Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area

AIM: To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally. METHODS: We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions. RESULTS: In our retrospective study, markers of acute HEV infection (IgM anti-HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71-54.70]). All 13 HEV-infected patients had been transfused at least once in a 3-month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti-HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti-HEV as well) and two of 25 control patients. Post-transfusion HEV infection developed in three of 22 susceptible (IgG anti-HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti-HEV positive (3/4). In contrast, none of the non-transfused patients developed HEV infection during the follow-up period. CONCLUSION: Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.     

Significance of serum IgA in patients with acute hepatitis E virus infection

AIM: To study the significance of serum anti-hepatitis E virus (HEV) IgA in patients with hepatitis E. METHODS: A new method was established to assay anti-HEV IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA. RESULTS: The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20±11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90±15 d and 120±23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA (P <0.05). CONCLUSION: The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.     

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

BackgroundIn a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease.Materials and methodsWe 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.ResultsThree 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.DiscussionNo 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.     

Anti-HEV IgG Avidity Testing: Utility for Diagnosing Acute and Resolved Genotype 3 Infections

European Association of the Study of the Liver (EASL) guidelines specify HEV RNA, as well as anti-HEV IgG and IgM as positive markers for acute HEV infection. HEV RNA assay sensitivity limitations may lead to false negative test results in patients with low levels of viremia. Moreover, anti-HEV IgM positivity is not a reliable indicator for distinguishing between acute and resolved infections given the ability of this antibody to persist several months after a resolved infection. Our study aims were to assess HEV IgG avidity for diagnosing acute and resolved infections, regardless of the anti-HEV IgM serostatus, and examine assay reliability when evaluating different genotype 3 (GT3) HEV subtypes. Patient serum samples (n = 104) were tested for HEV IgG avidity by utilizing the DIA.PRO kit on a DSX automated instrument. Among patients identified with acute HEV infections, 32 were infected with GT3: GT3c (n = 5), GT3e (n = 8), 3f (n = 17) and GT3-unsubtyped (n = 2). Avidity sensitivity was 91.2% and specificity was 100%. For patients with long-lasting anti-HEV IgM persistence, an Avidity Index >70% was observed. Thus, the DIA.PRO avidity assay may be utilized to distinguish between recently acquired and resolved HEV GT3 infections. However, for equivocal results (Avidity Index > 40–70%), HEV RNA molecular testing will be required to confirm a recent infection.     

Persistent Hepatitis E Virus Genotype 4 Infection in a Child With Acute Lymphoblastic Leukemia

Introduction:

In general, the hepatitis E virus (HEV) causes acute, self-limiting hepatitis. Prolonged and chronic infections caused by HEV genotype 3 have been found in some immunosuppressed patients in developed countries.

Case Presentation:

Here we report a Chinese boy with acute lymphoblastic leukemia, who developed hepatitis E during a period of intensive chemotherapy. Twenty months after the initial infection, HEV viremia was reappeared in the patient, with detectable anti-HEV IgM and IgG and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed the reactivation of the HEV genotype 4d strain, indicating viral persistence in the patient.

Conclusions:

To our knowledge, this is the first chronic case confirmed by the prolonged presence of HEV RNA in china. It is also the first reported persistent hepatitis E infection caused by HEV genotype 4.     

