anti-HEV IgM Research Articles

IL-18 discriminates highly frequent hepatitis E virus positive from negative blood donors in Mexico

Introduction and ObjectivesHepatitis E virus (HEV) is not routinely screened in blood banks in low- and middle-income countries, and no specific biomarkers of exposure to this virus have yet been identified. We aimed to identify HEV seropositivity and detect virus RNA among blood donors from Mexico to further correlate risk factors related to infection and levels of interleukin-18 (IL-18) and interferon-gamma (IFN-γ) as potential biomarkers. Materials and MethodsThis cross-sectional, single-center study included 691 serum samples of blood donors obtained in 2019. Anti-HEV IgG and IgM antibodies were detected in sera and the viral genome was screened in pooled samples. A statistical comparison of risk factors for infection, demographic and clinical features was performed; IL-18 and IFN- γ values were tested in sera. ResultsOf all the individuals, 9.4% were positive for anti-HEV antibodies and viral RNA detection was confirmed in one of the pools positive for anti-HEV. From the analysis of risk factors, age and having pets were statistically significant for anti-HEV antibody detection. Seropositive samples showed significantly higher IL-18 concentrations relative to samples from seronegative donors. Interestingly, IL-18 values were similar when HEV seropositive samples were compared to samples from clinically acute previously confirmed HEV patients. ConclusionsOur findings highlight the need to follow up on HEV in blood banks in Mexico and underscore that IL-18 could represent a biomarker of HEV exposure.

Frequency, Clinical Presentation, and Outcome of Acute-on-chronic Liver Failure among Decompensated Cirrhosis of Liver Patients in a Tertiary Care Hospital

Background: Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. Different international entities have taken initiatives to define the condition in different times but recommendations and definitions from The European Association for the Study of the Liver- Chronic Liver Failure (EASL-CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study are most comprehensive and widely accepted till date. Only limited data are available on the prevalence, clinical characteristics, and short-term outcomes of ACLF in Bangladesh. It would be very useful for clinicians to identify patients with ACLF early and initiate focused therapy including referral to transplant centers if these data are available. Objective: To evaluate frequency, clinical presentation, and outcome of acute-on-chronic liver failure among decompensated cirrhosis of liver patients. Methods: This prospective observational study was carried out at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD), BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh from July, 2019 to September, 2021. Total 175 patients with decompensated cirrhosis of liver were screened, out of which 22 patients dropped out due to various reasons. Purposive type of non-probability sampling technique was used. Formal ethical clearance was taken from the IRB and ethical measures were ensured in concordance with the Declaration of Helsinki. An informed written consent was taken from all participants. Diagnosis of decompensated cirrhosis was based on clinical, biochemical, radiological and endoscopic findings. Laboratory data sent within 24 hours were collected. Oxygen saturation was measured using fingertip pulse oximeter. Investigations for ACLF triggers were done as necessary which included but not limited to urine routine and microscopic examination, urine culture, blood culture, and Anti HEV IgM. Patients’ prognosis and survivability were observed by follow up phone call at 30 days. All data were recorded in a separate case record form and finally, it was analyzed by SPSS 23. Results: Out of 153 patients, 49 patients (32%) had ACLF: grade 1 ACLF in 26 (17%), grade 2 in 18 (11.8%), and grade 3 in 5 (3.3%) patients. Patients had an average age of 59.54±11.55 years with no significant difference between ACLF and no ACLF groups. Most patients in both groups had others (NAFLD, autoimmune hepatitis, secondary biliary cirrhosis, none) as the main underlying cause of cirrhosis. Bacterial infection, GI bleeding, HEV infection, reactivation of HBV were the precipitating events in 81.6% of patients with ACLF, with bacterial infection being the most common trigger (63.3%). Overall, 44.9% ACLF patients died within 30 days of admission. Older age, male sex, hepatic encephalopathy, GI bleeding, presence of any trigger and higher CTP score were associated with increased risk of death in ACLF. Conclusion: Follow up of 153 patients with decompensated cirrhosis of liver revealed that 1 in 3 patients had ACLF and 44% of them would die in 30 days. Bacterial infection and GI bleeding were the most common triggers of ACLF. Early identification and intervention with multidisciplinary approach and referral to transplant centers are likely to improve survival outcomes in this population. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 221-222

Laboratory diagnosis of hepatitis type E

Hepatitis type E virus (HEV) infection is a common cause of acute viral hepatitis in China, and its etiological diagnosis relies on laboratory detection. Therefore, this article introduces the HEV RNA, HEV antigen, anti-HEV IgM, and IgG detection methods and their diagnostic application value. In addition, it also discusses the current international diagnostic standard and HEV infection presentation.

