Seroepidemiology of Hepatitis A and Hepatitis E Infections in Ardabil, Northwest of Iran: A Cross-sectional Population Based Study

We read the articles by Kamar et al.1 and Haagsma et al.2 with interest. The authors reported for the first time a few cases of chronic hepatitis related to hepatitis E virus (HEV) infection in organ transplant recipients with progression to cirrhosis, and they suggested that these subjects could be long-term carriers of the infection. Hepatitis E infection typically causes acute hepatitis with spontaneous recovery in almost all cases. Very few cases have been associated with fulminant hepatitis. The disease predominates in developing countries with tropical or subtropical climates because HEV is mainly transmitted enterically through contaminated water. In industrialized countries, hepatitis E is considered an emerging disease formerly associated with travel to highly endemic regions. However, in the last few years, sporadic cases of HEV infection related to the spread of autochthonous viral strains have been detected, and this suggests a zoonotic transition from pigs.3, 4 The potential risk of persistent HEV infection with chronic liver disease has been described in select clinical situations characterized by reduced immunocompetence, such as those induced by chemotherapy5 or immunosuppression.6 This possibility has not been widely analyzed because of the difficulties in establishing the diagnosis of HEV infection. Its diagnosis is limited by the lack of commercial assays for detecting HEV RNA and the lack of assays that are able to determine anti-HEV immunoglobulin M (IgM) antibodies. We recently reported a prevalence of anti-HEV immunoglobulin G (IgG) of 7.33% in healthy adults in Spain.7, 8 There are no data regarding the frequency of anti-HEV antibodies in solid organ recipients in our area. Therefore, we tested for anti-HEV immunoglobulin antibodies in 108 serum samples from consecutive liver and kidney recipients who were controlled in our center between July and August 2008 and who had elevated alanine aminotransferase (ALT) levels greater than 1.5 times the upper normal limit. Among them, 71 (65.7%) were males with a mean age of 54.9 years (range: 19–75). Eighty-two were liver recipients, 21 were renal transplant recipients, and 5 were dual-organ recipients. Serum samples positive for anti-HEV IgG were also tested for serum anti-HEV IgM and HEV RNA. Anti-HEV IgG and IgM were determined with immunoenzymatic assays (Bioelisa HEV IgG and Bioelisa HEV IgM, Biokit, Barcelona, Spain), and HEV RNA was determined by real-time polymerase chain reaction. Anti-HEV IgG antibodies were detected in only 3 solid organ recipients (2.7%). All 3 patients were liver recipients diagnosed with chronic hepatitis C, and they were negative for anti-HEV IgM and serum HEV RNA. Two were males (mean age: 65.9 years; range: 65–73), with a mean time after transplantation of 60.73 months (range: 19–94 months), and they had median ALT levels 1.9 times the normal values. Among patients without anti-HEV IgG antibodies, 69 (65.7%) were males, with a mean age of 54.5 years (range: 19–75), a mean time after transplantation of 47.49 months, and mean ALT levels 2.7 times the normal values. There were no statistically significant differences between the groups. Second serum samples from those 3 patients with anti-HEV IgG antibodies, obtained 6 months later, showed the persistence of these antibodies; the samples were negative for anti-HEV IgM and HEV-RNA, and an active HEV infection was ruled out. Our results showed similar frequencies of detection of anti-HEV IgG antibodies in the general population and in solid organ transplant recipients; the frequency was even lower in comparison with the anti-HEV IgG detection rate of 12% in the same age group in the general population. These results contradict previous reports from areas with a low rate of HEV prevalence suggesting that solid organ transplant recipients and even selected patients with abnormal ALT levels could be a risk population for HEV infection. A previous report from Spain found a higher prevalence of HEV antibodies neither in patients with hemophilia nor in patients on hemodialysis.8 Further studies are needed to determine the real prevalence of hepatitis E in transplant recipients and the possible causes of the epidemiological differences between regions in Europe. Maria Buti* , Cecilia Cabrera* , Rosendo Jardi* , Luis Castells* , Rafael Esteban* , * Liver Unit, Vall d'Hebron General University Hospital, Barcelona, Spain, Network Center for Biomedical Research in Hepatic and Digestive Diseases, Carlos III Health Institute, Barcelona, Spain.

