 643) were females. Study subjects were 18 years and above. Most of the participants were Saudi citizens (95.6%; N = 734), and from Western Saudi Arabia (76.4%; N = 587). Thirty-four percent (N = 261) of the participants had not heard of HEV, and 48% were aware that yellowish skin or eyes are the most important sign of hepatitis. The level of participants' knowledge about HEV was low (39.5%). However, positive attitudes and practices were apparent and tended to aim at how to avoid becoming infected with HEV. In conclusion, the level of HEV-related knowledge among the participants was low, and their practices and attitudes were aimed at avoiding HEV infection. Awareness campaigns are required to increase the public's HEV-related knowledge.

Assessment of subclinical effects of Hepatitis E virus infection in the United States.

Some studies have exposed an increase in liver cirrhosis in hepatitis E seropositive individuals living with human immunodeficiency virus. The interrelation between HEV seroprevalence and risk of liver disease in immune-competent individuals remains under- investigated. Using the National Health and Nutrition Examination Survey (NHANES) data containing >30,000 subjects, we addressed if HEV exposure leads to subclinical effects that can influence liver health. We determined the association between HEV IgM and ALT and that of HEV IgG and Fib-4-a composite score reflecting potential liver fibrosis. These analyses were repeated in populations at risk for liver disease as well as among different races and ethnicities. The prevalence of HEV IgG was significantly associated with age as IgG positive individuals were, on average, 20 years older than IgG negative patients. We found a statistically significant increase in the likelihood of having a Fib-4 score >1.45 (significant fibrosis) in those positive for HEV IgG (RR: 1.03; 95% CI: 1.01-1.05). However, due to the small effect, it is unlikely that this association has clinical significance. Moreover, the effect was not present in those with pre-existing liver disease. We found no association between ALT levels and the presence of HEV IgM or IgG. This is the first study examining subclinical effects of HEV infection in the United States. Our study found that in the general US population, predominantly asymptomatic HEV infections do not contribute to the overall burden of liver disease.

Hepatitis E-Associated Hospitalizations in the United States: 2010-2015 and 2015-2017.

Hepatitis E is considered rare in the United States (US) despite its widespread occurrence in Asian and African countries. The objective of this study was to describe the characteristics of hepatitis E-related pregnancies and acute-on-chronic liver failure and analyse trends for hepatitis E diagnosis among hospitalized patients in the US. We examined data from the 2010-2017 National Inpatient Sample from Healthcare Cost and Utilization Project to determine mortality, morbidity, pregnancy diagnoses, chronic liver disease diagnoses, and other conditions during hospitalization. Data were extracted for hospitalizations with hepatitis E as defined by ICD-9 codes 070.43 and 070.53 and ICD-10 code B17.2. Of 208,462,242 hospitalizations from 2010-2015, we identified 960 hepatitis E hospitalizations. The hospitalization rate of hepatitis E was 3.7 per 10 million in 2010 and 6.4 per 10 million in 2015 (ß = 0.60, p = 0.011). From 2015 to 2017, the hospitalization appeared to increase with slope (ß) of 0.50. Among those hospitalizations, 34 (4%) died and 85 (9%) had acute-on-chronic liver failure. Ninety-five (10%) had a diagnosis of pregnancy, there were no reports of maternal or foetus/neonate deaths, but there was a high proportion of adverse events for both during hospitalization. Having a chronic liver disease was associated with hepatic coma diagnosis (OR = 10.94, p = 0.002). Although the hospitalization rate of hepatitis E in the US is low, it appears to be increasing over time. Further studies are necessary in order to conclude a causal association of hepatitis E with adverse events and mortalities in pregnancy and chronic liver disease in the US.

Assessment of hepatitis E virus (HEV) in the edible goat products pointed out a risk for human infection in Upper Egypt.