The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection—A Condition Affecting Immunocompromised Patients

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7—usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments—such as ribavirin—should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.

Aggravating Effects of Hepatitis E Virus Infection on Patients with Chronic Liver Disease in Ibn-Sina Hospital Sudan

Background: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. Sudan is considered as hyper-endemic for HEV. HEV infection in patients with preexisting chronic liver diseases (CLDs) has been reported to result in severe clinical manifestations and poor outcomes. However data on the role of HEV infection in worsening of pre-existing CLD are limited.
 Objective: To determine hepatitis E virus (HEV) infection and its effect on severity of CLD.
 Methods: A descriptive cross-sectional study that consecutively enrolled 87 CLD patients in Ibn-Sina Specialized Hospital was carried out during the period from August 2020 to December 2020. Data regarding demographics, CLD causes, clinical manifestations and comorbidities were collected. The screening for anti-HEV antibodies was performed in all patients by using enzyme linked immuno-sorbent assay (ELISA).
 Results: Hepatitis B virus (HBV) was the commonest etiology of chronic liver diseases being detected in 45/87(51.7%) patients. On the other hand;among all subjects; 43/87(49.4%) patients were HEV seropositive with anti-HEV Ig-G being detected in 32(36.8%) and concurrent anti-HEV Ig-M and Ig-G in 11(12.6%) patients. Jaundice (OR= 3.8, CI95%: 1.5-9.4; P. value=0.004), HCC (OR= 4.1, CI95%: 1.4-11.9; P. value=0.008), child-Pugh class-C (OR= 26, CI95%: 5.4-94.0; P. value=0.000) and child-Pugh class-B (OR= 5.3, CI95%: 1.6-17.0; P. value=0.000) were associated independently with anti-HEV positivity.
 Conclusion: The frequency of hepatitis E virus (HEV) among Sudanese patients with chronic liver disease (CLD) was considerably high (mainly past infection- Ig-G). Furthermore, HEV was associated with advanced liver failure statuses (child-Pugh class-B & C), jaundice, and hepatocellular carcinoma.

Seroepidemiology of Hepatitis E virus among the voluntary blood donors in the coastal region of Karnataka, India

Background: Hepatitis E is a fecal orally transmitted disease and an emerging transfusion transmissible infection with potential transfusion safety implications. Hepatitis E Virus screening among blood donors is not routinely done despite the fact that it is endemic in India. As there are very few reports and evidence, the justification for mandating HEV screening among blood donors is still only marginally convincing. Therefore, the present study was carried out to determine the incidence and prevalence of HEV infection among blood donors in Coastal Karnataka, India. Methods: This cross-sectional study was conducted in a tertiary care hospital in Udupi district of Karnataka, India. A total of 1939 blood donors were randomly selected between June 2020 to June 2022 to participate in the study, where anti-HEV IgM antibody screening was performed using HEV IgM ELISA test kit (DiaPro, Italy). Further, a randomly selected 588 and 1620 pooled donor samples were screened for anti-HEV IgG antibodies and HEV RNA, respectively. Results: The overall prevalence of HEV IgM antibodies among study application is found to be 1.39%, with a statistically significant difference between males and females (n=20, 1.18% vs. n=7, 3.07 %; p=0.027). The prevalence of HEV IgG antibodies was 11.39%. Exposure to agriculture, animal husbandry, and poor hand hygiene were significant risk factors for HEV IgG reactivity. Conclusions: Given the high prevalence of HEV viral markers in the study population, routine screening of blood donors for risk factors and implementation of serologic testing in endemic areas may be considered.

Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States

BackgroundHepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012. MethodsHEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection. ResultsOut of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81–57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04–0.90; p = 0.046). ConclusionKTRs who had HEV infection may be at an increased risk of developing chronic HEV.