Background:Enterically-transmitted acute viral hepatitis is caused predominantly by hepatitis A virus (HAV) and hepatitis E virus (HEV). The prevalence of HEV and HAV infections varies in different geographical regions.Objectives:This study was conducted to determine the prevalence of HEV and HAV infections among Iranian healthy individuals in southern Iran.Patients and Methods:Totally, 1030 samples were collected from healthy subjects in schools, those referred to tertiary outpatient clinics and health centers in Shiraz between November 2011 and May 2012. Their ages ranged between six months and 95 years. The presence of total anti-HAV and anti-HEV immunoglobulin M (IgM) in plasma was assessed by ELISA.Results:The results showed that 66.2% and 0.6% of the general population in this area were positive for total anti-HAV and IgM antibodies by ELISA, respectively. As seen, 13.4% and 0.9% were positive for total anti-HEV and IgM antibodies, respectively. The difference in total anti-HAV and anti-HEV antibodies was significant among the age groups (P < 0.001).Conclusions:This study showed that the prevalence rates of HAV and HEV antibodies were positively correlated with age. The results demonstrated that the infection with these two viruses in the region was high and some high-risk individuals including females at child-bearing age were more susceptible. HAV vaccination could be recommended for antibody-negative adults.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) continue to represent a significant global public health challenge. This study aims to assess the seroprevalence of anti-HAV immunoglobulin G (IgG) and anti-HEV IgG antibodies among blood donors in Paraguay, a region where epidemiological data on these infections are scarce. Serum samples were collected from 452 blood donors in five regions of Paraguay and the presence of anti-HAV IgG and anti-HEV IgG antibodies was assessed. Overall, 68.1% of donors tested positive for anti-HAV IgG, with a higher prevalence in older age groups (p<0.001) and significant regional differences (p<0.001). Notably, a low seroprevalence was found in the 18- to 25-y age group (36.4%), highlighting a potential gap in immunity. In contrast, anti-HEV IgG was detected in 6.0% of samples, with no significant differences observed across age groups or regions. Men exhibited a non-significant trend toward higher anti-HEV IgG seroprevalence compared with women (p=0.082). The high seroprevalence of anti-HAV IgG among older blood donors contrasts sharply with low coverage in younger adults, underscoring the critical need to prioritize and expand HAV vaccination efforts in younger adults. Furthermore, the low HEV seroprevalence suggests an opportunity for proactive surveillance and prevention, potentially addressing recent introduction or limited transmission. These results offer a valuable epidemiological foundation to guide effective disease control strategies and public health programs in Paraguay.

Background:Hepatitis A virus (HAV) and hepatitis E virus (HEV) are transmitted by the fecal-oral route and are responsible for epidemic and sporadic outbreaks of acute hepatitis in low-income countries like Bangladesh.Objective:The purpose of this study was to describe the seroprevalence of acute hepatitis due to HAV and HEV infection in Bangladesh.Methods:The nationwide food-borne illness surveillance started in 2014 at 10 different hospitals which covered seven divisions of Bangladesh. Blood samples were collected from suspected acute hepatitis cases and screened for the anti-HAV IgM and anti-HEV IgM using enzyme-linked immunosorbent assay (ELISA). Participants’ socioeconomic status, clinical, sanitation and food history were recorded. Multivariate logistic regression was performed to determine the risk factors associated with HAV and HEV infection.Findings:A total of 998 patients were enrolled and tested for both HAV and HEV. Among these, 19% (191/998) were identified as HAV positive and 10% (103/998) were HEV positive. The median age was 12 years and 25 years for HAV and HEV positive patients, respectively. The prevalence of HAV was higher among the females (24.9%), whereas HEV was higher among males (11.2%). The highest occurrence of HAV was observed among children while HEV was most prevalent in the 15–60 years age group (12.4%).Conclusion:Through our nationwide surveillance, it is evident that hepatitis A and hepatitis E infection is common in Bangladesh. These data will be useful towards planning preventive and control measures by strengthening the sanitation programs and vaccination strategies in Bangladesh.

