Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV and HEV infections was investigated serologically and molecularly among 128 consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who contracted acute hepatitis between 1989 and 2005 in a city hospital, and among 416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples collected since the start of hemodialysis or employment, respectively. Between 1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005, however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2 (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two medical staff members (1978 and 2003) in previous studies, none of the 191 hemodialysis patients who had been negative for anti-HAV at the start of hemodialysis contracted HAV infection during the observation period of 7.6 +/- 6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative for anti-HAV at the start of employment acquired hepatitis A during the observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection. Clinical or subclinical HEV infection has occurred rarely during the last three decades, while HAV infection has markedly decreased at least since 1996.     

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.     

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.     

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.     

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.     

Hepatitis E Outbreak in Jaipur due to Genotype IA

Purpose: Suddenly, many cases of fever with jaundice were reported from Sodala area at Jaipur. This outbreak of acute hepatitis at Jaipur Rajasthan was investigated for aetiology and subsequent phylogenetic analysis. Methods: Blood samples were collected from 106 symptomatic patients of acute hepatitis and 39 pregnant females (with or without symptoms of hepatitis) during an outbreak at Jaipur. The samples were tested for hepatitis A virus (HAV) and hepatitis E virus (HEV) by serological and molecular methods (polymerase chain reaction [PCR]). Sequencing of nested PCR product was done for phylogenetic analysis. Hepatitis B surface antigen (HBs antigen), anti-hepatitis C virus (HCV), anti-Leptospira and anti-scrub typhus IgM enzyme-linked immunosorbent assay (ELISA) was done for patients negative for HEV and HAV. Results: Among 106 symptomatic patients, HEV IgM was positive in 84/106 (79.2%) patients and HEV RNA in 72/106 (67.9%) patients. Among pregnant women, 6/39 (15.4%) were HEV IgM positive and 5/39 (12.8%) for HEV RNA. One (2.5%) pregnant woman died due to hepatitis. All the isolates belonged to genotype 1A of HEV. All HAV, HEV-negative samples were negative for HBs antigen, HCV antibody, Leptospira and scrub typhus IgM ELISA. Conclusion: The outbreak was due to HEV genotype 1A. The municipal water supply was contaminated and sanitary conditions and waste disposal were poor in the area. Boiling of drinking water, fixing the water supply pipes and frequent hand washing helped in controlling the outbreak.     

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.     

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.     

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。     

大理地区猪源甲型、乙型、戊型肝炎病毒血清流行病学调查

目的:调查大理地区猪体内甲、乙、戊型肝炎病毒的感染情况。方法:采用酶联免疫吸附实验(ELISA)检测屠宰生猪血清标本甲肝血清标志物(HAV-lgG和HAV-lgM)、乙肝血清标记物(HBsAg,HBsAb,HBeAg,HBeAbHBcAb)、戊肝血清标志物(HEV-lgG和HEV-lgM)。结果:HAV、HBV和HEV的感染率分别为:91%(162/178),93.9%(185/197),23.6%(42/178);HAV和HBV二重感染率为67.97%(121/178);HAV、HBV和HEV三重感染率为20.2%(36/178);HAV和HEV二重感染率为1.7%(3/178);HBV和HEV二重感染率为2.2%(4/178)。结论:甲、乙、戊型肝炎病毒在猪体内存在感染,同时发现在猪体内甲、乙型肝炎病毒重叠感染常见。     

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.     

Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia,prolonged cholestasis,and false-positive immunoglobulin M anti-hepatitis E virus: a case report

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.     

Non-A,non-B hepatitis in Palermo,Western Sicily

Aetiological studies were carried out on 407 cases of acute viral hepatitis during two consecutive years in two general hospitals in Palermo, Sicily. Two hundred ninety-seven showed serological evidence of hepatitis A virus (HAV) infection and 73 of hepatitis B virus (HBV) infection. Of the remaining 37, two had a serologically diagnosed cytomegalovirus hepatitis, while 35 were classified as non-A, non-B (NANB) hepatitis. The frequency of the different major agents of acute viral hepatitis was notably influenced by the age of the patients, HAV being prevalent in children and HBV and NANB in adults. About one-fourth of the adult cases of sporadic, acute viral hepatitis were attributed to NANB virus(es). The acute disease appeared less severe than B hepatitis, as indicated by the duration of jaundice, peak serum bilirubin, and aminotransferase levels. No history of drug addiction or of parenteral exposure to blood or blood products was obtained from the presumed NANB hepatitis patients.     

