Increased risk of hepatitis E virus infection in schizophrenia

Until now, the risk of HEV infection in schizophrenia was unknown. The present results showed that the seroprevalence of anti-HEV IgG and anti-HEV IgM in schizophrenia were significantly higher than that in healthy controls. Anti-HEV IgG positivity increased with age and with the duration of disease in schizophrenia patients. Moreover, schizophrenia patients with increased CD4⁺/CD8⁺ T-cell ratios (>2.03) had higher anti-HEV IgG detection rates than those with normal ratios (1.05-2.03). Compared with the schizophrenia patients who tested anti-HEV IgG negative, the levels of interleukin-4 and interleukin-10 (Th2 cytokines) were significantly higher, while the interleukin-12 (Th1 cytokine) level was significantly lower, in those with anti-HEV IgG positivity. Of five schizophrenia patients who were anti-HEV IgM positive, four had elevated CD4⁺/CD8⁺ T-cell ratios. HEV RNA was isolated from one of these four patients and classified as genotype 4. Anti-HEV IgM positivity was not detected among healthy controls. Therefore, schizophrenia patients exhibited a higher risk of HEV infection than controls.     

Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised

BackgroundRecently, cases of chronic hepatitis E have been identified in immunocompromised patients.ObjectivesTo evaluate the prevalence of anti-HEV IgG antibodies and the persistence of HEV-RNA in sera of immunocompromised patients with regular follow-up at Saint-Louis Hospital in Paris, France.Study design307 samples collected from 261 HIV-infected patients and 46 kidney transplant (KT)-patients were retrospectively tested for the presence of the following hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index, and HEV-RNA.ResultsAnti-HEV IgG positive serology was found in 4 HIV-infected patients (1.5%) and 3 KT-patients (6.5%), leading to an overall seroprevalence of 2.3%. HEV-RNA detection was not observed among 55 HIV-patients at higher risk of chronic HEV (<200 CD4 cells/mm³, elevated alanine aminotransferase (ALT) levels, and/or positive anti-HEV antibodies) and among 44 KT-patients. None of the seven patients had anti-HEV IgM antibodies, thereby excluding any acute infection. The IgG avidity index confirmed past HEV infection among tested patients.ConclusionsThe low seroprevalence observed in the Paris region does not warrant a systematic evaluation of HEV infection in immunocompromised patients. However, HEV infection must be examined as a possibility if unexplained increases in ALT should occur and after more common viral hepatitis infections are excluded.     

无偿献血人群戊型肝炎病毒感染情况调查

目的调查绍兴市街头无偿献血者戊型肝炎病毒感染情况。方法3701例无偿献血者标本采用ELISA方法检测抗-HEV IgG和抗-HEV IgM,RT-PCR检测抗-HEV IgM阳性血清HEV RNA。结果本市无偿献血者抗-HEV IgG阳性率为29.91%(1107/3701);抗-HEVIgM阳性率为1.35%(50/3701);HEV RNA阳性6例,检出率为0.16%(6/3701),均为HEV基因1型;各季节抗-HEV IgG和抗-HEV IgM的阳性检出率无显著差异。结论加强对献血者感染HEV情况的检测和研究,对保证用血安全,完善安全输血的保障体系有切实的意义。     

Incidence and seroprevalence of hepatitis E virus infection in pregnant women infected with hepatitis B virus and antibody placental transfer in infants

BackgroundHepatitis E has poor outcomes in pregnant women. Superinfection of hepatitis E virus (HEV) in patients infected with hepatitis B virus (HBV) may worsen liver disease.ObjectivesTo estimate the incidence and seroprevalence of HEV infection among HBV-infected pregnant women, to investigate the transplacental transfer of maternal anti-HEV IgG, and to compare the maternal and neonatal outcomes in anti-HEV positive and negative pregnant women.Study designTotally 391 HBV-infected pregnant women were recruited from April 2012 to October 2014. Paired mothers and infants were followed up at an average 9.8 months postpartum. Anti-HEV IgG and IgM were tested by ELISA.ResultsOf the pregnant women, none was anti-HEV IgM positive and 42 (10.7%) were IgG positive. At the follow-up, 3 seronegative women converted to anti-HEV IgG positive, with an estimated incidence of 17 per 1000 person-years. No significant differences of gestational age, preterm birth rate, Apgar score and birthweight were observed between newborns of anti-HEV IgG positive and negative mothers. Of the 42 neonates born to anti-HEV IgG positive mothers, 38 (90.5%) had anti-HEV IgG in their cord blood. The neonatal and maternal anti-HEV IgG levels were positively correlated (r = 0.827, p < 0.05). All infants were negative for both anti-HEV IgM and IgG at the follow-up.ConclusionsHBV-infected pregnant women rarely have novel HEV infection during late pregnancy in Jiangsu, China. Maternal anti-HEV IgG efficiently transfers into the fetuses, and disappears in infants before 10 months old.     