Throughout the world, there has been growing concern over the risk of hepatitis E virus (HEV) transmission via blood transfusion. The present study screened blood donor samples for anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG). The prevalence of HEV infection was assessed on a total of 1,003 archived serum samples obtained from the National Blood Centre, Malaysia. The samples were collected from healthy blood donor from Klang Valley between 2017 and 2018. All samples were tested for IgM and IgG antibodies to HEV using enzyme-linked immunosorbent assays (ELISA). HEV-specific IgG antibodies were detected in 31/1003 (3.1%; 95% confidence interval [CI] 2.1%–4.4%) and IgM in 9/1003 (0.9%; 95% CI 0.4%–1.7%) samples. In bivariate analysis, there was no significant difference in the prevalence of anti-HEV IgG with respect to gender and district of origin. Although not statistically significant, males had higher odds of having anti-HEV IgG than females (odds ratio [OR] = 2.86; 95% CI 0.95–8.64). All anti-HEV IgG positive individuals were people of Chinese descent. Anti-HEV IgG increased significantly with age, from 0.6% (95% CI 0.1%–2.6%) of 18–30-year-old donors to 7.4% (95% CI 2.7%–17.0%) of donors older than 50 years and was highest among non-professional workers (5.3%; 95% CI 2.5%–10.5%). Increasing age and a non-professional occupation remained significant predictors for anti-HEV IgG in the multivariable analysis. Screening of blood donations for HEV in Malaysia is important to safeguard the health of transfusion recipients. The higher rates of HEV infection in blood from older donors and donors who are non-professional workers may provide insights into targeted groups for blood screening.

The World Health Organization (WHO) estimates that every year hepa -titis A virus (HAV) infection causes nearly 1.4 million new cases worldwide and the hepatitis E virus (HEV) is re-sponsible for 20 million new infections and over 3 million acute cases. Although in most cases HAV and HEV infections are self-limiting, HAV is estimated to kill 100 000 people each year [1] and HEV nearly 60000 people annually [2]. Pregnant women are at risk of more severe disease, obstetric complications and increased mortality if infected in the third trimester of pregnancy. The faecal–oral route is a well-established mode of transmission for both HAV and HEV and in the case of HEV infec-tion person-to-person transmission is also an important factor in sporadic cases [3]. Outbreaks of HAV and HEV are therefore manifestations of the poor sanitation practices and lack of clean water supplies often found in developing countries. Humanitarian crises with large refugee populations can also be fertile ground for hepatitis outbreaks alongside cholera or other waterborne outbreaks, as was recently seen among Syrian refugees in Iraq [4]. Understanding the importance of the risk of hepatitis outbreaks in displaced populations can help in identifying out-breaks quickly and responding to them in a timely manner to reduce mortality and morbidity. HAV has 7 genotypes, with little variation in their clinical expression. HEV has 4 genotypes with quite differ-ent clinical expressions, responsible for different disease manifestations across developing and developed countries. In developing countries genotype 1 is largely responsible for outbreaks and sporadic cases, via contamination of water and the fecal–oral route. Excep-tions include Mexico in South America and countries in Africa, where genotype 2 is more common [5]. Neither HAV nor HEV have chronic states, although HEV is reported in immunocompro-mised people [6]. Acute HAV infection is often clini-cally indistinguishable from other caus-es of acute viral hepatitis, and laboratory confirmation is necessary. Diagnosis of HEV has its own challenges, which may result in an underestimation of the disease burden [6]. HAV has a very effective vaccine available, and the first vaccine for HEV was approved in China in December 2011, although it is not yet used in any other countries. Whereas HAV seroprevalence increases with age and comes close to 100% in highly endemic countries by the age of 5 years, HEV seroprevalence tends to stay be-tween 5%–60% [7]. In 2010, the WHO World Health Assembly adopted resolution WHA63.18, which called for the pre-vention and control of viral hepatitis, with a focus on HBV and HCV [8]. This resolution came after Member States and WHO understood the gravity of spread of viral hepatitis. In 2012, on the occasion of World Hepatitis Day, Dr Ala Alwan, WHO Regional Director for the Eastern Mediterranean, urged all stakeholders to combine their efforts to confront and combat this silent epi-demic of hepatitis. Many countries of the Eastern Mediterranean Region (EMR) are cur-rently going through major social and political upheavals. With active or proxy wars engulfing many countries in the Region, the public health structures are under stress, creating ideal conditions for the spread of all infectious diseases, especially those spread by contaminated water and lack of sanitation services. Except for a few published articles and outbreak reports, however, very limited data are available about the prevalence of HAV and HEV from these countries or from the Region in general [9–12]. One major reason for this knowledge gap is that we are not looking for the evidence. In most developing countries, including most of those of the EMR, HEV is not routinely considered when a physician asks for investigations into a suspected case of viral hepatitis. Added to the diagnostic challenges is the fact that a majority of hepatitis-infected per-sons do not develop an acute condition that requires major health care interven-tion. HAV is in the same class, with few symptomatic cases reaching health-care settings, and as it is self-limiting in most cases, it is neither investigated nor re-ported to surveillance systems as HAV. Physicians also do not consider HAV or HEV to be serious illnesses, even though fulminant hepatitis, hepatic failure and death can occur from both infections.More than 40% of the population of the EMR lives in just 2 countries, Egypt and Pakistan, both of which are consid-ered endemic for HBC and HCV [8]. In Pakistan, the Field Epidemiology Labo-ratory Training Programme is collecting information about acute viral hepatitis cases via 5 sentinel sites throughout the country [13]. According to reports from the Pakistan viral hepatitis surveillance system HAV—responsible for more

