Malcolm Banks

Hepatitis E: an emerging infection in developed countries

Hepatitis E is endemic in many developing countries where it causes substantial morbidity. In industrialised countries, it is considered rare, and largely confined to travellers returning from endemic areas. However, there is now a growing body of evidence that challenges this notion. Autochthonous hepatitis E in developed countries is far more common than previously recognised, and might be more common than hepatitis A. Hepatitis E has a predilection for older men in whom it causes substantial morbidity and mortality. The disease has a poor prognosis in the context of pre-existing chronic liver disease, and is frequently misdiagnosed as drug-induced liver injury. The source and route of infection remain uncertain, but it might be a porcine zoonosis. Patients with unexplained hepatitis should be tested for hepatitis E, whatever their age or travel history.

Non–Travel-Associated Hepatitis E in England and Wales: Demographic, Clinical, and Molecular Epidemiological Characteristics

Between 1996 and 2003, 186 cases of hepatitis E were serologically diagnosed. Of these, 17 (9%) were not associated with recent travel abroad. Patients were >55 years old (range, 56-82 years old) and tended to be male (76%). Two patients presented with fulminant hepatitis. A total of 129 (69%) cases were associated with recent travel to countries where hepatitis E virus (HEV) is hyperendemic. Compared with patients with travel-associated disease, patients with non-travel-associated disease were more likely to be older, living in coastal or estuarine areas, not of South Asian ethnicity, and infected by genotype 3 strains of HEV. The genotype 3 subgenomic nucleotide sequences were unique and closely related to those from British pigs. Patients infected by HEV indigenous to England and Wales tended to belong to a distinct demographic group, there were multiple sources of infection, and pigs might have been a viral reservoir.

Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease.

Aims To report the natural history of autochthonous hepatitis E and hepatitis E virus (HEV) IgG seroprevalence in Southwest England. Methods Patients with unexplained hepatitis were tested for hepatitis E and cases followed until recovery or death. Five hundred blood donors, 336 individuals over the age of 60 years and 126 patients with chronic liver disease were tested for HEV IgG. Results Forty cases of autochthonous hepatitis E (genotype 3) were identified. Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant complication and three patients died, two of who had previously undiagnosed cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and summer and no cases in November and December. HEV IgG prevalence increases with age, is more common in men and is 16% in blood donors, 13% in patients with chronic liver disease and 25% in individuals over 60 years. Conclusion Autochthonous hepatitis E is more common than previously recognized, and should be considered in the differential diagnosis in patients with hepatitis, whatever their age or travel history. It carries a significant morbidity and when seen in the context of chronic liver disease carries an adverse prognosis.

Autochthonous hepatitis E in southwest England

Summary.  Although autochthonous hepatitis E has been reported in developed countries, its extent and nature in the United Kingdom are unclear. The aim of the present study was to report the natural history, lifestyle risk factors and molecular epidemiology of autochthonous hepatitis E infection in southwest England. Three hundred and thirty‐three patients with unexplained hepatitis were tested for markers of hepatitis E virus (HEV) infection over a 7‐year period. HEV RNA isolated from the cases was amplified and characterized. Of the 333 patients, 21 had autochthonous hepatitis E. Patients were middle‐aged or elderly and males were more commonly affected. Clinical manifestations ranged from asymptomatic infection to severe hepatitis. Of the 21 patients, 20 recovered within 6 weeks. None of the cases had travelled to an area endemic for HEV. None of the patients were vegetarian and all ate pork. Of the 21 cases, 20 occurred in the spring, summer and autumn months. All polymerase‐chain‐reaction‐confirmed cases carried HEV genotype 3, which bore close sequence homology to HEV circulating in UK pigs. In the United Kingdom, autochthonous hepatitis E may be more common than previously recognized. Although the mode of transmission remains to be determined, it may be a zoonosis with pigs as a reservoir. Hepatitis E should be considered a public health issue in the United Kingdom.

Human and Porcine Hepatitis E Virus Strains, United Kingdom

We describe a case of acquired infection of a strain of hepatitis E virus (HEV)with a 100% amino acid identity to the analogous region in strains of HEV circulating in a United Kingdom pig herd. This case further supports the theory that autochthonous HEV infection in industrialized countries is zoonotic.

Hepatitis E Virus in Pork Food Chain, United Kingdom, 2009–2010

We investigated contamination by hepatitis E virus (HEV) in the pork production chain in the United Kingdom. We detected HEV in pig liver samples in a slaughterhouse, in surface samples from a processing plant, and in pork sausages and surface samples at point of sale. Our findings provide evidence for possible foodborne transmission of HEV during pork production.