Prevalence of Hepatitis A Virus and Hepatitis E Virus in a tertiary care hospital, East Delhi, India.

Background & Aim: Acute viral hepatitis (AVH) is a condition that is known to be caused by enterically transmitting Hepatitis A virus (HAV) and Hepatitis E virus (HEV). Usually, they result in self-limiting disease but can be seriously threatening if complications arise. This study was done to determine the prevalence rate of HAV and HEV in a tertiary care hospital in East Delhi, India.
 Material & Methods: The retrospective and observational study of 2-year duration was conducted in the Department of Microbiology at UCMS and GTBH Delhi, India. A total of 410 samples from patients presenting with a clinical diagnosis of acute hepatitis were considered in the study. The serum samples were analysed for IgM anti-HAV and IgM anti-HEV, respectively, using commercially available ELISA kits.
 Results: The seroprevalence of HAV and HEV were 2.19% and 0.24%, respectively. No case was found to be reactive for both parameters, indicating no case of co-infection. The majority of clinical samples were from female patients.
 Conclusion: The incidence of HEV and HAV illnesses suggests that East Delhi has a lower prevalence rate of the reported viral illnesses. This finding suggests one of the following: limited circulation of the agents, good sanitary conditions, and/or protective immunity among the population tested. Nonetheless, we should continue to assess the ongoing conditions and take measures to improve them.

Seroprevalence of hepatitis E virus after pediatric liver transplantation.

Southeast Asia is the endemic area of hepatitis E virus (HEV) infection. We aimed to determine the seroprevalence of the virus, its association, and the prevalence of chronic infection after pediatric liver transplantation (LT). A cross-sectional study was performed in Bangkok, Thailand. Patients aged <18 years who had LT for >2 years underwent serologic and real-time polymerase chain reaction (rt-PCR) tests. Acute HEV infection was defined by the presence of positive anti-HEV immunoglobulin (Ig)M and HEV viremia from the rt-PCR. If the viremia persisted for >6 months, chronic HEV infection was diagnosed. A total of 101 patients had a median age of 8.4 years [interqartile range (IQR): 5.8-11.7]. The seroprevalence of anti-HEV IgG and IgM was 15% and 4%, respectively. Positive IgM and/or IgG were associated with a history of elevated transaminases with an unknown cause after LT (p = 0.04 and p = 0.01, respectively). The presence of HEV IgM was associated with a history of elevated transaminases with an unknown cause within 6 months (p = 0.01). The two patients (2%) diagnosed with chronic HEV infection did not fully respond to the reduction of immunosuppression but responded well to ribavirin treatment. Seroprevalence of HEV among pediatric LT recipients was not rare in Southeast Asia. Since HEV seropositivity was associated with elevated transaminases of an unknown cause, investigation for the virus should be offered in LT children with hepatitis after excluding other etiologies. Pediatric LT recipients with chronic HEV infection may receive a benefit from a specific antiviral treatment.

Prevalence of HIV and Viral Hepatitis Markers among Healthcare Workers in the Republic of Guinea.

Healthcare workers are much more likely to be infected with HIV and hepatitis viruses compared to the general population. Although healthcare workers are more aware of HIV and hepatitis viruses, several countries in Africa lack a comprehensive grasp of disease routes and transmission risks. The aim of this study was to assess the prevalence of the serological and molecular biological markers of HIV and viral hepatitis among healthcare workers in the Republic of Guinea. The study material was 74 blood serum samples collected from healthcare workers who received additional training at the Institute of Applied Biological Research of Guinea (IRBAG, Kindia, Republic of Guinea). The markers examined included HBsAg, HBeAg, anti-HBs IgG, anti-HBcore IgG, anti-HCV qualitative determination, anti-HEV IgM and IgG, anti-HAV IgM and IgG, and anti-HIV. For viral DNA and RNA detection, nucleic acids were extracted from blood serum, and viral presence was inferred using real-time PCR with hybridization fluorescence detection. A high prevalence of viral hepatitis B markers was shown, and significantly fewer cases of viral hepatitis C and HIV were detected. Almost all examined medical workers had anti-HAV IgG antibodies, but no antibodies to hepatitis E virus. Apparently, the identified markers depend on the general prevalence of certain pathogens in the region and are associated with the traditions and characteristics of the country's residents.