Detection of hepatitis E virus RNA and genotype in Bangladesh

Background/Aims:  Hepatitis E virus (HEV) in Bangladesh has not been adequately documented. We report HEV RNA and genotype detection in Bangladesh.
Methods:  In total, 82 samples were used; 36 sporadic acute hepatitis (AH), 12 fulminant hepatitis (FH), 14 chronic liver disease (CLD) and 20 from an apparently healthy population (HP) positive for both immunoglobulin (Ig) M and IgG specific anti-HEV antibodies (anti-HEV). The male/female ratio was 61/21, ages 12–67 (mean 30.4) years. RNA was extracted, transcribed to cDNA and amplified in nt 6345–6490 (ORF2) of HEV. Nucleic and amino acid sequences were determined. Homology comparison between Bangladesh clones and other representative HEV clones and phylogenetic tree analyses were done. Relations between HEV RNA-positivity and clinical factors were analyzed.
Results:  HEV RNA was positive in 9/36 (25.0%) of AH cases, 4/12 (33.3%) FH, 3/14 (21.4%) CLD and 0/20 (0%) HP samples; total 16/82 (19.5%). Four factors correlated significantly with HEV RNA-positivity (Mann-Whitney U test); alanine aminotransferase (ALT) ( P  = 0.0229), aspartate aminotransferase (AST) ( P  = 0.0448), and titers of IgG ( P  = 0.0208) and IgM ( P  = 0.0095) specific anti-HEV. The 16 HEV clones were divided mainly into two groups, A and B, including six different cDNA sub-groups.
Conclusion:  HEV RNA was found in sporadic AH and FH and sub-clinical CLD cases, but not in HP. HEV RNA-positivity was significantly related to values of ALT and AST and titers of IgG and IgM specific anti-HEV, with IgM specific anti-HEV showing the most significant relationship. All clones were genotype I, which is prevalent in South Asia.     

Characterization of Chronic Hepatitis E Virus Infection in Immunocompetent Rabbits

Chronic hepatitis E virus (HEV) infection is frequently reported in immunocompromised patients, but has also been increasingly reported in non-immunocompromised individuals. We characterized the course of chronic HEV infection in immunocompetent rabbits. In two independent experiments, 40 specific-pathogen-free rabbits were infected with a rabbit HEV genotype 3 strain in serial diluted titers (10⁸ to 10⁴ copies/mL). Serum and fecal samples were collected weekly and were tested for HEV RNA, antigen, anti-HEV and liver enzymes. Rabbits that spontaneously cleared the infection before 10 weeks post-inoculation (wpi) were kept to the end of the study as recovery control. Liver tissues were collected from HEV-infected rabbits at 5, 10 and 26 wpi for histopathological analysis. Nineteen rabbits (47.5%) developed chronic HEV infection with persistent viraemia and fecal HEV shedding for >6 months. Seroconversion to anti-HEV was observed in 84.2% (16/19) of the chronically infected rabbits. Serum levels of aminotransferase were persistently elevated in most of the rabbits. Characterizations of chronic HEV infection in immunocompetent settings could be recapitulated in rabbits, which can serve as a valuable tool for future studies on pathogenesis.     

急性戊型肝炎血清抗-HEV IgM、IgG和HEV RNA动态变化及其诊断价值

目的 分析急性戊型肝炎(AHE)患者血清抗-HEV IgM、抗HEV-IgG和HEV RNA变化规律。方法 2016年1月～2018年3月北京佑安医院就诊的AHE患者217例,动态检测血清抗-HEV IgM、抗HEV-IgG和HEV RNA变化。结果 首次检测血清抗-HEV IgM、IgG和HEV RNA均阳性31例(14.3%),抗-HEV IgM和IgG阳性99例(45.5%),抗-HEV IgM阳性8例(3.7%),抗-HEV IgG阳性72例(33.2%),抗-HEV IgM和HEV RNA均阳性3例(1.5%),抗-HEV IgG和HEV RNA均阳性2例(0.9%),抗-HEV IgM、IgG、HEV RNA均阴性2例(0.9%);在75例患者二次检测中,显示血清抗-HEV IgG阳性增多;在138例有准确的发病日期患者,在第1、2、3、4病周和第4病周后,血清HEV RNA阳性检出率分别为49.0%(25/51)、10.2%(6/59)、3.1%(1/32)、4.0%(1/25)和0.0%(0/0);血清抗-HEV IgM阳性检出率分别为70.6%(36/51)、69.5%(41/59)、65.6%(21/32)、48%(12/25)和56.5%(13/23);血清抗-HEV IgG阳性检出率分别为90.2%(46/51)、88.1%(52/59)、96.9%(31/32)、100%(25/25)和100.0%(23/23)。结论 AHE患者血清抗-HEV IgM、IgG和HEV RNA存在一定的变化规律,血清抗-HEV IgG阳性,结合典型的急性肝炎过程和排除其他病因后,可以诊断为AHE。     

Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E virus

Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern China. However, the evaluation of antibodies to HEV during consecutive time periods after infection has not been reported. We utilized enzyme immunosorbent assay (ELISA) to detect IgM and IgG anti-HEV in consecutive serum specimens from patients with acute hepatitis E and compared that data with detection rates of IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be detected as early as 4 days after onset of disease symptoms in some patients. The detection rate of IgM anti-HEV is significantly higher in specimens collected within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks after onset (67.6%) (P<0.005). IgM anti-HEV had a similar pattern to IgM anti-HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti-HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P<0.005). One should be cautioned against making a diagnosis of HEV infection solely by the currently available assays for IgG anti-HEV. In conclusion, IgM anti-HEV can be used as a reliable and sensitive marker for recent HEV infection, but serum specimens should be collected within 4 weeks after onset of symptoms to avoid false-negative results. In contrast, we should be aware of the failure to develop IgG anti-HEV in some patients. These patients carry the risk of reinfection.     

Seroepidemiology and genetic characterization of hepatitis E virus in western Yunnan Province

Objective:To investigate the seroepidemiology and genetic characterization of hepatitis E virus(HEV) in western Yunnan Province.Methods:Questionnaire survey was conducted among1638 residents in western Yunnan Province using stratified sampling method.Enzyme-linked immunosorbent assay was used to detect serum anti-HEV IgG and IgM.HEV RNA was extracted from patients with serum anti-HEV IgM positive.The open reading flame 2(ORF2) of HEV that was amplified by nested RT-PCR was sequenced and compared with standard HEV genotypes 1-4.Results:Serum anti-HEV positive was found in 13.929(228/1638) residents.The HEV infection rate in males was significantly higher than that in females with a ratio of 1.47(P0.01).20-30 and30-40 years old young men showed the highest incidence.20.57%and 20.78%.respectively.While10-20 and 20-30 years old young women exhibited the highest infection rate,11.85%and 15.60%,respectively.According to occupation,the highest HEV infection rate was observed in farmers(20.35%) and migrants(16.50%).We isolated 10 individual HEV isolates from 31 patients with serum anti-HEV IgM positive.Homology analysis and phylogenetic analysis indicated that these10 HEV isolates belonged to HEV genotype 4 with the homology of 78.65%-94.71%.Conclusions:The HEV infection rate is high in western Yunnan Province.HEV genotype 4 is the leading cause of HEV infection and young farmers and migrants are the main infected population.     

Hepatitis E virus infection after haploidentical haematopoietic stem cell transplantation: incidence and clinical course

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6–55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0–5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.     

Establishment of competitive binding assay to detect and differentiate hepatitis E virus infection

Introduction and ObjectivesThis study was undertaken to demonstrate a promising approach for detection and differentiation the serum immunoglobulin G (IgG) against hepatitis E virus (anti-HEV IgG) using a competitive binding assay established with known genotype-specific monoclonal antibodies (mAbs) 2B1 and 4C5.Materials and methodsThe mAb 2B1 derived from genotype 1 hepatitis E virus (HEV) antigen and specifically reacted with genotype 1, 2 antigens; 4C5 induced by genotype 4 HEV antigen was specific to genotypes 3, 4 antigens. The 2B1 and 4C5 were labeled with Horseradish peroxidase (HRP), respectively. Subsequently, the titers of coated antigens and HRP-conjugated mAbs for establishment of competitive binding assay were determined by enzyme linked immunosorbent assay (ELISA). And then, the competitive binding assay was performed to assess the inhibition percentage of mAbs binding to antigens inhibited by different genotypes anti-HEV IgG.ResultsThe results of competitive binding assay revealed that genotype 1 anti-HEV IgG could inhibit the binding of mAb 2B1 to genotype 1 antigen more strongly than that of mAb 4C5 to genotype 4 antigen. Whereas, the genotype 3 or 4 anti-HEV IgG could inhibit the binding of mAb 4C5 to genotype 4 antigen more remarkably than that of mAb 2B1 to genotype 1 antigen.ConclusionsThese findings provided us a valuable approach for detection and differentiation the HEV infection derived from genotypes 1, 2 (human) or genotypes 3, 4 (zoonosis).     

