Systematic review and meta-analysis of hepatitis E seroprevalence in Southeast Asia: a comprehensive assessment of epidemiological patterns.

The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division.The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG-28.9%, IgM-4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV.A temporal analysis (1987-2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden.These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies.Key pointsResearch QuestionInvestigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts.FindingsSporadic Transmission of IgG and IgM Prevalence:• Pooled anti-HEV IgG prevalence: 21.03%• Pooled anti-HEV IgM prevalence: 3.49%Seroprevalence among specific groups:High-risk group (farm workers and chronic patients):• anti-HEV IgG: 28.9%• anti-HEV IgM: 4.42%Low-risk group (general population, blood donors, pregnant women, hospital patients):• anti-HEV IgG: 17.86%• anti-HEV IgM: 3.15%Temporal Seroprevalence of HEV:Anti-HEV IgG prevalence increased over decades (1987-1999; 2000-2010; 2011-2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27%ImportanceProvides a comprehensive overview of HEV seroprevalence in Southeast Asia.Highlights variation in seroprevalence among different population groups.Reveals increasing trend in HEV seroprevalence over the years.Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics.

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.

Incidence trends of acute viral hepatitis caused by four viral etiologies between 1990 and 2019 at the global, regional and national levels.

BACKGROUND: Hepatitis is a major public health challenge and a leading cause of death worldwide. We aimed to study the cause-specific incidence and temporal trends of acute viral hepatitis (AVH). METHODS: Data on AVH etiologies were available from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) was used to quantify temporal trend in AVH age-standardized incidence rates (ASIRs) by region, sex and aetiology. RESULTS: From 1990 to 2019, the global incidence of AVH increased by 8.02%, from 244 350 063 in 1990 to 263 951 645 in 2019, with an average decreasing ASIR of 0.52% (95% CI -0.58% to -0.45%) annually. The ASIR of AVH due to hepatitis B virus (HBV) decreased, while those of hepatitis A (HAV), hepatitis C (HCV) and hepatitis E (HEV) remained stable, with EAPCs (95% CI) of -1.47 (-1.58 to -1.36), 0 (-0.09 to 0.09), -0.35 (-0.83 to -0.13), and -0.16 (-0.41 to 0.09) respectively. Although the number of new AVH cases increased in the low sociodemographic index (SDI), low-middle SDI regions, the ASIRs decreased in all five SDI regions. Globally, HAV and HBV are the leading causes of acute hepatitis. The EAPC is significantly associated with a baseline ASIR of less than 5500 per 100 000 population (ρ = -0.44), and with the 2019 human development index (HDI) (ρ = 0.16) for AVH. CONCLUSIONS: Although the ASIR of AVH showed a generally decreasing trend, the burden of AVH remains a major public health challenge globally. The findings may be helpful for policymakers in establishing appropriate policies to reduce the viral hepatitis burden.

Assessment of hepatitis E seropositivity among HIV-infected patients in Bulgaria.

It is debatable whether HIV-infected patients are at greater risk for hepatitis E virus (HEV) infection compared with healthy subjects. The reported anti-HEV seroprevalence among different groups in Bulgaria varied from 9.04% to 25.9%, but the information regarding the HIV population is still missing. The aim of the present study was to evaluate hepatitis E seroprevalence among HIV-infected patients in Bulgaria and to analyze demographic and immunological factors associated with HEV infection. Serum samples of 312 HIV-infected patients were analyzed retrospectively. Age, sex, residence and laboratory markers for HEV, HBV, HCV and HIV infection, and lymphocytes subpopulations were collected for all patients. None of the tested samples were positive for HEV RNA. HEV seroprevalence among HIV-infected patients was 10.9%. Males were more affected with the highest prevalence of positivity in the age group > 30 to ≤ 40 years. The documented HIV transmission routes in HIV/HEV co-infected group were heterosexual, homosexual, intravenous drug use (IDU), and vertical with predominace of the heterosexual route (z = 0.2; p = 0.804). There was a statistically significant trend of HIV mixed infection with routes of HIV transmission other than homosexual - heterosexual in HIV/HEV group and injection drug use in HIV/HBV/HCV co-infected group. The route of HIV transmission, in contexts of patients' behavior, was associated with HEV prevalence among HIV-infected patients.

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.

Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation.

BACKGROUND: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.

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.

Controlling hepatitis E virus in the pig production sector: Assessment of the technical and behavioural feasibility of on-farm risk mitigation strategies.

Hepatitis E virus (HEV) is a zoonotic agent with pigs as the main reservoir in industrialised countries. Recent studies conducted on pig farms, in experimental conditions or through modelling approaches, have led to a better understanding of the spread of HEV on pig farms. The findings have also made it possible to define a set of measures to reduce HEV prevalence and the risk of marketing contaminated products. The objective of this study was to assess the feasibility of a set of HEV control strategies on pig farms. Individual semi-structured interviews were conducted with farmers, veterinarians and farming advisors to collect general data, their level of knowledge of HEV, their opinion on the technical feasibility of certain changes in practices, their perception of the respective responsibilities of the different stakeholders, and their feelings about the importance of the issue, following the framework of the Theory of Planned Behaviour. The interviews made it possible to highlight potential barriers and preferred motivators for the implementation of on-farm risk mitigation strategies. Barriers included lack of knowledge, scientific gaps, perceived inability to control HEV, and low perception of the importance of the issue. Motivators included professional satisfaction, family recognition, and the opportunity to achieve higher quality standards. Three clusters of stakeholders were also identified, with a group of leaders who could help unlock reluctance and disseminate innovations. This type of behavioural approach appeared useful to help risk managers facilitate zoonotic control on pig farms.

[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.

Targeted hepatitis E vaccination for women of childbearing age is cost-effective in China.

BACKGROUND: Hepatitis E virus (HEV) infection is hyper-endemic in China, it is characterized with a high morbidity of fulminant hepatitis and mortality in pregnant women. The first hepatitis E vaccine, HEV 239, was licensed in China in 2011 which provides an effective preventive measure. OBJECTIVE: To evaluate the cost-effectiveness of vaccination with HEV 239 in women of childbearing age in China and whether HEV antibody screening should be considered before vaccination. METHODS: A decision tree-Markov model was constructed to simulate HEV infection in a closed female cohort with an average first-marriage age of 25 years and evaluate health and economic outcomes of two potential vaccination strategies, direct vaccination and combined screening and vaccination, from a societal perspective. An incremental cost-effectiveness ratio (ICER, additional costs per disability-adjusted life-year (DALY) averted) was calculated for each vaccination strategy versus no vaccination and between two vaccination strategies. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of the model findings. RESULTS: ICERs of direct vaccination and combined screening and vaccination versus no vaccination were $4040 and $3114 per DALY averted, respectively, much lower than 1-time Chinese per-capita GDP ($8127). Direct vaccination would need additional $45,455 for each DALY averted compared with combined screening and vaccination, far more than the 3-time per-capita GDP. Probabilistic sensitivity analyses confirmed our findings that two vaccination strategies would be cost-effective if the willingness-to-pay reached the 1-time per-capita GDP, and that combined screening and vaccination would be more cost-effective than direct vaccination strategy. CONCLUSION: Vaccinating women of childbearing age with HEV 239 would cost less than the 1-time per-capita GDP for each DALY averted in China, and the vaccination with a prior screening would be the optimal option.