Prevalence of Hepatitis E Virus in Patients with Chronic Hepatopathy in a Reference Center of Bahia State, Brazil

Introduction: Hepatitis E virus infection can lead to severe liver disease and unregulated hepatitis in patients with a history of previous chronic liver disease of different etiologies. Objective: To determine the seroprevalence of hepatitis E in untreated carriers of hepatitis C virus, hepatitis B virus, autoimmune hepatitis and in patients with drug-induced liver disease. Materials and Methods: This is a cross-sectional study with a total sample of 301 outpatient hepatology volunteers. The detection of anti-HEV IgM and IgG antibodies was determined using the ELISA (RecomWell anti-HEV IgG and IgM, Mikrogen®, Germany), One-step real-time PCR was used for the detection of HEV-RNA (Taqman, Life Technologies TM, Foster City, CA, USA). Results: The overall prevalence of anti-HEV IgG and IgM in the population studied was 12.95% and 2.3%, respectively. The prevalence by group were: anti-HEV IgG: hepatitis C virus with 13.2%, hepatitis B virus with 13%, autoimmune hepatitis with 8.1 and drug-induced liver disease with 21.1. Patients with HCV chronic hepatitis and positive HCV IgG serology showed an increase in transaminase levels in 66.7% (10/15) of the cases, while in the seronegative patients this increase was present in 42.4% (42/99) of the cases (p&lt;0.05). Conclusions: A high seroprevalence of HEV was observed. Among the patients with serology concomitantly positive for anti HEV IgG and IgM, 57.1% (4/7) had higher levels of TGO and TGP, suggesting acute HEV infection. A relationship between hepatitis C and E virus co-infection and elevated transaminase levels has been demonstrated. Future studies with evaluation of several clinical parameters are necessary.

Hepatitis E virus seroprevalence among employees in catering and public place industries in Nanjing, China.

This study aimed to assess the prevalence of anti-hepatitis E virus (HEV) immunoglobulin (Ig) M and elevated serum alanine aminotransferase (ALT) levels among employees in catering and public place industries. Blood samples were collected between January and December 2020 from 26,790 employees working in the Qinhuai district of Nanjing, China. Anti-HEV IgM in the serum samples was tested by the capture ELISA method and ALT was tested by the IFCC method. Samples positive for anti-HEV IgM or with ALT levels over 200U/L were subjected to PCR screening of HEV RNA. The overall seroprevalence of anti-HEV IgM was 0.41%, and the seroprevalence was slightly higher in males (0.47%) than in females (0.37%); however, the difference was not substantial (p=0.177). Seroprevalence of anti-HEV IgM increased with age, reaching its peak level after 48years of age. The prevalence of elevated ALT levels was 4.24%, and males exhibited a higher prevalence than females (6.78% vs 2.65%, p<0.001). Prevalence of elevated ALT levels differed in age groups and the 26-36-year-old group had the highest rate of elevated ALT levels. Employees with elevated ALT levels had a higher prevalence of positive anti-HEV IgM than those with normal ALT (0.57% vs 0.31%, p<0.001). Positive HEV RNA was detected in one anti-HEV IgM-negative employee with ALT higher than 200U/L. In our study, all the HEV RNA-positive and IgM-positive individuals are asymptomatic, and a combination of ALT tests, serological methods, and molecular methods is recommended to screen asymptomatic HEV carriers and reduce the risk of transmission.

Prevalence of hepatitis E virus and its association with adverse pregnancy outcomes in pregnant women in China.

