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.     

Serological and molecular studies on subclinical hepatitis E virus infection using periodic serum samples obtained from healthy individuals

Subclinical hepatitis E virus (HEV) infection among healthy individuals was studied serologically and molecularly. Serum samples collected at screening between March and April 2004 (or just before retirement) from 266 medical staff members (35 males, 231 females) who had been working for 8.8 +/- 8.5 (mean +/- standard deviation, range, 0.3-35.1) years in a city hospital in Japan and serum samples that had been collected from these staff members at the start of employment were tested for IgA, IgM, and IgG antibodies to HEV (anti-HEV) by in-house enzyme-linked immunosorbent assays. Overall, six subjects (2.3%) tested positive for anti-HEV IgG at the screening; among them, four subjects (1.5%) had already been positive for anti-HEV IgG at the start of employment and two subjects (0.8%) seroconverted after initiation of employment. Periodic serum samples that had been collected from the two seroconverted subjects were tested for HEV antibodies and HEV RNA. The two subjects became positive for anti-HEV IgG in 1978 or 2003, respectively, with no discernible elevation in alanine aminotransferase (ALT) level, and continued to be seropositive up through the screening date. Although anti-HEV IgM was not detectable in the two subjects, one was infected transiently with Japan-indigenous HEV strain of genotype 3 and the other was positive transiently for anti-HEV IgA. The present study indicates that even an individual with subclinical HEV infection had evidence of transient viremia in the absence of ALT elevation and that anti-HEV IgA detection may be useful for serological diagnosis of recent subclinical HEV infection.     

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).     

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.     

Prevalence of hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: A hospital based study

Context: Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. Aim: The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Settings and Design: Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Subjects and Methods: Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Statistical Analysis Used: Fisher’s exact test was used and a P < 0.05 was considered to be statistically significant. Results: Of the 267 viral hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. Conclusions: To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.     

检测病毒性肝炎患者血清中SEN病毒及其临床意义

目的：检测病毒性肝炎患者血清中SEN病毒D和H(SENV-D、SENV-H),并探讨其临床意义。方法：采用巢式聚合酶链反应法（nPCR）检测甲、乙、丙、戊型肝炎和非甲－戊型肝炎患者血清中SENV-D和SENV-H DNA。结果：在180例病毒性肝炎患者血清中，SENV-D和SENV-H检出率分别为17.2%(31/180)和5.6%(10/180)，总检出率为18.3%(33/180)、甲、乙、丙、戊型肝炎患者的SENV-D/H检出率高于非甲－戊型肝炎患者。从甲、乙、丙、戊型肝炎和非甲－戊型肝炎患者分离的SENV-D/H核苷酸序列，与SENV-D/H原型株比较，其同源性在94％以上。甲、乙、丙和戊型肝炎患者有无SENV-D/H合并感染，其血清生化学指标无明显差异。结论：SENV-D/H可能不是非甲-戊型肝炎的病原，甲、乙、丙和戊型肝炎患者合并感染SENV-D/H并不加重病情。     

Acute viral hepatitis types E,A, and B singly and in combination in acute liver failure in children in North India

The aetiological agents responsible for, and the outcome of, acute liver failure were investigated prospectively in 44 children (29 males, 15 females) attending a tertiary health care facility in India. The children were between the ages of 2 months and 13 years. Studies for viral infections and other etiologies could be carried out in 40 patients. Specific aetiological labels were possible in 35 (87.5%) patients. Thirty (75%) had evidence of acute viral hepatitis. Acute hepatitis E virus (HEV) infection was found in a total of 18 children, with hepatitis A (HAV) in 16, hepatitis B in 5, and C in 1. Seven had isolated infection with hepatitis E, five with A, and four with B. Nine had both E and A infection. Superinfection of HEV was observed in a child with Indian childhood cirrhosis (ICC). Acute HEV infection was confirmed by immunoblot assay in all the patients and in eight of these, HEV-RNA was also detected in the serum. HAV was involved in 37.5% of cases with isolated infection in 10% (4 of 40). The aetiological factors associated with acute liver failure, apart from HAV and HEV, were other hepatotropic viruses (22.5%), Wilson's disease (5%), ICC (5%), and hepatotoxic drugs (7.5%). In five patients, no serological evidence of acute viral hepatitis could be found, neither did the metabolic screen yield any result. It was observed that enterically transmitted hepatitis viruses (HAV and HEV) were associated with 60% of acute hepatic failure in children. Mixed infection of HAV and HEV formed the single largest aetiological subgroup. In developing countries, where hepatitis A and E infections are endemic, severe complications can arise in the case of mixed infection. This may contribute to most of the mortality from acute liver failure during childhood. © 1996 Wiley-Liss, Inc.     