Hepatitis E virus infection in the HIV-positive patient

Hepatitis E virus (HEV) is a RNA virus that can cause hepatitis. In immunocompetent individuals, infection with HEV usually leads to asymptomatic seroconversion. However, in immunosuppressed patients, such as transplant recipients, HEV can develop into a chronic infection. Studies regarding the seroprevalence and clinical implications of HEV in patients infected with the human immunodeficiency virus (HIV) are conflicting. Levels of CD4 count in blood seem to be the most widely associated risk factor, while other factors such as meat consumption or proximity to animals are less clearly associated with HEV infection. Progression to chronicity, as well as extrahepatic manifestations of HEV seem rare in HIV, and the implications of HEV in liver disease progression are poorly understood in the HIV-infected. In this review we describe the epidemiology, risk factors, and clinical implications of HEV infection in individuals infected with HIV.     

Hepatitis E virus seroprevalence in acute viral hepatitis in a developed country confirmed by a supplemental assay

Hepatitis E virus (HEV) infection is prevalent among cases of acute viral hepatitis in young adults in developing countries. HEV infection is not restricted to endemic areas, but would appear to be worldwide in distribution. In order to document the incidence of HEV infection in acute hepatitis cases in a developed country, IgG and IgM anti-HEV antibodies and HEV RNA were tested in 101 Caucasian patients with acute viral hepatitis; 92 of these cases had markers of acute viral hepatitis other than HEV. Forty-seven (46.5%) cases had IgG anti-HEV; IgM anti-HEV and HEV viremia were not detected. As the incidence of anti-HEV was higher than would be expected, the possibility of the occurrence of false positive results was subsequently investigated. Supplemental antibody testing, using a broadly reactive epitope region, reduced the frequency of anti-HEV to 17%. Therefore, supplemental antibody testing confirms the hepatitis E virus seroprevalence in a developed country. Since IgM anti-HEV and HEV viremia were not detected, persons with IgG anti-HEV may be “subclinical HEV cases,” or have long-lived antibodies in their circulation. © 1996 Wiley-Liss, Inc.     

Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E

Infection with hepatitis E virus (HEV) may be diagnosed by the presence of HEV RNA or anti-HEV antibodies. An enzyme immunoassay (EIA) was developed for the detection of antigen. Twenty-four monoclonal antibodies (mAbs) were produced. An indirect sandwich EIA was developed to detect HEV antigen using a combination of three mAbs as coating antibodies. Approximately 44.6% (33/74), 28.6% (50/175), and none (0/27) of sera positive for anti-HEV IgM alone, both anti-HEV IgM and IgG, and anti-HEV IgG alone also were positive for HEV antigen using this EIA. Forty-two HEV antibody-positive sera were tested for HEV RNA and antigen in parallel and the concordance was 81.0% (34/42). All PCR products were found to belong to HEV genotype 4. In order to evaluate the temporal relationship between HEV antigen positivity and HEV RNA, anti-HEV IgG and IgM, and ALT concentrations, macaques were infected with HEV genotypes 1 and 4 and serial samples were collected. The results showed that the antigen EIA can detect the capsid proteins of both genotypes. HEV antigen was detectable prior to ALT elevation and the appearance of anti-HEV antibodies in the infected monkeys and lasted for several weeks in all cases. HEV antigen became detectable in the serum at almost the same time as HEV RNA in feces but persisted for 4 weeks less than HEV RNA. This assay should be valuable for the diagnosis of acute hepatitis E, particularly in the window period prior to seroconversion to anti-HEV.     

Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan

Ongoing subclinical infection of hepatitis E virus (HEV) has not been fully studied. In the present study, serum samples were collected from 6700 voluntary blood donors with an elevated alanine aminotransferase (ALT) level of 61-476 IU/l at a Japanese Red Cross Blood Center, and were tested for the presence of IgG, IgM and IgA classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA by nested RT-PCR. Overall, 479 blood donors (7.1%) were positive for anti-HEV IgG, including 8 donors with anti-HEV IgM and 7 donors with anti-HEV IgA. Among the nine donors with anti-HEV IgM and/or anti-HEV IgA, six had detectable HEV RNA. The presence of HEV RNA was further tested in 10-sample minipools of sera from the remaining 6691 donors, and three donors including one without anti-HEV IgG were found to be positive for HEV RNA. When stratified by ALT level, the prevalence of HEV RNA was significantly higher among the 109 donors with ALT > or = 201 IU/l than among the 6591 donors with ALT of 61-200 IU/l (2.8% vs. 0.1%, P < 0.0001). The HEV isolates obtained from the nine viremic donors segregated into genotype 3, shared a wide range of identities of 85.6-98.5% and were 87.3-93.9% similar to the Japan-indigenous HEV strain (JRA1), in the 412-nucleotide sequence of open reading frame 2. This study suggests that approximately 3% of Japanese individuals with ALT > or = 201 IU/l have ongoing subclinical infection with various HEV strains.     

Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion

To investigate the prevalence of hepatitis E virus (HEV) infection among patients on maintenance hemodialysis, serum samples collected in January 2003 from 416 patients who had been undergoing hemodialysis for 7.6 +/- 6.3 (mean +/- standard deviation) (range, 0.3-26.0) years in a dialysis unit in Japan and serum samples that had been collected from these patients at the start of hemodialysis were tested for IgG antibodies to HEV (anti-HEV IgG) by an "in-house" enzyme-linked immunosorbent assay (ELISA). Overall, 39 patients (9.4%) had anti-HEV IgG in January 2003, and included 35 patients (8.4%) who had already been positive for anti-HEV IgG at the start of hemodialysis and 4 patients (1%) who seroconverted after initiation of hemodialysis. Periodic serum samples that had been collected from the four seroconverted patients were tested for HEV antibodies and HEV RNA. The four patients became positive for anti-HEV IgG in 1979, 1980, 1988, or 2003, and continued to be seropositive until the end of the observation period. Although anti-HEV IgM was not detectable in the four patients, three were infected transiently with apparently Japanese indigenous HEV strains of genotype 3. The patient who contracted HEV infection in 1979 had been transfused with 2 U of blood 21 days before the transient viremia: one of the two stored pilot serum samples had detectable HEV RNA with 100% identity to that recovered from the patient. Our study provides evidence of transfusion-transmitted HEV infection in Japan in 1979, and that the prevalence of de novo HEV infection during hemodialysis was low (1.1% or 4/374).     

Antibodies to hepatitis E virus among chinese patients with acute hepatitis in Taiwan

The prevalence of antibodies to hepatitis E virus (anti-HEV) was investigated in patients with acute hepatitis, and correlated with the clinical features. Sera from 110 patients with acute hepatitis and 60 healthy controls were tested for anti-HEV, antibody to hepatitis C virus (anti-HCV), and hepatitis B surface antigen (HBsAg). There were significant differences in the prevalence of anti-HEV, anti-HCV, and HBsAg between patients and controls (21.8% vs. 0%, 16.3% vs. 1.6% and 58.1% vs. 18.0%, respectively). Anti-HEV was detected in 6 (25.0%) of 24 patients with anti-HCV, 6 (9.3%) of 64 patients with HBsAg, and another 6 (22.2%) of 27 patients with acute hepatitis non-A, non-B, non-C. Anti-HEV was found in 15 men and three women, whose ages ranged from 34 to 75 (median, 57) years old. The median age of patients with anti-HEV was older than that in patients without this antibody (57 vs. 38 years; P = 0.001). The prevalence of anti-HEV in patients with anti-HCV alone (35.2%) was higher than that (11.1%) in patients with HBsAg alone (P = 0.03). Compared to patients without anti-HEV, HEV-infected patients had a higher frequency of travel to a foreign country (P = 0.0001), had a lower HBsAg rate (P = 0.019), and had higher serum alkaline phosphatase levels (P = 0.04) and gamma-glutamyl transpeptidase levels (P = 0.01). In conclusion, HEV infection occurs in 22.2% of patients with acute hepatitis non-A, non-B, non-C. HEV superinfection may occur in patients with chronic hepatitis B or C virus infection. © 1994 Wiley-Liss, Inc.     