Hepatitis E virus (HEV) infection has become a global concern, especially in pregnant women. However, the association between HEV prevalence and age, gravidity and parity of pregnant women remains unclear. Pregnant women (n=19,762) were enrolled for HEV prevalence and associated adverse pregnancy outcomes investigation in Qujing City, Yunnan Province of China from May 2019 to December 2020. The seroprevalence of HEV was 11.6% (2,297/19,762; 95% CI:11.2%-12.1%). About 11.4% (2,247/19,762; 95% CI:10.9%-11.8%) were positive for anti-HEV IgG antibody, 0.1% (22/19,762; 95% CI:0.1%-0.2%) were positive for anti-HEV IgM antibody, and 0.1% (28/19,762; 95% CI:0.1%-0.2%) were positive for both anti-HEV IgM and IgG antibodies. Sixty-one out of 2,297 anti-HEV-antibodies-positive pregnant women were positive for HEV RNA. Phylogenetic analysis revealed that all HEV isolates from pregnant women belong to genotype 4. Age, gravidity and parity are associated with increased prevalence of HEV. Pregnant women positive for HEV-IgG antibody bear a higher risk for an adverse pregnancy history and liver injury with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than anti-HEV-negative pregnant women. Furthermore, seropositive pregnant women suffered a higher adverse maternal outcomes risk (crude odds ratio [cOR]=1.29; 95% CI: 1.16-1.43; adjusted odds ratio [aOR]=1.40, 95% CI: 1.25-1.55 for anti-HEV-IgG-positive pregnant women and cOR=1.38, 95% CI: 1.02-1.86; aOR=1.43, 95% CI: 1.05-1.95 for anti-HEV-IgM-positive pregnant women) and fetal outcomes risk (cOR=1.80, 95% CI: 1.61-2.01; aOR=1.77, 95% CI: 1.57-1.99) than anti-HEV-negative pregnant women. Adverse pregnancy outcomes of HEV infection are aggravated by age, gravidity and parity. In this study, we demonstrated high prevalence of HEV in pregnancy women in China, and HEV infection can cause various adverse maternal and neonatal outcomes.

Application of a truncated ORF2 protein-based ELISA for diagnosis of hepatitis E in an endemic area.

Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis depends on detection of specific IgM antibodies in serum. Present study evaluated performances of two in-house and six commercial IgM detection enzyme-linked immunosorbent assays (ELISAs) using sera collected from volunteers/acute hepatitis patients (n = 716). The in-house ELISAs were based on complete and truncated open reading frame 2 (ORF2) proteins containing neutralizing epitope/s region of genotype 1 HEV (ORF2p, 1-660 amino acid (a.a.) and T1NEp, 458-607 a.a., respectively). The commercial ELISAs included Wantai (China), MP Diagnostics (MPD) (Singapore), DIA.PRO Diagnostics (Italy), MBS (Italy), abia (Germany), and ImmunoVision (USA). T1NE ELISA showed 97.0% positive percent agreement (PPA), 99.4% negative percent agreement (NPA), and 98.6% concordance (κ = 0.97, P = 0.0000) with ORF2 ELISA. ORF2, T1NE, Wantai, and MPD ELISAs agreed on results for 88% of sera tested. Two percent sera showed reactivity in each combination of three and two of aforementioned four ELISAs. Remaining 8% sera were single ELISA reactive. PPA and NPA value ranges were 76.3-99.0% and 84.8-99.5%, respectively. Pairwise concordances between all the eight ELISAs ranged from 88.0 to 100% (κ: 0.74-1.00). Both the in-house ELISAs agreed better with Wantai over MPD ELISA. In conclusion, both ORF2 and T1NE ELISAs were equally efficient in diagnosing HEV infections. T1NEp proved to be an excellent tool in HE sero-diagnosis and is worth exploring in development of simple rapid tests. KEY POINTS: • In-house ELISA based on bacterially expressed neutralizing epitope/s region protein • In-house ELISA based on complete ORF2 protein expressed in insect cells • Comparison of two in-house and six commercial anti-HEV IgM antibody detection ELISAs.

Hepatitis E Virus Infection, a Risk for Liver Transplant Recipients in Sweden.