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

Background. Acute hepatitis E virus (HEV) infection in solid organ transplant recipients is rare, but can cause severe hepatic and extrahepatic complications. We sought to identify the pretransplant prevalence of HEV infection in heart and kidney candidates and any associated risk factors for infection.Material and methods. Stored frozen serum from patients undergoing evaluation for transplant was tested for HEV immunoglobulin G (IgG) antibodies and HEV RNA. All patients were seen at Mayo Clinic Hospital, Phoenix, Arizona, with 333 patients evaluated for heart (n = 132) or kidney (n = 201) transplant. HEV IgG antibodies (anti-HEV IgG) were measured by enzyme-linked immunosorbent assay, and HEV RNA by a noncommercial nucleic acid amplification assay.Results. The prevalence of anti-HEV IgG was 11.4% (15/132) for heart transplant candidates and 8.5% (17/201) for kidney transplant candidates, with an overall seroprevalence of 9.6% (32/333). None of the patients tested positive for HEV RNA in the serum. On multivariable analysis, age older than 60 years was associated with HEV infection (adjusted odds ratio, 3.34; 95% CI, 1.54-7.24; P = 0.002).Conclusions. We conclude that there was no evidence of acute HEV infection in this pretransplant population and that older age seems to be associated with positive anti-HEV IgG.     

The Prevalence of Hepatitis E Virus Infection in the Adult Turkish Population: A Systematic Review of the Literature and Prevalence Study in Blood Donors in Mersin Province

BackgroundThe hepatitis E virus (HEV) is an RNA virus that causes acute hepatitis, and can become chronic in immunocompromised patients, though this is rare. The frequency of HEV infection varies, depending on factors such as geographical region, socioeconomic level, and age. Despite limited studies on the adult population in Turkey, there is no current information about HEV frequency in our country. Therefore, we aimed to scrutinize the data found from such studies, in comparison to our own results. MethodsA total of 900 volunteers who applied to donate blood to the University Hospital Blood Center and accepted the use of their data were enrolled in the study. Serum anti-HEV IgG antibody (Ab) was examined by the enzyme-linked immunosorbent assays method. The donors’ location, occupation, and animal contact status were determined. In addition, we evaluated the full text and conference papers (in Turkish or English) of Turkey-based HEV seroprevalence studies from 1990-2020, investigating the adult population.ResultsThe average age of the 900 volunteers in the study was 35.22 ± 9.60 years, of whom 889 (98.7%) were men. Anti-HEV IgG was positive in 12.8% of the serum samples. The average age of the volunteers who were seropositive was 40.40 ± 9.72 years, and 98.2% were men. No association was found between anti-HEV IgG positivity and occupation, place of residence, and contact with animals. An evaluation of the studies conducted in Turkey reveals that the average HEV infection seroprevalence is 9.52% in the healthy population, and the prevalence is increased in the region of Southeastern Anatolia. Patients with acute hepatitis and hemodialysis also had increased rates. ConclusionThe anti-HEV IgG seropositivity rate in healthy blood donors in Mersin province was 12.8%, and was similar to the rates reported earlier in our country. However, this rate, found in a sample of individuals from a healthy society, causes concern about what the frequency may be in sick people. Wide-ranging community screening is needed.     

Hepatitis Agents with Enteric Transmission – An Epidemiological Analysis

Background: Viral hepatitis is characterized by special clinical, biochemical and serological findings. This study was planned to determine the seroprevalence, epidemiological characteristics and clinical and biochemical findings of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections during an outbreak of jaundice. Materials and Methods: 340 children aged 5–16 years were included. Clinical findings and alanine aminotransferase (ALT) levels were documented. Anti-HAV IgG and IgM in addition to anti-HEV IgG and IgM were determined by microELISA. Results: Clinical findings, high levels of ALT, anti-HAV IgM and IgG, anti-HEV IgM and IgG were present in 6%, 23%, 17%, 100%, 7% and 9% of cases, respectively. The relationship between ALT levels and anti-HAV or anti-HEV IgM seropositivity was significant (p ≤ 0.0001). Conclusion: HAV and HEV infection were both caused by a contaminated water supply. Received: September 21, 2001 · Revision accepted: April 23, 2002 RID="*" ID="*"This study was presented as a poster at 11th European Congress of Clinical Microbiology and Infectious Diseases, Istanbul, Turkey, April 1–4, 2001. A. R. ?rmeci (corresponding author)