Harry R Dalton

University of Exeter, Exeter, England, United Kingdom

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Publications (112)936.09 Total impact

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    ABSTRACT: Hepatitis E is hyperendemic in many developing countries in Asia and Africa, and is caused by hepatitis E virus (HEV) genotypes 1 and 2, which are spread via the faecal-oral route by contaminated water. Recent data show that HEV infection is also endemic in developed countries. In such geographical settings, hepatitis E is caused by HEV genotypes 3 and 4, and is mainly a porcine zoonosis. In a minority of cases, HEV causes acute and chronic hepatitis, but infection is commonly asymptomatic or unrecognized. HEV infection is associated with a number of extrahepatic manifestations, including a range of neurological injuries. To date, 91 cases of HEV-associated neurological injury - most commonly, Guillain-Barré syndrome, neuralgic amyotrophy, and encephalitis/myelitis - have been reported. Here, we review the reported cases, discuss possible pathogenic mechanisms, and present our perspectives on future directions and research questions.
    No preview · Article · Dec 2015 · Nature Reviews Neurology
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    ABSTRACT: Background and aims: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. Aim: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. Methods: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. Results: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. Conclusion: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.
    No preview · Article · Dec 2015 · European Journal of Gastroenterology & Hepatology
  • Louisa J Vine · Harry R Dalton
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    ABSTRACT: Hepatotropic viruses are extremely common worldwide and among the most common causes of acute hepatitis and acute liver failure. Seroprevalence rates are high and higher rates are increasingly being found as assays become more sensitive. Most commonly, they present with a viral prodrome and an acute increase in liver enzymes but atypical presentations can occur. Whereas the majority of infections are benign and self-limiting, chronic states do occur, and in the case of Epstein-Barr virus and cytomegalovirus latency occurs after primary infection, with reactivation occurring at later times of illness. Vaccination programmes for hepatitis A, where available, have led to a significant reduction in incidence. Our knowledge of these viruses continues to expand, especially with regard to hepatitis E and its genotypes. Hepatitis E virus has recently been found in donated human blood and the causative agent in some cases of patients presenting with neurology signs and symptoms; it is now considered a significant health burden in both developing and developed countries.
    No preview · Article · Aug 2015
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    Article: Hepatitis E

