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.     

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.     

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.     

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。     

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.     

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.     

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.     

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.     

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.     

A simple method for clonal selection of hepatitis A virus based on recovery of virus from radioimmunofocus overlays

Hepatitis A virus (HAV), a non-cytopathic picornavirus, has been quantitated in cell culture by autoradiographic detection of foci of viral replication developing beneath an agarose overlay following fixation and 'staining' of the cell sheet with radiolabelled antibody (radioimmunofocus assay). Using a modification of this basic technique, a clonal variant of HM-175 strain HAV was isolated from agarose overlying individual radioimmunofoci. Virus recovered from the agarose was amplified in small volume cultures of BS-C-1 cells and identified in supernatant culture fluids by cDNA-RNA hybridization. No virus was recovered from agarose which did not overlie a focus of viral replication. This method offers a simple, yet relatively rapid and certain means of selecting clonal variants of non-plaquing viruses such as hepatitis A virus.     

Non-A, non-B hepatitis in chimpanzees: interference with acute hepatitis A virus and chronic hepatitis B virus infections

Two chimpanzees with persistent non-A, non-B (NANB) hepatitis were superinfected with marmoset-passaged MS-1 HAV. Two control chimpanzees were also infected with marmoset-passaged HAV. Neither animal with persistent NANB hepatitis developed elevated alanine aminotransferase (ALT) activity, whereas both control chimpanzees exhibited ALT elevations within 3 weeks after inoculation. In addition, both NANB-infected chimpanzees demonstrated a delayed anti-HAV antibody response in which one animal failed to produce detectable IgM anti-HAV. With the exception of one stool, all serial liver biopsy specimens and daily stool suspensions from the superinfected chimpanzees were negative for HAV antigen. One chimpanzee with a chronic HBV infection was superinfected with non-A, non-B hepatitis and was shown to develop elevated ALT activity and hepatocyte ultrastructural alterations accompanied by a marked reduction in the titer of serum HBsAg. Our combined findings indicate that acute and persistent non-A, non-B hepatitis infections are capable of interferring with two distinctly different hepatotropic viruses. These results also suggest that in vitro detection of non-A, non-B hepatitis infection or virus(es) may be achieved by antibody-independent methodologies that employ the basic principle of viral interference.     

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.     

Hepatitis A and Hepatitis E: Clinical and Epidemiological Features,Diagnosis, Treatment,and Prevention

Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.     

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.     

From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety

Hepatitis E virus (HEV) is an important but extremely understudied pathogen. The mechanisms of HEV replication and pathogenesis are poorly understood, and a vaccine against HEV is not yet available. HEV is classified in the family Hepeviridae consisting of at least four recognized major genotypes. Genotypes 1 and 2 HEV are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 HEV are zoonotic and responsible for sporadic cases worldwide. The identification and characterization of a number of animal strains of HEV from pigs, chickens, rabbits, rats, mongoose, deer, and possibly cattle and sheep have significantly broadened the host range and diversity of HEV. The demonstrated ability of cross-species infection by some animal strains of HEV raises public health concerns for zoonotic HEV infection. Pigs are a recognized reservoir for HEV, and pig handlers are at increased risk of zoonotic HEV infection. Sporadic cases of hepatitis E have been definitively linked to the consumption of raw or undercooked animal meats such as pig livers, sausages, and deer meats. In addition, since large amounts of viruses excreted in feces, animal manure land application and runoffs can contaminate irrigation and drinking water with concomitant contamination of produce or shellfish. HEV RNA of swine origin has been detected in swine manure, sewage water and oysters, and consumption of contaminated shellfish has also been implicated in sporadic cases of hepatitis E. Therefore, the animal strains of HEV pose not only a zoonotic risk but also food and environmental safety concerns.     

Analysis of the circulation of hepatitis A virus in Argentina since vaccine introduction

Hepatitis A virus (HAV) has shown intermediate endemicity in Argentina, but its incidence has decreased since vaccine introduction in 2005. Environmental surveillance was conducted in five rivers from Argentina from 2005 to 2012, complementing clinical information. HAV detection decreased since 2005, although its circulation continues, maintaining viral diversity but not undergoing antigenic drift. Most sequences belonged to subgenotype IA, closely related to Argentinean clinical sequences, but one belonged to proposed subgenotype IC, previously undetected in the country. Environmental surveillance might contribute to monitoring the single-dose vaccination schedule, representing not only strains causing disease but also the circulating population and the viral introductions.     

Virus-binding activity of fibronectin: masking of hepatitis A virus

Human plasma fibronectin interacts with viruses. When fibronectin-containing human sera negative for antibodies to hepatitis A virus (HAV) were added to suspensions of HAV, radioimmunological detection of HAV was reduced. This masking effect seemed to depend on the fibronectin concentration of the sera: plasma fibronectin purified by cryoprecipitation and affinity chromatography showed a masking effect on purified HAV which was dependent on the concentrations of fibronectin and HAV. Fibronectin peptides were obtained by subtilisin digestion: the non-collagen-binding regions of the fibronectin molecule were involved in the binding of HAV. We conclude that fibronectin has a virus-binding activity which interferes with radioimmunological methods for virus detection, and may contribute to the frequent transmission of hepatitis viruses by blood products enriched in fibronectin.     

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.