Indigenous Hepatitis Research Articles

Molecular Detection of Indigenous Hepatitis E Virus (HEV) from Tibetan Pigs in Tibet, China.

Hepatitis E is an important public health concern throughout the world. Many molecular and serological surveys have reported the prevalence and genotypic characteristics of HEV in humans and animals worldwide. However, the genotypic characterization of this virus is very limited in Tibetan pigs. Hence, we aimed to explore the genotype of HEV, prevailing among Tibetan pigs in China. For this purpose, 253 bile samples of Tibetan pigs (free-range animals) were collected from different slaughterhouses during 2017-2018 and subsequently tested for HEV RNA by RT-nPCR. A total of 11 out of 253 (4.35%) samples tested were positive for HEV RNA. Based on the sequence alignment and phylogenetic analysis, all the isolated HEV strains belonged to genotype 4 and clustered into subtype 4b by sharing more than 84.8-95.2% identities with other reported strains. Our results concluded that HEV genotype 4 is prevailing among Tibetan pigs in Tibet, China.

Indigenous Hepatitis E in England and Wales From 2003 to 2012: Evidence of an Emerging Novel Phylotype of Viruses

Enhanced surveillance and molecular characterisation studies of hepatitis E virus (HEV) in England and Wales have been undertaken since 2003. The dynamics of hepatitis E have changed recently with an increase in the number of indigenous cases and an observed viral shift. HEV antibody and RNA data were analysed to ascertain the annual number of acute infections, the HEV genotype disposition and viral phylogeny. These data were investigated in the context of collected travel history and demographic data. In total, 2713 acute hepatitis E cases were diagnosed, of which 1376 were indigenous infections. Travel associated cases remained steady and mainly associated with Genotype 1 infections. In contrast, major fluctuations were noted in indigenously-acquired cases with a dramatic year on year increase during 2010-2012. Molecular characterisation demonstrated indigenous infections to cluster into two distinct phylogenetic groups with the emergence of a novel group of Genotype 3 viruses coinciding with the recent increase in cases. HEV infection rates are dynamic in England and Wales, influenced by changing trends in indigenously-acquired cases. The recent increase in indigenous cases and the emergence of indigenous viruses not commonly circulating prior to 2010 suggest that the risk of acquiring HEV has changed.

Genotype-4 hepatitis E in a human after ingesting roe deer meat in South Korea

The recent increase in the number of cases of indigenous hepatitis E virus (HEV) infection highlights the importance of identifying the transmission routes for the prevention of such infections. Presented herein is the first case of acute HEV infection after ingesting wild roe deer meat in South Korea. A 43-year-old male presented with abdominal discomfort and jaundice. He had not recently traveled abroad, but had eaten raw roe-deer meat 6-8 weeks before the presentation. On the 7th day of hospitalization the patient was diagnosed with acute viral hepatitis E. Phylogenetic analysis of his serum revealed genotype-4 HEV. This case supports the possibility of zoonotic transmission of HEV because the patient appears to have been infected with genotype-4 HEV after ingesting raw deer meat.

Detection and molecular characterization of hepatitis E virus in clinical, environmental and putative animal sources

Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1%) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100% sequence similarity with human HEV strains.

Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food‐borne transmission of hepatitis E virus and public health concerns

In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health.

Pathogenesis and Treatment of Hepatitis E Virus Infection

Hepatitis E has been considered to be a travel-associated, acute, self-limiting liver disease that causes fulminant hepatic failure in specific high-risk groups only. However, hepatitis E virus (HEV) infection can also be acquired in industrialized countries-HEV genotype 3 infection is a zoonosis, with pigs and rodents serving as animal reservoirs. In recent years, cases of chronic HEV infection that were associated with progressive liver disease have been described in several cohorts of immunocompromised individuals, including recipients of organ transplants. The topic of hepatitis E is therefore re-emerging and has raised the following important questions: what is the risk for HEV infection in Western countries (eg, from eating uncooked meat)? How frequently does chronic hepatitis E develop among human immunodeficiency virus-infected patients and recipients of organ transplants? What are the treatment options? What is the current status of vaccine development? What do we know about the pathogenesis of HEV infection, and why does it have a more severe course in pregnant women? This review summarizes the current knowledge on the pathogenesis and treatment of HEV infection.