During 2013 to 2015, 109 of 152 prospectively enrolled patients listed for LT received a liver graft and completed the study protocol. They were evaluated for anti-HEV IgM, HEV IgG, and HEV RNA at the time of LT assessment and 3 and 12 mo post-LT. Medical records were reviewed. Twelve (11%) LT recipients acquired markers of HEV infection during the study period. Seven patients (6%) had detectable HEV RNA, 1 before LT and 3 at the 3-mo and another 3 at the 12-mo follow-up post-LT. All resolved their infections without treatment and had undetectable HEV RNA at the succeeding follow-up. Another 5 (5%) patients developed anti-HEV antibodies without detectable HEV RNA as an indication of HEV infection during follow-up. Signs and symptoms of HEV infection were subtle' and none were diagnosed in routine clinical care. A substantial proportion of LT recipients in Sweden are at risk of acquiring HEV infection, both before and after LT. The results highlight the frequency of silent, spontaneously resolving HEV infections and do not support universal screening of LT recipients in Sweden, despite HEV being a potentially treatable infection.

Hepatitis E infection in adults with primary immunodeficiency with or without immunoglobulin replacement therapy.

In a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease. We investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG. Three of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p<0.001). Anti-HEV IgG were detected in all batches of immunoglobulin preparations, although the titer varied from 3 to 127 IU/g IgG. Seroconversion was observed in 15 of the 22 (68%) patients tested before and after IgRT. No cases of chronic HEV-related disease were detected among patients with primary immunodeficiency and hypogammaglobulinemia, whether they received IgRT or not. This confirms that patients with primary immunodeficiency have a low risk of chronic infection despite a seroprevalence close to that observed in the French general population and that IgRT, which confers a high HEV seroprevalence, might play a key role in protection against chronic infection.

Profile of clinical characteristics and serologic markers of sporadic hepatitis E in a community cohort study

ABSTRACT Hepatitis E virus (HEV) is a pathogen of global significance, but the value of HEV-related markers in the diagnosis of hepatitis E remains controversial. Previous studies on hepatitis E profiles have been mainly cross-sectional and conducted among inpatients in large hospitals, and hepatitis E cases have been primarily defined by limited partial markers. In this community-based study, 4,110 active hepatitis cases from a population of nearly 600,000 were followed over 48 months and serial serum samples were collected. Both HEV pathogen (HEV RNA and antigen) and anti-HEV antibody markers were used to determine HEV infection status and the relationship between hepatitis and HEV infection. In total, 98 hepatitis E patients were identified and all available isolates from 58 patients belonged to HEV genotype 4. The mean age of the patients was 58.14 years, with an overwhelming proportion of males (70.4%). Hepatitis E accounted for 22.86% of active hepatitis cases with alanine aminotransferase levels ≥15.0-fold the upper limit of normal, suggesting the need to include HEV in routine testing for these patients. Ninety-two hepatitis E patients were positive for at least 2 of HEV antigen, anti-HEV IgM, and HEV RNA markers at presentation, and 90.22% of them were positive for HEV antigen and anti-HEV IgM. HEV antigen, HEV RNA, and anti-HEV IgM positivity were observed in 89.80%, 82.65%, and 93.88% of hepatitis E patients at presentation, respectively. However, only 57.14% of anti-HEV IgM positivity occurred in hepatitis E patients. These findings will advance our understanding of hepatitis E and improve diagnosis.

Status of anti-HEV IgG and IgM antibodies among the hemodialysis patients in southwest region of Iran.

Hepatitis E Virus (HEV) account for acute hepatitis, fulminant liver failure and chronic hepatitis worldwide. Several high risk groups including hemodialysis (HD) patients are at risk of HEV infection. Based on consequences of HEV infection it is important to determine the serological and molecular epidemiology of HEV in HD patients. The aim of this study was to evaluate the frequency of HEV antibodies and HEV RNA in HD patients. The sera of 84 HD patients were collected and tested for anti-HEV IgG and anti IgM antibodies using enzyme-linked immunosorbent assay (ELISA) at Golestan hospital in Ahvaz city during October 2014 and November 2014. HEV RNA was tested in HD patients using RT PCR. The prevalence of anti-HEV IgG was evaluated in the age group (52/84) > 50 and (31/84) < 50 years. Out of 84 patients, 52 (61.9%) were males and 32 (38.1%) females. The mean age of participants was 52 ± 1.57 years. 43/84 (51.19%) cases including 26/52 (50%) males and 17/32 (53.1%) females were positive for anti-HEV IgG (p=0.95). Among the 43 cases positive anti-HEV IgG 8 cases including 5 (9.61%) males and 3 (9.37%) females tested positive for anti-HEV IgM (p=0.729) while the HEV RNA was negative in HD patients. The distribution of anti-HEV IgG was 62.75% and 33.33% among the age group >50 and <50 respectively (p=0.015). This study showed high prevalence of anti-HEV IgG antibodies (51.19%) were observed among the HD patients while the HEV RNA tested negative in HD patients. The rate of HEV IgG is significantly higher with increased age. Further investigation require to identify the factors account for high seroprevalence of HEV in Ahvaz HD units.