Epidemiological and virological characteristics of symptomatic acute hepatitis E in Greater Cairo,Egypt

The aim of the study was to describe the characteristics of acute hepatitis E in Greater Cairo. Patients with acute hepatitis E were identified through a surveillance of acute hepatitis using the following definition: recent (<3 weeks) onset of fever or jaundice, alanine aminotransferase at least three times the upper limit of normal (uln), negative markers for other causes of viral hepatitis and detectable hepatitis E virus (HEV) RNA. Comparison of the liver tests between acute hepatitis E and hepatitis A virus (HAV), case–control analysis (four sex-matched and age-matched (±1 year) HAV controls per case) to explore risk factors and phylogenetic analyses were performed. Of the 17 acute HEV patients identified between 2002 and 2007, 14 were male. Median age was 16 years (interquartile range 13-22). Compared with HAV (n = 68 sex-matched and ±1 year age-matched), HEV patients had higher bilirubin (mean (SD) 10.9 (5.7) uln versus 7.5 (4.4) uln, p 0.05) and aspartate aminotransferase levels (38.6 (27.1) uln versus 18.3 (18.1) uln, p 0.02). Co-infection (hepatitis C virus RNA or hepatitis B surface (HBs) -antigen positive/IgM anti-hepatitis B core (HBc) anitgen negative) was diagnosed in four patients. In univariate matched analysis (17 cases, 68 matched controls), HEV cases were more likely to live in a rural area than HAV controls (matched OR 7.9; 95% CI 2.0-30.4). Of the 16 isolates confirmed as genotype 1, 15 belonged to the same cluster with 94-98.5% identity in the open-reading frame 2 region. Our findings documented the sporadic nature of HEV in Greater Cairo, characterized a large number of Egyptian HEV genotype 1 strains and identified living in a rural area as a potential risk factor for infection.     

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.     

Incidence of hepatitis A virus (HAV) infection in rural Liberia

To provide background for future hepatitis A vaccine trials, sera were collected from 0- to 4-year-old Liberian infants and their mothers on two occasions an average of 14.75 months apart and tested for antibody to hepatitis A virus (anti-HAV). The prevalence of anti-HAV rose from 2.5% in infants 0-6 months of age to 70% in children 3-4 years of age and did not differ between male and female infants. The annual incidence of new infections was slightly lower in the first year of life (35%) than in the subsequent 3 years, when it averaged 45%. The presence of HBV infection did not affect the incidence of HAV seroconversion. No clinical hepatitis was recognized in the subjects who seroconverted. Dual hepatitis A and B virus infection were observed; these were all clinically inapparent. The extraordinary incidence of HAV infection documented in the present study offers an opportunity for vaccine efficacy trials requiring minimal numbers of subjects.     

Viral hepatitis: recent experiences from serological studies in Bangladesh

Infections due to hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV) and hepatitis E (HEV) viruses are the major causes of hepatitis and are associated with significant morbidity and mortality in developing countries like Bangladesh. The present study was carried out to determine the prevalence of HBsAg, anti-HCV antibody, anti-HAV antibody and anti-HEV antibody in patients suspected of having infection by HBV, HCV, HAV and HEV, respectively. Antibody to HAV was detected in 39% of subjects investigated. HBsAg was identified in 19% of subjects. Antibody to HCV and HEV was detected in 13% and 53% subjects, respectively. Infection with HAV was very high among children < or = 6 years of age (100%). On the contrary, exposure to HEV was higher in adult persons > or => 30 years of age (52%) compared to that in children < or = 6 years of age who had 0% incidence. Our study clearly indicates a high prevalence of those viruses, particularly of enterically transmitted HAV and HEV in Bangladesh, which appeared to be a serious health problem in this developing country. Control measures should be taken on an urgent basis to prevent the spread of infections by these viruses.     