Changing Epidemiological Patterns of Hepatitis A Infection in Singapore

Singapore has experienced remarkable socioeconomic progress over the last few decades, with a corresponding rise in standards of sanitation and living conditions. We undertook a study to describe its epidemiological trends of hepatitis A over the last 2 decades. We analysed the epidemiological data on all laboratory-confirmed cases of hepatitis A from 1990 to 2009. We also described 3 outbreaks which occurred in 1991, 1992 and 2002. To determine the changing prevalence of hepatitis A virus (HAV) infection, we compared the findings from a seroepidemiological study conducted in 1993 with earlier surveys in 1975 and 1984/1985. The incidence of indigenous hepatitis A cases per 100,000 population declined significantly from 1.8 in 1989 to 0.7 in 2009, and more than half were imported. While majority of the imported cases were Singapore residents, the proportion of imported cases among Singapore residents had decreased significantly. Most of the Singapore residents contracted the disease from Southeast Asia and the Indian subcontinent. The overall prevalence of HAV infection in the population declined from 31.8% in 1984/85 to 25.9% in 1993. The incidence and seroprevalence of hepatitis A in Singapore are comparable to other developed countries. As Singapore is situated in a region highly endemic for HAV, it is very vulnerable to the introduction of the disease because of the high volume of regional travel and import of food, especially shellfish. While we note that there have been no further shellfish-associated outbreaks since 2002, sustained vigilance, strict control of food import by the authorities and public health education on the risk of consuming shellfish, especially cockles, raw and half-cooked, should be maintained.

Seroprevalence of Hepatitis E Virus in the UK Farming Population

Hepatitis E is a zoonosis that can be acquired by the consumption of contaminated food or water, or via person-to-person spread. However, little is known about the transmission of hepatitis E virus (HEV) in the UK. We investigated the epidemiology of indigenous hepatitis E infection using the PHLS Farm Cohort, a sentinel group with a history of close contact with a range of domestic animals. Ten of the 413 subjects tested were positive for hepatitis E IgG antibodies (2.4%). Seroprevalence peaked in those aged 51 to 60 years (relative risk 3.3, 95% CI: 1.0-10.5). Male participants (relative risk 3.6, 95% CI: 0.6-21.2) and those from farms in the Hereford area of the United Kingdom (relative risk 2.7, 95% CI: 0.8-8.4), an area of mixed livestock farming, were more likely to have serological evidence of previous HEVs exposure, although these findings were not statistically significant. Exposure to pigs, or water from a private supply, was not identified as a significant risk factor. The results of this study suggest that UK farming populations are exposed to HEV, but the predominant route of transmission remains elusive.

Indigenous hepatitis E virus infection of a plasma donor in Germany

Although Europe is supposed to be non-endemic for hepatitis E virus (HEV), locally acquired human cases are registered, and a relatively high prevalence for anti-HEV was found in blood donors in some European countries. Transfusion-transmitted infections by contaminated blood products were reported in Japan and sporadically in Europe. Several samples from a plasma donor were screened with a highly sensitive quantitative HEV real-time polymerase chain reaction and the full-length genome was generated. Serology was performed with two different commercially available ELISA kits. The full-length genome sequence of human HEV was identified using samples from a plasma donor with acute self-limiting hepatitis. Plasma donated 2 weeks before onset of elevated liver enzyme levels was already positive for HEV RNA (10(4) copies/ml). High viraemia (10(6) copies/ml) correlated with the detection of anti-HEV IgM in the first blood sample with increased alanine transaminase levels. Phylogenetic analyses grouped the isolate within genotype 3, subtype 3f. The sequence analyses and the epidemiological data revealed that the plasma donor was most probably infected with a swine HEV. This case supports the ongoing discussion of an obligatory HEV nucleic acid testing of blood products for special recipient risk groups.

Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan

Recent studies have shown that indigenous hepatitis E virus (HEV) strains cause hepatitis E in industrialized countries. We aimed to clarify the characteristics of HEV infection in sporadic hepatitis patients during the last decade in Miyagi, northeast Japan. We analyzed 94 serum samples obtained from acute or fulminant hepatitis patients of non-A, non-B, and non-C etiology between 1999 and 2008. Antibody to HEV (anti-HEV) was assayed, and patients who were positive for IgM- and/or IgA-class anti-HEV were diagnosed with hepatitis E. HEV RNA was tested in these patients, and phylogenetic analysis was performed. The occurrence of hepatitis E was compared with that of hepatitis A. Eight acute hepatitis patients (8.5%) were diagnosed with hepatitis E, and HEV RNA was detectable in seven patients. Five isolates of HEV were segregated into genotype 3 and the remaining two isolates into genotype 4. The year of the occurrence of hepatitis E was distributed almost equally from 1999 to 2008, whereas the cases of acute hepatitis A (n = 16) have decreased markedly in the last several years. In 2004-2008, the occurrence of hepatitis E was greater than that of hepatitis A (five cases vs. one case). As for seasonality, hepatitis E occurred more frequently from September to December than hepatitis A (five cases vs. four cases), although less frequently from January to April (one case vs. seven cases). The occurrence of hepatitis E has not decreased during the last decade in northeast Japan, in contrast to hepatitis A.

Indigenous hepatitis E virus infection in England: More common than it seems

Background Indigenous hepatitis E virus (HEV) is increasingly diagnosed in England due to a better awareness and understanding of the virus. However, the true burden of infection and therefore its implication to public health remains undefined. Objectives To estimate the HEV seroprevalence in the general population and to investigate how the risk of HEV infection had fluctuated over time. Study design Two sample collections stratified by age ranging from 1 to 80 years, were screened for HEV IgG antibody. The two collections were separated by 13 years enabling the average incidence between 1991 and 2004 to be estimated. Additional force of infection calculations were also undertaken. Results An overall HEV antibody prevalence of 13% was determined, increasing with age and peaking at 25% in those aged over 50 years. Analysis of the two sample collections demonstrated a temporal shift in seroprevalence indicating that the risk of acquiring HEV infection was not solely age dependant. Data showed that the force of infection had been particularly high in the middle of the 20th century but had subsequently decreased. Current HEV incidence estimates revealed that the incidence did not vary in different age groups. Conclusions This study indicated a high anti-HEV seroprevalence in England and that there was a period of increased risk of acquiring HEV infection which has now decreased. Incidence estimates show that shared risk factors still exist for acquiring HEV infection across all age groups in England.

Hepatitis E Virus Genotype 1, Cuba

Hepatitis E Virus Genotype 1, Cuba

A national survey of acute hepatitis E in France

Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

Swine‐like hepatitis E viruses are a cause of unexplained hepatitis in the Netherlands

Hepatitis E virus (HEV) infections in developed countries are recognized as an imported disease related to travel to endemic regions. However, increasing evidence suggests that HEV infection may also occur in the developed countries and that swine may act as a possible reservoir. To investigate the indigenous transmission of HEV in the Netherlands, sera from 50 blood donors and 1027 sera from patients with acute hepatitis were screened with an ELISA for HEV-specific IgG and IgM. Because the Netherlands is considered a nonendemic region, all positive ELISA results were confirmed by immunoblot to exclude false-positive results. Evidence of recent HEV infection was detected in 0% of the blood donors and 4.4% of the cases, based on combined positive IgM and IgG responses. The serodiagnosis was confirmed by a positive polymerase chain reaction (PCR) in 24 patients with hepatitis (2.3% overall, 51% of confirmed IgM+/IgG+ cases). IgG antibodies alone were detected in 4.2% of patients. We found related sequences to virus strains detected in Dutch pigs (genotype 3, 91-97% homology) in 89% of PCR-confirmed HEV patients. The detection of unique swine-like HEV sequences in 16 indigenous hepatitis patients without a recent travel history suggests that HEV is endemic in the Netherlands. We recommend including HEV tests in unexplained acute hepatitis patients, despite their travel history.