Seroepidemiology of hepatitis E virus in patients with non-A, non-B, non-C hepatitis in Hungary

Many cases of acute hepatitis remain undiagnosed and the hepatitis E virus (HEV) is emerging in industrialized countries. The aim of this study was to assess the role HEV as causative agent in acute non-A, non-B, and non-C hepatitis patients in Hungary. 10.5% of the 264 acute non-A, non-B, and non-C hepatitis patients tested had anti-HEV IgG and 1.9% had anti-HEV IgM as tested by ELISA. After confirmation by Western blot 6.1% of the acute non-A, non-B, and non-C hepatitis patients had anti-HEV IgG antibodies only and 1.1% of the patients had both IgG and IgM. All 19 patients that were positive for anti-HEV IgG and/or IgM tested negative for HEV RNA by PCR. Only a small proportion of the acute hepatitis cases in the southwest of Hungary are assumed to be attributed to HEV infection, however, hepatitis E should be considered along with hepatitis A, B, and C in the diagnosis of acute hepatitis.     

Case report: Role of hepatitis E virus in the etiology of community-acquired non-A,non-B hepatitis in greece

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc.     

Exposure to hepatitis E virus in hemodialysis patients from west-central Poland

Hepatitis E virus (HEV) causes travel-related but also locally acquired infections in industrialized parts of the world, including European countries. Food and blood transfusions are possible sources of transmission. Infections caused by zoonotic variants of the virus (particularly HEV-3) may progress to chronic liver disease in a nonnegligible proportion of immunocompromised people. The aim of this study was to assess the prevalence of serological markers of HEV infection in 189 patients on renal replacement therapy (RRT, currently on hemodialysis, HD) living in west-central Poland and to determine the factors related to HEV exposure in this group. Testing was carried out using commonly used commercial assays (Wantai Biological Pharmacy Enterprise Co, Beijing, China). Anti-HEV IgG was detected in 94 patients (49.7%); none of the participants had anti-HEV IgM or HEV Ag. Patients on RRT (HD) for less than 6 months were significantly more likely to be anti-HEV IgG-positive than dependent of RRT (HD) for more than half a year (80% vs 47%; P = .014). Exposure to HEV in patients from west-central Poland is frequent, but no clear sources of this infection have been identified. There were no serological features of ongoing liver disease caused by HEV in the study subjects.     

Cross-protection of hepatitis E virus genotypes 1 and 4 in rhesus macaques

The purpose of this study was to determine cross-protection between HEV genotypes 1 and 4, which are prevalent in China. Fecal suspensions of genotypes 1 and 4 from patients, as well as genotype 4 from swine, were inoculated intravenously into rhesus macaques. Each inoculum contained 5 x 10(4) genome equivalents of HEV. After infection, serum and fecal samples were collected serially and the levels of alanine aminotransferase (ALT) and anti-HEV IgG and IgM in sera, and HEV RNA in fecal samples, were measured. Liver biopsies were carried out. All the infected monkeys (12/12) developed anti-HEV IgG and exhibited fecal shedding of virus. IgM was detected in 11 of 12, and ALT elevation occurred about 2-6 weeks post-inoculation in 10 of 12, infected monkeys. Hepatic histopathology was consistent with acute viral hepatitis and the ORF2 antigen of HEV was detected in the granular cytoplasm of hepatocytes by immunohistochemistry. After recovery from their initial HEV infection, the monkeys were challenged with a heterologous genotype or heterologous source of HEV and monitored for hepatitis and fecal shedding. Previous infection with HEV completely or partially protected against subsequent challenge with a heterologous virus, because 7 of 11 monkeys did not develop HEV infection or shed virus in the feces, and none of them developed hepatitis or exhibited ALT elevation or liver biopsy findings of hepatitis. In conclusion, previous HEV infection may give rise to cross-genotype and cross-host-species protection.     