Hepatitis E virus (HEV) infection is endemic in developed and developing countries. Although the seroprevalence of HEV among the Egyptians is high, the sources of HEV infection in Egypt are not completely identified. Zoonotic HEV transmission among Egyptians is underestimated. Recently, we detected HEV in the milk of cows, this suggests the possibility of HEV transmission through the ingestion of contaminated milk. However, the role of small ruminants especially the goats in HEV epidemiology in Egypt remains unclear. Herein, we screened HEV markers in the edible goat products, mainly the milk and liver and we assessed the risk factor for HEV infection to the goat owners. A total of 280 goat milk samples were collected from 15 villages in the Assiut governorate. Anti-HEV IgG and HEV Ag were detected in 7.14% and 1.8% of the samples, respectively. HEV RNA was detected in 2 milk samples, cladogram analysis revealed that the isolated viruses belonged to HEV-3 subtype 3a. One viral isolate showed high homology to HEV recently isolated from the cow milk in the same geographic area. The level of anti-HEV IgG and HEV Ag were comparable in the milk and matched blood samples. While the urine and stool of HEV seropositive goats tested negative for HEV markers. HEV RNA was also detectable in the fresh goat liver samples (n = 2) derived from HEV seropositive goats. Finally, we analyzed HEV seroprevalence in households (n = 5) that owned the seropositive goats and households (n = 5) that owned the seronegative goats. Interestingly, anti-HEV IgG was recorded in 80% of households owned and frequently consumed the products of HEV seropositive goats, while HEV markers were not detectable in the owners of the seronegative goats. In conclusion: Here, we report HEV in the milk and liver of goats distributed in the villages of Assiut governorate. Higher HEV seroprevalence was recorded in the households that owned the seropositive goats. Investigation of the goat products is pivotal to assess the risk factor of HEV transmission to villagers in the Assiut governorate.

Disease burden concerning hepatitis E-infected inpatients in Jiangsu province, China.

OBJECTIVE: This study aimed to determine the disease burden of hepatitis E virus (HEV)-infected inpatients in Jiangsu province, China. METHODS: Between July 1, 2016 and October 31, 2018, 1152 HEV-infected inpatients were identified from four cities in Jiangsu province, namely, Nanjing, Suzhou, Yancheng, and Zhenjiang. The disease burden comprised the economic burden and loss of health due to HEV infection. Factors influencing the disease burden were analyzed using univariate and multivariate analyses. RESULTS: The average direct, indirect, and total economic burden for 1152 HEV-infected inpatients was US$ 4,986.40, US$ 1,507.28, and US$ 6,493.68, respectively, accounting for 46.66%, 14.11%, and 60.77% of per capita disposable income (PCDI) in Jiangsu province, respectively. The disease burden for HEV-infected inpatients with hepatitis B was significantly higher than that for other inpatients. The average EQ-5D utility value of 1152 HEV-infected inpatients was 0.72 ±â€¯0.18 quality-adjusted life years (QALYs) and the average EQ-visual analogue score (EQ-VAS) was 0.66 ±â€¯0.17 points. Multivariate analysis showed that the direct economic burden and the total economic burden were influenced by variables such as hospitalization days, outcomes, past history of other diseases, and regions (P < 0.05). It was estimated the direct economic burden, the indirect economic burden, and the total economic burden for all HEV-infected inpatients in Jiangsu province in 2018 was approximately US$ 9.2 million, US$ 2.8 million and US$ 12.0 million, respectively. CONCLUSION: The disease burden of HEV infection in Jiangsu province is severe, and more attention should be paid to the prevention of hepatitis E and the treatment of comorbidities.

[Hepatitis E Virus: Epidemiology, Diagnosis, and Management].

The HEV is a known cause of water-borne outbreaks of acute non-A non-B hepatitis in developing countries, which affects young people and may result in high mortality in pregnant women. In recent decades, however, HEV genotypes 3 and 4 have been known as a cause of sporadic zoonotic infections in older males from swine HEV worldwide. Most acute HEV infections are self-limited. On the other hand, in immunosuppressed patients, including solid organ transplant recipients, chronic HEV infections may exist and progress to liver cirrhosis or decompensation. Therefore, physicians need to recognize HEV as a major pathogen for acute and chronic hepatitis of unknown causes and investigate this disease.

Hepatitis E Virus Infection in Blood Donors and Risk to Patients in the United States and Canada.

Hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide including large water-borne outbreaks, zoonotic infections and transfusion transmissions. Several countries have initiated or are considering blood donor screening in response to high HEV-RNA donation prevalence leading to transfusion-transmission risk. Because HEV transmission is more common through food sources, the efficacy of blood donor screening alone may be limited. HEV-nucleic acids in 101 489 blood donations in the United States and Canada were studied. A risk-based decision-making framework was used to evaluate the quantitative risks and cost-benefit of HEV-blood donation screening in Canada comparing three scenarios: no screening, screening blood for all transfused patients or screening blood for only those at greatest risk. HEV-RNA prevalence in the United States was one per 16 908 (95% confidence interval [CI], 1:5786-1:81987), whereas Canadian HEV-RNA prevalence was one per 4615 (95% CI, 1:2579-1:9244). Although 4-fold greater, Canadian HEV-RNA prevalence was not significantly higher than in the United States. Viral loads ranged from 20 to 3080 international units per mL; all successfully typed infections were genotype 3. No HEV-RNA false-positive donations were identified for 100 percent specificity. Without donation screening, heart and lung transplant recipients had the greatest HEV-infection risk (1:366962) versus kidney transplant recipients with the lowest (1:2.8 million) at costs of $225 546 to $561 810 per quality-adjusted life-year (QALY) gained for partial or universal screening, respectively. Higher cost per QALY would be expected in the United States. Thus, HEV prevalence in North America is lower than in countries performing blood donation screening, and if implemented, is projected to be costly under any scenario.

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver.

Seroprevalence and risk assessment of viral hepatitis E infection in a group of exposed persons from Republic of Moldova.

INTRODUCTION: Viral hepatitis E is considered to be an important issue for public health in developing countries. The aim of the present study is to evaluate morbidity and risk factors in occupationally exposed groups such as people working on sausage production. METHODOLOGY: Seroprevalence of HEV (hepatitis E virus) and risk factors to infection were determined in a cross-sectional study of two groups of populations: people working on sausage production (n = 70) and persons without occupational exposure (people working in the textile industry n = 70) in Moldova, a country without reported cases of hepatitis E. RESULTS: The seroprevalence of HEV was 14.3% (CI 95%, 13.1-15.5%) in the group of exposed, compared with no cases in the non-exposed group that indicates on no previous infectious contact with hepatitis E virus. CONCLUSIONS: The increased seroprevalence of HEV among persons with occupational exposure to swine meat suggest animal-to-human transmission of this infection.

Toward Systematic Screening for Persistent Hepatitis E Virus Infections in Transplant Patients.

BACKGROUND: Persistent hepatitis E virus genotype 3 (HEV G3) infections affect solid organ transplant (SOT) recipients and hematopoietic stem cell transplant (HSCT) recipients, but the burden in these cohorts in the United Kingdom is unknown. We established an audit to determine the point prevalence of HEV viremia in SOT and HSCT patients in the United Kingdom and compare different testing approaches to inform screening strategies. METHODS: Between January 5, 2016, and September 21, 2016, 3044 patients undergoing therapeutic drug monitoring at a single transplant center were screened for HEV ribonucleic acid (RNA) in minipools. A total of 2822 patients who could be characterized included 2419 SOT patients, 144 HSCT patients and 259 patients with no available transplant history. HEV RNA-positive samples were characterized by serology and genomic phylogeny. HEV antigen (HEV-Ag) testing was performed on RNA-positive samples, 420 RNA-negative samples and 176 RNA-negative blood donor samples. RESULTS: Nineteen of 2822 patients were viremic with G3 HEV giving a prevalence of 0.67%. The median alanine aminotransferase was significantly higher in the HEV viremic patients (P < 0.0001); however, 2 viremic patients had an alanine aminotransferase value within the normal range at the time of screening. The HEV-Ag assay identified 18/19 viremic patients and all those patients with proven viremia longer than 4 weeks. CONCLUSIONS: Transplant recipients in the United Kingdom are at a low but significant risk of HEV infection. HEV-Ag detection could be an alternative to RNA detection where the goal is to identify established persistent HEV infection, particularly where expertise, facilities, or cost prohibit RNA testing.

Hepatitis E virus RNA in Australian blood donors: prevalence and risk assessment.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS: Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS: One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION: Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.

Health economic evaluation of immunization strategies of hepatitis E vaccine for elderly population.