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

Transfusion‐transmitted hepatitis E in a ‘nonhyperendemic’ country

Indigenous hepatitis E is increasingly recognized in developed countries, where it may be a zoonosis. We describe the first case of transfusion-transmitted hepatitis E in the UK from a blood donor who had no history of recent travel abroad. Follow-up of the donor and recipients of the blood products was carried out using serological and molecular techniques. Acute hepatitis E was transmitted to one of two recipients. The infected patient would have received a larger volume of the donor's plasma. HEV subgenomic sequences carried by the donor and recipient were identical. This is the first case of post-transfusion hepatitis E in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic country may occur by blood transfusion. It is important that blood donors inform the transfusion service of all post-donation illnesses so that appropriate interventions can take place.

Removal of hepatitis A virus from water by polyacrylonitrile-based ultrafiltration membranes

Ultrafiltration-based polyacrylonitrile membranes (UF-membranes) were evaluated for their ability to retain tissue culture adapted indigenous hepatitis A virus from water. Amicon cell (dead-end ultrafiltration unit)-based experiment was set up and viral assay was carried out using rapid and sensitive reverse transcriptase polymerase chain reaction (RT-PCR). The RT-PCR results show retention of virus particles by the polyacrylonitrile membranes. A protocol for routine virological evaluation of membranes is described and the use of these membranes for water purification units and for virus concentration systems for field application is discussed.

Present state of hepatitis E virus epidemiology in Tokyo, Japan

Recently studies have reported the possibility that an indigenous hepatitis E virus (HEV) exists in Japan, but the epidemiological features of HEV in Japan are inadequate to make a judgment. In order to search the present state of HEV infection in Japan, we used ELISA to test 1033 sera from residents living in Tokyo and the Tokyo suburbs, for the presence of the antibody against HEV. The positive rate of anti-HEV IgG was 15.4% in all liver disease patients (68 of 440), 3% (6/200) in healthy individuals and 0.4% in infants (1/246), respectively ( P<0.01). Anti-HEV IgG was seen in 17.6% (35/199) of liver disease patients of unknown etiology; 29.4% (5/17) of fulminant hepatitis, 17% of acute hepatitis (15/88) and 16% of chronic hepatitis (15/94). Anti-HEV IgG co-existed with hepatitis B virus and hepatitis C virus in 23.6% (21/89) and 7.9% (12/152), respectively. Furthermore, the prevalence of anti-HEV IgG was significantly higher in hemodialysis patients (18/60: 30%) and hospital workers (8/87: 9.2%) than in the healthy population ( P<0.01). Anti-HEV IgM was detected in 0.1% of all samples tested (1/1033). The prevalence of anti-HEV IgG increased with age. No individuals with HEV antibody had a recent history of visiting countries where hepatitis E is endemic. These results indicate that generally 15.4% of Japanese patients with liver diseases had a history of HEV infection in the past. The routes of transmission of HEV require clarification in Japan.

Partial sequence analysis of indigenous hepatitis E virus isolated in the United Kingdom

The first nucleotide sequences of hepatitis E virus (HEV) acquired in the United Kingdom are described. The sequences are novel and are related most closely to HEV isolated from Greece (Greece 2 strain), consistent with their having been derived from an indigenous European virus. HEV was assumed until recently to be rare in the United Kingdom and other industrialised countries and, consequently, hepatitis E may be under-diagnosed in industrialised countries.