Molecular characteristic-based epidemiology of hepatitis B, C, and E viruses and GB virus C/hepatitis G virus in Myanmar

We carried out a molecular characteristic-based epidemiological survey of various hepatitis viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and GB virus C (GBV-C)/hepatitis G virus (HGV), in Myanmar. The study population of 403 subjects consisted of 213 healthy individuals residing in the city of Yangon, Myanmar, and the surrounding suburbs and 190 liver disease patients (155 virus-related liver disease patients and 35 nonviral disease patients). The infection rates of the viruses among the 213 healthy subjects were as follows: 8% for HBV (16 patients), 2% for HCV (4 patients), and 8% for GBV-C/HGV (17 patients). In contrast, for 155 patients with acute hepatitis, chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma, the infection rates were 30% for HBV (46 patients), 27% for HCV (41 patients), and 11% for GBV-C/HGV (17 patients). In the nonviral liver disease group of 35 patients with alcoholic liver disease, fatty liver, liver abscess, and biliary disease, the infection rates were 6% for HBV (2 patients), 20% for HCV (7 patients), and 26% for GBV-C/HGV (9 patients). The most common viral genotypes were type C of HBV (77%), type 3b of HCV (67%), and type 2 of GBV-C/HGV (67%). Moreover, testing for HEV among 371 subjects resulted in the detection of anti-HEV immunoglobulin G (IgG) in 117 patients (32%). The age prevalence of anti-HEV IgG was 3% for patients younger than 20 years and 30% or more for patients 20 years of age or older. Furthermore, a high prevalence of anti-HEV IgG (24%) was also found in swine living together with humans in Yangon. These results suggest that these hepatitis virus infections are widespread in Myanmar and have led to a high incidence of acute and chronic liver disease patients in the region.     

Serological studies of an enterically transmitted non-A,non-B hepatitis in Somalia

An outbreak of an acute sporadic viral hepatitis occurring at three villages in the lower Shebli region of southern Somalia was studied. Sera were examined for antibodies to hepatitis E virus (HEV) antigen by a recently developed enzymelinked immunosorbent assay. The prevalence of anti-HEV ranged from 77.8% to 94.0% among the three villages. Anti-HEV prevalence did not differ significantly with age or sex. HEV infections were widely distributed among all age groups, without a preponderance in any specific age category. Overall, 97.6% of afflicted patients who were examined 6–10 days after onset of jaundice developed either IgM or IgG anti-HEV. © 1993 Wiley-Liss, Inc.     

IgM and IgG antibodies to hepatitis E virus (HEV) detected by an enzyme immunoassay based on an HEV-specific artificial recombinant mosaic protein

To develop an enzyme immunoassay (EIA) for IgM antibody to hepatitis E virus (HEV) (IgM anti-HEV) and IgG antibody to HEV (IgG anti-HEV), a synthetic gene encoding several liner immuno-dominant antigenic epitopes from HEV structural proteins was assembled as a chimeric recombinant mosaic protein (Mpr) with glutathione S-transferase and used as an immunodiagnostic target. In addition, a neutralization confirmation test was developed using individual synthetic peptides. Among 614 patients with acute hepatitis from 10 geographically distinct outbreaks, IgG anti-HEV was found in 546 (88.9%), with a range of 77–100% depending on the outbreak. Of 130 patients tested for IgM anti-HEV, 126 (96.9%) were positive. Among patients tested within 4 months of onset of jaundice, 37/37 (100%) were IgG anti-HEV positive. For patients from whom sera were collected 1–16 days after onset of jaundice, the geometric mean IgG titer (GMT) was 1:47,000; the GMT increased to 1:70,710 30–40 days after onset of jaundice and decreased to 1:1,778 3–4 months after the onset of jaundice. For patients tested 6–8 months after onset of jaundice, 11/12 (92%) were IgG anti-HEV positive, and the GMT was 1:2,908. IgM anti-HEV was detected in 43/43 (100%) sera collected 1–40 days after onset of jaundice, and the GMT for IgM anti-HEV was 1:10,000 at that time. For sera collected 3–4 and 6–12 months after onset of jaundice, 7/14 (50%) and 5/12 (40%) respectively, were IgM anti-HEV positive. In conclusion, an artificial mosaic protein composed of linear antigenic epitopes from open reading frame 2 (ORF2) and ORF3 of HEV has been successfully applied to the development of a sensitive and specific EIA for the detection of IgG and IgM anti-HEV activity. These assays were used for the verification of HEV infection in outbreak settings and for the diagnosis of HEV infection in sporadic cases. © 1996 Wiley-Liss, Inc.     