1995至2000年北京地区散发性急性肝炎患者肝炎病毒抗体的检测与分析

目的 了解北京市地区散发性肝炎患者甲型、乙型、丙型和戊型肝炎病毒感染型别分布及重叠感染。方法 用EIA法检测1995斫2月至2000年12月北京地区散发性急性肝炎患者抗－HAVIgM、HBsAg／抗－HBcIgM、抗－HCVIgM/IgG和抗－HEVIgM/IgG。结果 214例散发性急性肝炎患者血清,抗甲、乙、内和戊型肝炎病毒IgM总阳性数155例,戊型肝炎76例。有9名患者检出2种肝炎病毒抗原或抗体阳性,其中在3名肝硬化患者和2名静脉吸毒者同时检测到HBV和HCV抗原或抗体,1例HBsAg阳性者检测到抗－HAVIgM,3例－HCVIgG阳性者中分别检测到2例抗－HBVIgM和1例抗－HEVIgM。肝炎病毒重叠感染的9名患者年龄在31岁至49岁之间。结论 北京地区散发性急性肝炎78％是由消化道传染的甲戊型肝炎病毒引起,戊型肝炎在四种肝炎中位居首位,其次为甲型肝炎、乙型肝炎和丙型肝炎。肝炎病毒重叠感染多见乙、丙型肝炎病毒合并感染或慢性乙、丙型肝炎患者合并甲型或戊型肝炎病毒感染。在我国对散发性病毒性肝炎的预防应引起高度重视。     

Risk factors and prevalence of hepatitis E in German immigrants from the former soviet union

Worldwide there is only limited information on the epidemiology of hepatitis E virus (HEV) and its association with other hepatotropic viruses. Endemic regions have been described in some Asian countries, whereas in Europe only sporadic cases have been reported. The prevalence of HEV and a series of other viral hepatitis infections was investigated in a group of 1,025 individuals immigrating into Germany from the former Soviet Union. Serum samples were tested for anti-HEV by a commercial enzyme immunoassay (EIA) based on recombinant proteins, and by peptide EIA and immunoblot. Risk factors and other demographic information were investigated using a questionnaire and a short interview. The overall prevalence of anti-hepatitis E antibodies (anti-HEV) was 2.05%. The following risk factors for HEV infection were identified : age of >65 years, resident in the south-west part of the former Soviet Union, history of hepatitis B virus (HBV) infection, and employment in health care professions. HEV prevalence is not strikingly different from that observed in Western European countries. However, the different rates found for HEV vs. hepatitis A virus (HAV) are intriguing, since similar routes of transmission (fecal-oral) are well documented for both viruses. Exposure to HBV is surprisingly high, and the number of hepatitis C virus (HCV)-positive individuals was also higher than those reported from Western European areas. © 1995 Wiley-Liss, Inc.     

Serological markers of hepatitis B, C, and E viruses and human immunodeficiency virus type-1 infections in pregnant women in Bali, Indonesia

Except for hepatitis B virus (HBV), there have been few data on serological markers of hepatitis viruses such as hepatitis C virus (HCV) and E virus (HEV), and human immunodeficiency virus type-1 (HIV) in Bali, Indonesia. During 5 months from April to August 2003, sera were collected from 2,450 pregnant women at eight jurisdictions in Bali, and they were tested for markers of these viruses. Only one (0.04%) was positive for antibody to HCV, but none for antibody to HIV. Hepatitis B surface antigen (HBsAg) was detected in 46 (1.9%) at a prevalence significantly lower than that in 271 of the 10,526 (2.6%) pregnant women in Bali surveyed 10 years previously (P < 0.045). The prevalence of hepatitis B e antigen in pregnant women with HBsAg decreased, also, from 50% to 28% during the 10 years (P < 0.011). Antibody to HEV (anti-HEV) was examined in 819 pregnant women who had been randomly selected from the 2,450. The overall prevalence of anti-HEV was 18%, and there were substantial regional differences spanning from 5% at Tabanan district to 32% at Gianyar district. Furthermore, the prevalence of anti-HEV differed substantially by their religions. In the Sanglah area of Denpasar City, for instance, anti-HEV was detected in 20 of the 102 (20%) Hindus, significantly more frequently than in only 2 of the 101 (2.0%) Muslims (P < 0.001). Swine that are prohibited to Muslims, therefore, is likely to serve as a reservoir of HEV in Bali. In conclusion, HBV is decreasing, HCV and HIV have not prevailed, as yet, while HEV is endemic probably through zoonotic infection in Bali.     

Variation among hepatitis A virus strains. I. Genomic variation detected by T1 oligonucleotide mapping

The genomes of eight hepatitis A virus (HAV) strains originating from far distant geographic regions such as Europe, North Africa, Middle and North America, Australia and The People's Republic of China were compared by RNase T1 oligonucleotide mapping. For this purpose, the viruses were propagated in cell cultures and viral RNA was isolated from highly purified mature virions. It could be shown that variation in nucleotide sequence is common among HAV isolates, but is in the order of magnitude reported for other picornaviruses. For viruses isolated in cell culture directly from stool samples of diseased individuals, changes usually amounted to 1-4% of RNA genome sites. Genomic differences between two virus strains derived from one fecal sample but replicating at either 32 or 37 degrees C were in the same order of magnitude. Thereby, the number of consecutive in vitro passages proved to have only limited influence on the development of genetic variation. For two HAV strains, however, adaptation to and passage in marmosets evidently had imposed highly selective conditions which had favored the appearance of viral genomes differing in up to 75% of their large oligonucleotides (about 10% in sequence) from the oligonucleotide map of a reference HAV strain.     

Presence of enteric hepatitis viruses in the sewage and population of Greater Cairo

In Egypt, the disease burden of viral hepatitis is one of the heaviest worldwide. We conducted a survey of hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients and sewage in Cairo. Our data showed that HAV (genotype IB) was predominant over HEV (genotype 3) and was circulating in the population and the environment.     

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.