Hepatitis E virus (HEV) infection is known to run a self-limited course. Recently, chronic hepatitis E has been described in several immunosuppressed patients after solid organ transplantation. The prevalence of HEV infection after transplantation, however, is unknown. We studied HEV parameters [HEV RNA, HEV immunoglobulin M (IgM), and HEV immunoglobulin G (IgG) by enzyme-linked immunosorbent assay and confirmatory immunoblotting] in a cohort of 285 adult liver transplant recipients. The most recent freeze-stored sera were investigated, and if they were positive, a retrospective analysis was performed. Samples from 274 patients (96.1%) tested negative for all HEV parameters. This included a patient described earlier as having experienced an episode of chronic HEV hepatitis in the past. One patient was found positive for HEV RNA without HEV antibodies. She presently suffers from chronic HEV hepatitis and has also been described before. Sera from 9 patients tested positive for HEV IgG without HEV IgM or HEV RNA. Six of these 9 patients (2.1% of the total) were found to have HEV IgG antibodies in retrospect related to an HEV infection at some time pre-transplant as they also tested positive in a pretransplant serum sample. One of these 9 patients suffered in retrospect from a chronic HEV infection with mild hepatitis between 2 and 5 years after liver transplantation on the basis of the course of HEV RNA, IgM, and IgG, aminotransferases, and liver histology. Overall, the prevalence of acquired HEV hepatitis after liver transplantation was 1% in this cohort. We conclude that liver transplant recipients have a risk for chronic HEV infection, but the prevalence is low.

Objective: To estimate the seroprevalence of enteric transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients presented with acute viral hepatitis in a tertiary care hospital, Delhi. Methods: It was a retrospective study from February 2019 to December 2020 conducted in a tertiary care hospital, Delhi. Serum samples from clinically suspected hepatitis patients sent for HAV and HEV testing were included in the study. The samples were tested for HAV and HEV Immunoglobulin (Ig)M antibody by enzyme-linked immunosorbent assay. Data collected in Excel sheet were analyzed using SPSS software version 21. Chi-square and Fischer exact test were used wherever necessary. Results: Viral etiology (HAV or HEV) was found in 122 (18%) patients. IgM HAV was detected in 75 (11%) patients whereas IgM HEV in 47 (7%) patients. The coinfection of HAV and HEV was not observed. HAV infection was significantly more common in pediatric age group 32.8% (59/180; P

Seroprevalence of Hepatitis A and E Viruses Based on the Third Korea National Health and Nutrition Survey in Korea

Hepatitis E virus serum antibodies and RNA prevalence in patients evaluated for heart and kidney transplantation