Infectious Hepatitis: A 3-Year Retrospective Study at a Tertiary Care Hospital in India

Context: Acute viral hepatitis (AVH) is predominantly caused by hepatitis A virus (HAV) and hepatitis E virus (HEV), the prevalence of which varies in different geographical regions. Aims: This study aimed to determine the prevalence of HAV and HEV infections in patients with AVH, the rate of HAV-HEV co-infection and the prevalence of HEV infection among pregnant women with hepatitis. Settings and Design: It was a retrospective observational study conducted over 3 years from January 2015 to December 2017, after obtaining clearance from the institutional ethics committee. Subjects and Methods: A total of 675 serum samples were collected from patients with a clinical diagnosis of AVH, between January 2015 and December 2017. The study population included outdoor and hospitalised patients between 3 and 70 years of age who presented with signs and symptoms of hepatitis. The presence of IgM anti-HAV and IgM anti-HEV antibodies in serum were assessed by enzyme-linked immunosorbent assay. Statistical Analysis Used: Chi-square test. Results: The prevalence of HAV, HEV and HAV-HEV co-infection was found to be 6.96%, 9.63% and 2.07%, respectively. Among males, this was 7.3%, 8.8% and 2.6%, respectively and in females 6.7%, 10.2% and 1.7%, respectively. However, these differences in the prevalence rates were of no statistical significance. The prevalence of HEV infection in pregnant women with hepatitis was 9.4%. HAV and HEV infections showed a seasonal trend with predominance during summer and rainy seasons (May to September). Conclusions: A higher seroprevalence of HEV as compared to HAV together with a co-infection rate of 2.07% mandates screening for HEV in all suspected cases of acute hepatitis, particularly pregnant women in whom the outcomes of HEV infection are poor. Health and civic authorities should make necessary efforts to counter epidemic or outbreak situations, thus reducing morbidity, mortality and economic burden.     

Prevalence of enterically transmitted hepatitis viruses in patients attending a tertiary--care hospital in south India

The prevalance of enterically transmitted hepatitis viruses, namely, hepatitis A virus (HAV) and hepatitis E virus (HEV) were studied in 404 patients with acute hepatitis attending a tertiary-care hospital in south India. Presence of current HAV/HEV infection was ascertained by the demonstration of IgM antibodies. In 381 patients tested for both agents, HAV IgM was present in 51(13.3%) and HEV IgM present in 66(17.3%). There was dual infection in 3 males (0.8%). HEV infection was seen mostly in older children and adults with only 5.5% occurring in children < 12 years of age. HAV infection was commonly seen to occur in < 12 years of age group (52.7%). One hundred and twenty-six patients were from the Vellore region, among whom HAV and/or HEV aetiology was observed in 28.5%. In this region there did not appear to be any correlation between occurrence of acute hepatitis due to these viruses and rainfall or environmental temperature. Acute hepatitis due to enteric hepatitis viruses was seen throughout the year.     

Excretion of hepatitis A virus in the stools of hospitalized hepatitis patients

A study was carried out to determine whether hepatitis A virus (HAV) can be detected in the stools of patients hospitalized for HAV infection. Acute phase samples of whole blood and stool, as well as completed questionnaires, were obtained from 31 patients hospitalized at any of 13 hospitals in the Phoenix metropolitan area. Blood specimens were tested for hepatitis B surface antigen (HBsAg), IgG antibody to HAV (IgG anti-HAV), and IgM antibody to HAV (IgM anti-HAV). Stools were tested for HAV by radioimmunoassay. Five patients (16.1%) had acute hepatitis B, five (16.1%) had acute non-A/non-B hepatitis, and 21 (67.7%) had acute hepatitis A. Of these 21 patients with acute hepatitis A, 11 (52.4%) were found to have HAV in their stools. These results confirm the potential for infectivity of stools of patients hospitalized for hepatitis A and emphasizes the need for caution when dealing with such stools.     

Etiopathogenetic aspects of hepatitis A. I. Excretion of hepatitis A virus, biochemistry of liver function, and humoral immune response in patients with hepatitis A on admission to hospital

The excretion of hepatitis A virus (HAV) in stools from 30 patients with clinically overt hepatitis A infection on the day of their admission to the hospital was determined and compared with the dynamics and values of biochemical indices of hepatocyte injury as well as with the immune response to HAV. Virus was found in 16 out of 30 stools (53%) collected within 1 week after the appearance of clinical symptoms. In sera obtained on the day of hospitalization both IgM and IgA anti-HAV were detected in all of the 30 patients, while IgG anti-HAV were found in 20 (67%). There was a correlation between HAV excretion and increasing SGPT upon admission to hospital, while the level of SGPT or bilirubin as well as presence or absence of IgG anti-HAV did not correlate with excretion of HAV. HAV from stools was characterized morphologically and physicochemically. The majority of particles visualized by immune electron microscopy had electrondense appearance, while electron-lucid particles were only occasionally encountered. Isopycnic banding of HAV in CsCl revealed a broad range of densities with HAV activity. Rebanding of pooled fractions containing HAV revealed peak amounts of the virus in fractions with densities 1.32-1.33 gm/cm3.     