Hepatitis E Virus in Pork Liver Sausage, France

We investigated viability of hepatitis E virus (HEV) identified in contaminated pork liver sausages obtained from France. HEV replication was demonstrated in 1 of 4 samples by using a 3-dimensional cell culture system. The risk for human infection with HEV by consumption of these sausages should be considered to be high.

Prevalence and transmission of hepatitis E virus in domestic swine populations in different European countries

BackgroundHepatitis E virus (HEV) genotype 3 and 4 can cause liver disease in human and has its main reservoir in pigs. HEV investigations in pigs worldwide have been performed but there is still a lack of information on the infection dynamics in pig populations.FindingsThe HEV transmission dynamics in commercial pig farms in six different European countries was studied. The data collected show prevalence in weaners ranging from 8% to 30%. The average HEV prevalence in growers was between 20% and 44%. The fatteners prevalence ranged between 8% and 73%. Sows prevalence was similar in all countries. Boar faeces were tested for HEV only in Spain and Czech Republic, and the prevalence was 4.3% and 3.5% respectively. The collected data sets were analyzed using a recently developed model to estimate the transmission dynamics of HEV in the different countries confirming that HEV is endemic in pig farms.ConclusionsThis study has been performed using similar detection methods (real time RT-PCR) for all samples and the same model (SIR model) to analyse the data. Furthermore, it describes HEV prevalence and within-herd transmission dynamics in European Countries (EU): Czech Republic, Italy, Portugal, Spain, The Netherlands and United Kingdom, confirming that HEV is circulating in pig farms from weaners to fatteners and that the reproductive number mathematical defined as R0 is in the same range for all countries studied.

Characterization of the DNA Polymerase Loci of Porcine Cytomegaloviruses from Diverse Geographic Origins

Porcine cytomegalovirus (PCMV) is an undesired pathogen in pigs intended for use as organ donors in xenotransplantation. In the present work, we characterized the first set of genes of PCMV. From a German isolate, the DNA polymerase (DPOL) locus was amplified and two complete open reading frames (ORF) as well as two partial ORFs including the complete DPOL gene and the 3′-end of the glycoprotein gB gene were sequenced. The deduced amino acid sequences showed the highest identities with the respective proteins of the betaherpesviruses, in particular those (ORFs 36–39) of the human herpesviruses 6 and 7 (HHV-6 and -7). In phylogenetic analysis, PCMV clustered also with HHV-6 and HHV-7. On this basis, PCMV could be firmly classified to the Betaherpesvirinae and tentatively assigned to the genus Roseolovirus. In addition to the German isolate, the DPOL gene was analysed from a British and a Japanese strain as well as a Spanish isolate. Differences of 0.4 to 1% were found on the nucleotide and the amino acid level. On the basis of the conserved regions, primer pairs were selected for PCR which detected PCMV in blood and tissue samples from four European countries. Therefore, these are the first nucleic acid-based test systems which were shown to universally detect PCMV. The application of these assays to organs of domestic pigs from Germany revealed a PCMV prevalence of >50%.

Replication of hepatitis E virus in three-dimensional cell culture.

Hepatitis E is an acute, viral hepatitis epidemic in developing regions, but which is detected with increasing frequency in sporadic form in developed regions. Pigs and possibly some other mammals are considered reservoirs of zoonotic infection with hepatitis E virus (HEV). However, whilst the relative significance of potential transmission routes from pigs to people is still unclear, the consumption of raw or undercooked pig meat has been implicated as a source of HEV infection. The lack of information about HEV zoonotic transmission is due in part to the difficulties of in vitro propagation of HEV. The Rotating Wall Vessel (RVW) has been described as a useful tool for the culture of cell lines in a 3-dimensional (3D) configuration. The aim of this work was to develop a 3D cell culture system for HEV to facilitate studies into the viability of virions contaminating pig tissues. This study, demonstrated that HEV can replicate efficiently in the RWV in human hepatoblastoma PLC/PRF/5 cells for up to 5 months not only by real time RT-PCR but also by detection of complete virions via electron microscopy. Furthermore, the replication of HEV progeny was observed by detecting HEV RNA by RT-PCR. The progeny were able to infect fresh 3D cultures, showing that this method is able to produce infectious hepatitis E virions.