Background and Objectives: Hepatitis A and E present significant public health dilemmas contributing to high morbidity and mortality rates, particularly in developing nations. Both viruses spread through the fecal-oral route, resulting in a range of symptoms, from asymptomatic infections to severe acute viral hepatitis (AVH). Given the seriousness of these pathogens and the scarcity of available data, we undertook this study to determine the seroprevalence, epidemiological patterns, seasonal changes, and instances of coinfection involving hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients with AVH. Methods: This retrospective study was conducted in a tertiary care hospital located in North India. Blood samples from patients exhibiting symptoms consistent with AVH were analyzed for anti-HAV and anti-HEV immunoglobulin M (IgM) using commercially available enzyme-linked immunosorbent assay (ELISA) kits. A total of 3,363 patient samples were analyzed. Results: The ELISA for anti-HAV IgM yielded a positivity rate of 20.3%, while only 0.6% tested positive for anti-HEV IgM. Among those with positive HAV serology, 41.2% were under 10 years old, followed by 30.9% in the 11–20-year age cohort. Conversely, the majority of HEV-positive cases (47.6%) were found within the 21–30-year age group. Both viruses demonstrated a marked increase during the winter and monsoon seasons. There is a higher seroprevalence of hepatitis A as compared to hepatitis E, and a seasonal surge in both cases was seen in this region of Northern India during the monsoon and winter months. Conclusion and Implications for Translation: The diagnosis of acute viral hepatitis (AVH) requires serological validation to identify viral agents, revealing high seroprevalence of hepatitis A in Northern India with seasonal increases during monsoon and winter. Coinfections with hepatitis A (HAV) and E (HEV) are low, but their implications need further study. Public health strategies should focus on safe drinking water access, improved sewage systems, hygiene education, routine HAV immunization, and efficient outbreak detection to reduce morbidity and prevent epidemics in high-risk areas.

Objectives: Hepatitis A virus (HAV) and Hepatitis E virus (HEV) both are spread through the fecal-oral route and cause acute viral hepatitis (AVH) and pose a major public health problem in India. This study was done to find out the proportion of positivity of HAV and HEV in patients with AVH and its seasonal trend. Materials and Methods: A retrospective study was carried out at Surat Municipal Institute of Medical Education and Research Medical College, Department of Microbiology, Surat, Gujarat. Result of 3615 blood samples of suspected AVH patients of the past 5 years (January 2018–December 2022) were taken from hospital data records. The enzyme-linked immunosorbent assay method was used to test serum samples for immunoglobulin M (IgM) HAV and IgM HEV antibodies for HAV and HEV, respectively. All samples were evaluated for liver function as well. Results: The positivity of HAV and HEV was 15.13% and 10.26%, respectively. The coinfection rate was 2.07%. HAV and HEV both affected males more than females. Among pregnant females, HEV infection had more positivity (6.77%) than HAV, which had 1.08% positivity. HAV and HEV infections had a seasonal trend, with the highest infection rate in the monsoon. Conclusion: The declining trend of cases of HAV and HEV was found in Surat city of south Gujarat which indicates increased awareness about hepatitis among people and better public health management by the civic authorities.

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P &lt; 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden.

Hepatitis E virus superinfection in patients with chronic liver disease

Hepatitis E virus (HEV) infections are a major cause of acute hepatitis in developing and industrialized countries. Little is known about anti-HEV immunity in solid-organ recipients. We screened 263 solid-organ recipients for anti-HEV immunoglobulin G (IgG) at transplantation. They were followed up for 1 year and tested for HEV RNA and anti-HEV antibodies 1 year after transplantation and if their liver enzyme activities increased. A total of 38.4% had anti-HEV IgG at transplantation. The mean concentrations (±SD) of anti-HEV IgG at transplantation (8 ± 17.5 U/mL) and 1 year later (6.4 ± 12.0 U/mL, P = .4) were similar. There were 3 de novo HEV infections during the 1-year follow-up among patients who were HEV seronegative before transplantation, giving an annual incidence of 2.1%. We also identified 3 HEV reinfections among patients who were seropositive before transplantation through detection of HEV RNA, for an annual incidence of 3.3%. Their anti-HEV IgG concentrations were 0.3, 2.1, and 6.2 World Health Organization (WHO) units/mL before transplantation. Reinfection of the patient with the lowest IgG concentration at transplantation had evolved to a chronic infection. Low anti-HEV antibodies (<7 WHO units/mL) seemed not to protect solid-organ recipients. HEV reinfection in immunocompromised patients can lead to chronic infection, as in primary infections.