    Full-text · Article · Jul 2015 · Vox Sanguinis
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    ABSTRACT: The recent earthquakes in Nepal killed thousands, displaced tens of thousands, and destroyed much of the country's infrastructure. Thousands of Nepalis are living in makeshift camps, with limited or no access to clean drinking water. There is now considerable risk of infectious diseases in affected areas.
    Full-text · Article · Jul 2015 · The Lancet
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    ABSTRACT: In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre-existing chronic liver disease (CLD). To determine the role of HEV in patients with decompensated CLD. Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow-up for 6 months or death. IgG seroprevalence was compared with 911 controls. 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28-4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2-30) and Truro (OR 2.5, 95% CI 1.4-4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41-0.86). Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location. © 2015 John Wiley & Sons Ltd.
    No preview · Article · Jul 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries, yet remains under-recognized. In this population-based cohort study, 1,025 randomly selected participants were enrolled from Matlab, Bangladesh (2004-2005). All participants were tested for HEV antibodies and total immunoglobulin (Ig), using an in-house enzyme immunoassay developed by Walter Reed Army Institute of Research (WRAIR). In 2014, we retested the banked sera of 1,009 of those participants using the Wantai anti-HEV IgG enzyme-linked immunosorbent assay (ELISA). The WRAIR assay estimated the overall population seroprevalence as 26.6% (95% confidence interval [CI]: 24.0, 29.5), whereas the Wantai assay produced significantly higher estimated seroprevalence, 46.7% (95% CI: 43.5-49.8) (P < 0.001). However, the two tests give nearly identical findings in those 5 years and under (N = 94) with a 98% agreement between the tests. Retesting populations with modern assays is necessary to establish better population-level estimates of disease burden. © The American Society of Tropical Medicine and Hygiene.
    Full-text · Article · Jul 2015 · The American journal of tropical medicine and hygiene
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    ABSTRACT: Hepatitis E causes a significant burden of disease in developing countries and has recently been increasingly recognized in developed countries. Comparing population anti-hepatitis E virus (HEV) seroprevalence across populations has been difficult. The aim of this study was to compare the anti-HEV IgG seroprevalence in both adults and children in three hyper-endemic areas (Nepal, Bangladesh and southwest France) using a sensitive, commercial anti-HEV IgG assay. Serum or plasma from adults and children in Nepal (n=498), Bangladesh (n=1,009) and Southwest France (n=1031) were tested for anti-HEV IgG using the Wantai assay. After age-standardization, anti-HEV IgG seroprevalence was 47.1%, 49.8% and 34.0% in Nepal, Bangladesh and southwest France, respectively. There was no difference in seroprevalence by gender in any of the countries. A paucity of infections in children 1-10 years-old was consistently observed (less than 15%) at all 3 locations. Surprisingly similar high rates of anti-HEV antibodies were detected using a common, sensitive assay. Despite differences in the epidemiology and circulating genotype of HEV in Nepal, Bangladesh and southwest France, this study found more similarities in population seroprevalence than expected. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015 · Journal of Clinical Virology
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    ABSTRACT: Background: Up to 30% of acute viral hepatitis has no known etiology. To determine the disease etiology in patients with acute hepatitis of unknown etiology (HUE), serum specimens were obtained from 38 patients residing in the United Kingdom and Vietnam and from 26 healthy US blood donors. All specimens tested negative for known viral infections causing hepatitis, using commercially available serological and nucleic acid assays. Methods: Specimens were processed by sequence-independent complementary DNA amplification and next-generation sequencing (NGS). Sufficient material for individual NGS libraries was obtained from 12 HUE cases and 26 blood donors; the remaining HUE cases were sequenced as a pool. Read mapping was done by targeted and de novo assembly. Results: Sequences from hepatitis B virus (HBV) were detected in 7 individuals with HUE (58.3%) and the pooled library, and hepatitis E virus (HEV) was detected in 2 individuals with HUE (16.7%) and the pooled library. Both HEV-positive cases were coinfected with HBV. HBV sequences belonged to genotypes A, D, or G, and HEV sequences belonged to genotype 3. No known hepatotropic viruses were detected in the tested normal human sera. Conclusions: NGS-based detection of HBV and HEV infections is more sensitive than using commercially available assays. HBV and HEV may be cryptically associated with HUE.
    Full-text · Article · Jun 2015 · The Journal of Infectious Diseases

  • No preview · Conference Paper · Jun 2015
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    ABSTRACT: Hepatitis E virus (HEV)-positive plasma donations, identified by a plasma mini-pool screening approach, were analysed using serological methods for the presence of anti-HEV IgM and IgG. Avidity testing was performed on the IgG-reactive donations. Anti-HEV IgG with high avidity was observed in two donors together with high viral loads, but with the absence of anti-HEV IgM. These data are suggestive of re-infection in a small proportion of plasma donors, which has not previously been reported. © 2015 International Society of Blood Transfusion.
    No preview · Article · May 2015 · Vox Sanguinis
  • A Forbes · K L Woolson · H R Dalton

    No preview · Article · May 2015 · Alimentary Pharmacology & Therapeutics

  • No preview · Article · Apr 2015 · Journal of Hepatology

  • No preview · Article · Apr 2015 · Journal of Hepatology
  • B Basnyat · HR Dalton · N Kamar · DB Rein · A Labrique · J Farrar · P Piot · signatories