Prevalence of antibodies to hepatitis E virus in residents of a district in Havana, Cuba

A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in a district of Havana, where hepatitis A virus (HAV) is considered endemic. The levels of anti-HEV antibodies were evaluated by enzyme-linked immunosorbent assay (ELISA) based on the recombinant protein GST-ORF2.1. Anti-HEV antibodies were detected in 11 of 209 (5.3%) of serum samples, compared to 71.3% for anti-HAV antibodies. No risk factors reported previously for HEV infection showed a significant association with the presence of anti-HEV antibodies, whereas anti-HAV antibodies were strongly associated with increasing age. HEV may be considered endemic in this area and is likely to have a significant clinical impact.     

Comparison of hepatitis A and E virus infections among healthy children in Mongolia: evidence for infection with a subgenotype IA HAV in children

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was investigated serologically and molecularly among 717 apparently healthy individuals of 0-20 years of age (mean +/- standard deviation, 8.6 +/- 4.9 years) using serum samples obtained between October 2005 and January 2006. Total antibody against HAV (anti-HAV [total]) was detected in 494 (68.9%) of the 717 subjects, while IgG antibody against HEV (anti-HEV IgG) was detected in only five subjects (0.7%) (P < 0.0001). All five subjects who had anti-HEV IgG, were negative for anti-HEV IgM and HEV RNA. Anti-HAV was detectable in 24 (75.0%) of the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to <12 months. The prevalence of anti-HAV was 19.5% (17/87) in the age group of 1-3 years, and it increased to 50.0% (69/138) in the age group of 4-6 years, and further to 81.4% (105/129) in the age group of 7-9 years. Of note, 97.2% of the subjects in the age group of 16-20 years had anti-HAV. The presence of HAV RNA was tested in all 717 subjects, and three children of 1, 4, or 8 years of age were found to have detectable HAV RNA (subgenotype IA). No subject had a history of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV infection lacking overt clinical features was prevalent among children in Mongolia.     

Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) Is highly specific for diagnosis of acute HEV infection

Serum samples collected from 68 patients (age, mean +/- the standard deviation [SD], 56.3 +/- 12.8 years) at admission who were subsequently molecularly diagnosed as having hepatitis E and from 2,781 individuals who were assumed not to have been recently infected with hepatitis E virus (HEV; negative controls; 52.9 +/- 18.9 years), were tested for immunoglobulin M (IgM) and IgA classes of antibodies to HEV (anti-HEV) by in-house solid-phase enzyme immunoassay with recombinant open reading frame 2 protein expressed in the pupae of silkworm as the antigen probe. The 68 patients with hepatitis E had both anti-HEV IgM and anti-HEV IgA. Among the 2,781 controls, 16 (0.6%) had anti-HEV IgM alone and 4 (0.1%) had anti-HEV IgA alone: these IgA/IgM anti-HEV-positive individuals were not only negative for HEV RNA but lack IgG anti-HEV antibody as well (at least in most of the cases). Periodic serum samples obtained from 15 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, and anti-HEV IgA. Although HEV RNA was detectable in the serum until 7 to 40 (21.4 +/- 9.7) days after disease onset, both IgM and IgA anti-HEV antibodies were detectable until 37, 55, or 62 days after disease onset in three patients and up through the end of the observation period (50 to 144 days) in 12 patients. These results indicate that detection of anti-HEV IgA alone or along with anti-HEV IgM is useful for serological diagnosis of hepatitis E with increased specificity and longer duration of positivity than that by RNA detection.