Survival of hepatitis A and E viruses in soil samples

Survival of hepatitis A virus (HAV) and hepatitis E virus (HEV) in soil samples spiked with respective viruses was analysed using real-time PCR. Virus-spiked soil samples were incubated at environmental temperature (ET) and 37°C and processed weekly. Both HAV and HEV were less stable at fluctuating ET than at 37°C. Of the 403 soil samples collected in the vicinity of Mutha river, India, 19.1% and 4.9% were found to be contaminated with HAV and HEV, respectively.     

Seroepidemiology of hepatitis A virus infection among schoolchildren in Taiwan

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before 1980. The aim of this study was to examine the association between seropositivity of antibodies against HAV (anti-HAV) by a community-based survey. School children from 10 elementary and 3 junior high schools, as well as staff members who worked at the above schools in central Taiwan were selected at random in this study. Anti-HAV was tested in sera of 1,954 healthy schoolchildren (aged 7-15 years old) and 254 teachers by enzyme-linked immunosorbent assay. Schoolchildren had a low prevalence of anti-HAV (2.3%) in contrast to the high seroprevalence in their teachers (52%). The seropositive rates of HAV antibody among the study subjects were increasing with age. No significant differences of anti-HAV seroprevalence among the study subjects were observed when they were stratified by gender, geographical area, household members, and parental education. Whereas, the anti-HAV seroprevalence was significantly higher in schoolchildren who were either aboriginal or living in areas without a supply of drinking tap-water. The seroprevalence of HAV data among the healthy pediatric population would be helpful to evaluate the need for mass vaccination policies.     

Low seroprevalence and zero incidence rate of hepatitis E in men who have sex with men during a hepatitis A outbreak

Hepatitis E virus (HEV) and hepatitis A virus (HAV) are both secreted in feces. Despite HEV transmission in Europe is mainly zoonotic, person-to-person transmission has not been completely excluded. Men who have sex with men (MSM) constitute a high-risk group for HAV mostly due to oral sex. We investigated the potential transmission of HEV during an acute hepatitis A (AHA) outbreak mainly affecting MSM. One hundred and two patients were diagnosed with AHA. Sixty-nine (68%) self-reported to be MSM, 75% of whom had high-risk sexual behaviors and 46% had suffered previous sexually transmitted diseases. We collected serum from 85 (83%) patients during AHA. HEV-IgG seroprevalence was not different among MSM (7%) compared with non-MSM (8%) patients. Two patients had positive anti-HEV-IgM, but all samples tested negative for HEV-RNA. These results suggest that HEV does not spread by sexual contact or person-to-person in our area.     

Identification of genotype 4 hepatitis E virus strains from a patient with acute hepatitis E and farm pigs in Bali, Indonesia

A previous study revealed that antibodies to hepatitis E virus (HEV) (anti-HEV) are highly prevalent among healthy individuals and farm pigs in Bali, Indonesia, and suggested that HEV infection may occur via zoonosis among Balinese people. However, there were no reports of acute hepatitis E in Bali. To elucidate whether Balinese HEV strains recovered from infected humans and pigs have significant sequence similarity, serum samples obtained from 57 patients (age, mean +/- standard deviation, 31.1 +/- 11.9 years) with sporadic acute hepatitis and from one hundred and one 2- or 3-month-old farm pigs in Bali were tested for anti-HEV and HEV RNA. Among the 57 patients, 2 (3.5%) had high-titer IgM/IgA class anti-HEV antibodies and one of them had detectable HEV RNA (BaliE03-46). Overall, 58 pigs (57.4%) tested positive for anti-HEV, while 5 pigs (5.0%) had detectable HEV RNA. Based on the 412-nucleotide sequence within open reading frame 2, the BaliE03-46 isolate and the 5 swine HEV isolates recovered from the viremic pigs were phylogenetically classified in genotype 4, but were only 77.3-90.8% identical to the genotype 4 HEV isolates reported thus far in China, India, Japan, Taiwan, and Vietnam. The BaliE03-46 isolate of human origin shared high identities of 97.3-98.3% with 4 of the 5 Balinese swine isolates, but differed by 16.1% from the remaining swine isolate. These results suggest that indigenous HEV strains of genotype 4 with marked heterogeneity are circulating in Bali, Indonesia, and that pigs are reservoirs of HEV for Balinese people who have a habit of ingesting uncooked pigs.