Characteristics of hepatitis E viral infections in Hungary.

Hepatitis E virus (HEV) is one of the most important causes of hepatitis worldwide. Despite this, limited data published more than ten years ago are only available about HEV epidemiology in Hungary. We aimed to determine the epidemiological features of HEV infections among patients submitted to various departments of our university hospital in Hungary with signs and symptoms referring to acute hepatitis. One thousand four hundred thirty-one sera samples from 1,383 patients were analyzed by enzyme-linked immunosorbent assays (ELISA). In some patients, HEV RNA was detected by broad-range nested polymerase chain reaction (PCR) if acute hepatitis was confirmed. PCR products were sequenced and compared with other available sequences in GenBank. Five hundred eighteen sera from 429 patients proved positive (31.0%) for HEV-specific immunoglobulin G (IgG) with a mean age of 60.0 years. Most sera with anti-HEV IgG antibodies were collected from adults and elderly patients. Anti-HEV IgM positive results were found in the case of 95 sera samples from 70 patients (5.1%). Acute HEV infections were confirmed mostly over 40 (n=67, 95.7%). The number of males (n=47, 67.1%) was higher than females (n=23, 32.9%). We detected HEV-specific PCR products in seven patients (10.9%). Genotyping was successful for 5 out of 7 PCR-positive samples. All sequences belonged to genotype 3 (subgenotypes: e, f). In our survey, we confirmed the constant presence of acute HEV infections in Hungary and an increased seroprevalence of anti-HEV IgG antibodies compared to a previous study.

Calibrating Hepatitis E Virus Serological Assays Using Asymptomatic Specimens Obtained in Japan.

ABSTRACTThis study aimed to calibrate hepatitis E virus (HEV) serological assays. We optimized the previously developed in-house HEV antibody enzyme-linked immunosorbent assay (ELISA) by setting the cutoff with an in-house serological performance panel consisting of broad HEV antibody titers and subtracting nonspecific background values for anti-HEV IgM, IgA, and IgG. We also compared the assay’s performance with that of commercial serological assay kits (four kits for IgM, one for IgA, and two for IgG). Although all serological assays readily detected HEV antibodies at high titers in the symptomatic hepatitis E population, considerable variations between assays were observed in the asymptomatic population. The in-house ELISA showed a higher sensitivity for HEV IgM, IgA, and IgG than the commercial kits and detected the seroconversion of HEV IgM and IgG earlier when testing a commercially available HEV seroconversion panel. The low sensitivity of the commercial kits was due to the high setting of the original cutoff, which was demonstrated by receiver operating characteristic analysis. However, the corrected cutoff value reduced assay specificity. Background subtraction is essential to achieve high specificity because the in-house ELISA without background subtraction reduced its specificity. These results indicate that asymptomatic specimens and background subtraction contribute to the optimization of HEV serological assays.IMPORTANCE Accurate diagnosis of hepatitis E virus (HEV) infection is essential for public health surveillance and for preventing HEV-contaminated blood transfusion. Anti-HEV IgM or IgA is used as a reliable marker of recent HEV infection. However, considerable variability in the sensitivity and specificity of HEV antibody detection is observed among several commercially available assay kits. In addition, none of the HEV antibody detection methods have been approved by the U.S. Food and Drug Administration (FDA). Here, we show that the in-house enzyme-linked immunosorbent assay (ELISA) could detect HEV IgM and IgA more sensitively than commercial kits in the asymptomatic population. We also suggest that the assay performance of commercial kits might be improved by optimizing the cutoff and reducing nonspecific background noise. A sensitive serological (IgM or IgA) assay in addition to HEV RNA testing will contribute to accurate diagnosis of acute HEV infection because HEV RNA-positive duration is relatively short.