Objective This study was conducted to assess the cost-effectiveness of hepatitis E vaccination of elderly population in the sporadic regions in China. Methods We used a decision tree-Markov model to evaluate the cost-effectiveness of 3 kinds of hepatitis E virus vaccination strategies from societal perspectives. Parameter estimates were obtained from published researches and experts' opinion. The time horizon was 16 years, and the discounted rate was 3% annually. Costs are expressed in 2016 US dollars. Results The universal vaccination strategy had an incremental cost-effectiveness ratio (ICER) of US$ 8475.90 per QALY gained versus no vaccination. The implementation of screening and vaccination strategy would have an ICER of US$ 4044.28, compared with no vaccination. The vaccination was cost-effective (ICER< 3 times China's per capital gross domestic product/quality-adjusted life years). The QALY of asymptomatic infection, vaccine coverage and vaccine protection are the important parameters impacting the ICER in one-way sensitivity analysis and screening and vaccination being the dominant strategy in probabilistic sensitivity analysis. Conclusion This analysis indicates that screening and vaccination is the most cost-effective hepatitis E intervention strategy of elderly population in sporadic region in China.

Prevalence and Molecular Characterization of the Hepatitis E Virus in Retail Pork Products Marketed in Canada.

Infection with the hepatitis E virus (HEV) is very common worldwide. HEV causes acute viral hepatitis with approximately 20 million cases per year. While HEV genotypes 1 and 2 cause large waterborne and foodborne outbreaks with a significant mortality in developing countries, genotypes 3 and 4 are more prevalent in developed countries with transmission being mostly zoonotic. In North America and Europe, HEV has been increasingly detected in swine, and exposure to pigs and pork products is considered to be the primary source of infection. Therefore we set out to investigate the prevalence of HEV in retail pork products available in Canada, by screening meal-size portions of pork pâtés, raw pork sausages, and raw pork livers. The presence of the HEV genomes was determined by RT-PCR and viral RNA was quantified by digital droplet PCR. Overall, HEV was detected in 47% of the sampled pork pâtés and 10.5% of the sampled raw pork livers, but not in the sampled pork sausages, and sequencing confirmed that all HEV strains belonged to genotype 3. Further phylogenetic analysis revealed that except for one isolate that clusters with subtype 3d, all isolates belong to subtype 3a. Amino acid variations between the isolates were also observed in the sequenced capsid region. In conclusion, the prevalence of HEV in pâtés and raw pork livers observed in this study is in agreement with the current HEV distribution in pork products reported in other developed countries.

[Use the Markov-decision tree model to optimize vaccination strategies of hepatitis E among women aged 15 to 49].

Objective: To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49. Methods: The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies. Parameters of the models were estimated on the basis of published studies and experience of experts. Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model. Results: Compared with non-vaccination group, strategy on post-screening vaccination with rate as 100%, could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives. After implementation of screening program and with the vaccination rate reaching 100%, the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 Yuan/QALY, respectively. Vaccination post to the implementation of a screening program, the result showed better benefit than the vaccination rate of 100%. Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects. If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23, the vaccination rate of 100% strategy was better than the post-screening vaccination strategy, otherwise the post-screening vaccination strategy appeared the optimal strategy. Conclusion: Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.

Disease burden of hepatitis E in a rural population in China: a community-based survey.

This study aimed to estimate the disease burden of hepatitis E in a rural region in China. A total of 489 hepatitis E cases were reported according to a community-based survey in an active hepatitis surveillance system between 2008 and 2015, the questionnaire and record-review methods were constructed to evaluate the economic and health burden of hepatitis E virus infections from societal perspectives. All costs were converted to US$ in 2015. The age-standardized cumulative incidence rate was 107·9/100 000, and the median age-standardized annual incidence rate was 16·5/100 000. The median direct, indirect, and intangible cost were $1046·0, $49·1, and $77·3/patient, respectively, and the median economic burden per patient was $1836·5, which accounted for 51·2% of per capita disposable income. Moreover, the median quality-adjusted life year and visual analogue scale score were 0·7 and 70·0/case, respectively. Both economic burden and health burden of inpatients was more serious than that of outpatients (P < 0·001). Disease burden of hepatitis E is heavy on patients, their families, and society. More studies on the disease burden of hepatitis E are necessary to increase social awareness of the disease and confirm reasonable disease-control measures.

Assessment of the risk of foodborne transmission and burden of hepatitis E in Switzerland.