    No preview · Article · Jan 2015
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    ABSTRACT: Until recently, HEV was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in many developed countries. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan); it mainly affects middle-aged/elderly males; it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viraemic at the time of donation. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggests that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5% and 10% of cases respectively.
    No preview · Article · Jan 2015
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    ABSTRACT: Background Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra-hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied. AimTo report the extra-hepatic manifestations of hepatitis E virus. Methods Retrospective review of data of 106 cases of autochthonous hepatitis E (acute n=105, chronic n=1). ResultsEight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain-Barre syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40years, range 34-92years, P=0.048) and had a more modest transaminitis (median ALT 471IU/L, P=0.015) compared to cases without neurological symptoms [median age 64years (range 18-88years), median ALT 1135IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36months after presenting with acute hepatitis E infection. ConclusionsA range of extra-hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in this UK cohort, and result in significant morbidity which warrants further study.
    No preview · Article · Oct 2014 · Alimentary Pharmacology & Therapeutics
  • Harry R Dalton · Nassim Kamar · Jacques Izopet
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    ABSTRACT: ABSTRACT Hepatitis E virus (HEV) was for many years thought to be found almost exclusively in developing countries, where it is a major health issue. Recent studies have shown that HEV causes acute and chronic infection in developed countries. In these geographical settings, HEV is primarily a porcine zoonosis caused by genotypes 3 (HEV3) and 4 (HEV4). The clinical phenotype of hepatitis E continues to emerge, and recent data show that HEV is associated with a range of neurological syndromes including Guillain-Barré syndrome and neuralgic amytrophy.
    No preview · Article · Oct 2014 · Future Microbiology
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    ABSTRACT: Background & Aims: Upper gastrointestinal hemorrhage (UGIH) is a common cause of hospital admission. The Glasgow Blatchford score (GBS) is an accurate determinant of patients’ risk for hospital-based intervention or death. Patients with GBSs of 0 are at low risk for poor outcome and could be managed as outpatients. Some have therefore proposed extending the definition of low-risk patients by using a higher GBS cut-off value, possibly with an age adjustment. We compared 3 thresholds of the GBS and 2 age-adjusted modifications to identify the optimal cut-off value or modification. Methods We performed an observational study of 2305 consecutive patients presenting with UGIH at 4 centers (Scotland, England, Denmark, and New Zealand). The performance of each threshold and modification was evaluated based on sensitivity and specificity analyses, the proportion of low-risk patients identified, and outcomes of patients classified as low-risk. Results There were differences in age (P=.0001), need for intervention (P<.0001), mortality (P<.015), and GBS (P=.0001) among sites. All systems identified low-risk patients with high levels of sensitivity (>97%). The GBS at cut-offs ≤1 and ≤2, and both modifications, identified low-risk patients with higher levels of specificity (40%−49%) than the GBS with a cut-off of 0 (22% specificity, P<.001). The GBS at cut-off ≤2 had the highest specificity, but 3% of patients classified as low-risk patients had adverse outcomes. All GBS cut-offs, and score modifications, had low levels of specificity when tested in New Zealand (2.5%−11%). Conclusions A GBS cut-off ≤1and both GBS modifications identify almost twice as many low-risk patients with UGIH as a GBS at cut-off of 0. Implementing a protocol for outpatient management, based on one of these scores, could reduce hospital admissions by 15%−20%.
    Full-text · Article · Jul 2014 · Clinical Gastroenterology and Hepatology
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    ABSTRACT: Aim: To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit. Methods: Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction. Results: Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases. Conclusion: In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.
    No preview · Article · Jun 2014 · World Journal of Hepatology

Publication Stats

3k Citations
936.09 Total Impact Points


  • 2011-2015
    • University of Exeter
      Exeter, England, United Kingdom
  • 2001-2015
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom
  • 2014
    • Glasgow Caledonian University
      • Department of Life Sciences
      Glasgow, Scotland, United Kingdom
  • 2012
    • University of Plymouth
      Plymouth, England, United Kingdom
  • 2008-2012
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 2007
    • Auckland City Hospital
      Окленд, Auckland, New Zealand