The objective of this study was i) to quantify the risk of hepatitis E for Swiss consumers by specified pork products and ii) to estimate the total burden of human food-borne hepatitis E in Switzerland. A quantitative risk assessment from slaughter to consumption was carried out according to the Codex Alimentarius framework. In the hazard characterization, assumptions were made due to the lack of a dose-response relationship for oral exposure to hepatitis E virus (HEV). The prevalence of HEV in 160 pig livers of 40 different Swiss fattening farms was examined and determined to be 1.3% (CI 0.3%; 4.4%). This result was used as input in the risk assessment model, together with data from other published studies. The annual burden of hepatitis E was estimated in terms of Disability Adjusted Life Years (DALY), using data about hepatitis E cases diagnosed between 2010 and 2015 at two major hospitals located in the canton Ticino. Only the risk of foodborne hepatitis E from products containing pork liver was evaluated, as those containing only pork meat could not be evaluated because of lack of data on HEV load in pork. Assuming that successful oral infection occurs in 1% of servings contaminated with high HEV loads (>105 genome copies), and that acute illness develops in 5% of susceptible consumers, the most likely annual number of foodborne hepatitis E cases in Switzerland was estimated to be 1481 (95% CI 552; 4488) if all products containing pork liver were considered. If only high-risk products, such as plain pork liver and liver sausages (e.g. Saucisse au Foie), were considered, the annual number of cases was estimated to be 176 (95% CI 64; 498). We were unable to calculate the total burden of hepatitis E in Switzerland due to lack of data. Yet, for the canton Ticino, it was shown that a significant increase had occurred from <5 DALY per 100,000 inhabitants before 2012 to >50 DALY per 100,000 inhabitants in 2015. This change could partly be due to an increased reporting and higher awareness among medical practitioners. Extrapolation to other regions could be accomplished if detailed information on food consumption patterns were available. Notification of HEV cases and attempts of cases source attribution would improve the basis for risk assessments.

The global burden of hepatitis E outbreaks: a systematic review.

Hepatitis E virus (HEV) is responsible for repeated water-borne outbreaks since the past century, representing an emerging issue in public health. However, the global burden of HEV outbreak has not been comprehensively described. We performed a systematic review of confirmed HEV outbreaks based on published literatures. HEV outbreaks have mainly been reported from Asian and African countries, and only a few from European and American countries. India represents a country with the highest number of reported HEV outbreaks. HEV genotypes 1 and 2 were responsible for most of the large outbreaks in developing countries. During the outbreaks in developing countries, a significantly higher case fatality rate was observed in pregnant women. In fact, outbreaks have occurred both in open and closed populations. The control measures mainly depend upon improvement of sanitation and hygiene. This study highlights that HEV outbreak is not new, yet it is a continuous global health problem.

Seroepidemiology of HEV and HAV in two populations with different socio-economic levels and hygienic/sanitary conditions.

The epidemiological scenarios of hepatitis E virus (HEV) and hepatitis A virus (HAV) infections have changed in the last few decades, but precise epidemiological data on the prevalence of anti-HEV and anti-HAV, alone or in combination, in the general population are scanty. We investigated HEV and HAV seroprevalence comparing two population samples living in Northern (Abbiategrasso, Milan) and Southern Italy (Cittanova, Reggio Calabria), the latter being characterized by a poorer socio-economic level and hygienic/sanitary conditions. Based on census records, we randomly enrolled and tested 3,365 subjects (Abbiategrasso, n = 2,489; Cittanova, n = 876) aged 18-75 years for anti-HAV and anti-HEV. Anti-HAV (71.3 % vs 52.5 %) and anti-HEV (17.8 % vs 9.0 %) prevalence rates were higher in Southern Italy (both p < 0.001). Most anti-HEV-positive subjects also had anti-HAV. Subjects testing positive for anti-HAV, alone or with anti-HEV, were older (p < 0.001 in both populations) and showed a trend toward declining prevalence in the youngest birth cohorts. The prevalence of subjects with a positive result for anti-HEV alone did not change in birth cohorts in the two towns. Detection of anti-HEV was independently associated with anti-HAV, town, birth cohort, and education level in multivariate analysis. Low socio-economic level and hygienic/sanitary conditions are associated with high HAV and HEV seroprevalence rates in Italy. Recent improvements, especially in the South, have led to a declining prevalence of anti-HAV, alone or with anti-HEV. Seroprevalence of HEV alone is uniformly low and does not change in birth cohorts born between 1938 and 1993.