World Journal of Cardiovascular Diseases, 2013, 3, 519-522 WJCD Published Online November 2013 (
Hepatitis E is more common than hepatitis A among
returning travellers presenting to tertiary care
Catherine Cosgrove1, Margaret Armstrong1, Mike Kidd2, Michael Brown1, Tom Doherty1
1Hospital for Tropical Diseases, London, UK
2The Department of Virology, University College Hospitals London, London, UK
Received 15 August 2013; revised 25 September 2013; accepted 4 October 2013
Copyright © 2013 Catherine Cosgrove et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction: Acute viral hepatitis is a relatively
common infection resulting in hospital attendance
after foreign travel. Travellers and doctors are gen-
erally aware of hepatitis A and the fact that safe and
effective immunisation is available. In contrast, there
is no widely available vaccine for hepatitis E and most
physicians’ experience with this condition is limited.
Over the last few years, the number of cases of hepati-
tis E has increased. Meth ods: We exam ined th e pr ev a-
lence of hepatitis A and E among patients presenting
to the Hospital for Tropical Diseases between 2000
and 2009. Travel history, demographics and labora-
tory parameters of these patients were compared.
Results: The annual incidence of hepatitis A re-
mained static, while that of hepatitis E increased from
1 to 4. Hepatitis E was associated with older age,
travel to the Indian sub-continent (ISC), and visiting
friends and relatives (VFR). Peak ALT was similar
between patients with hepatitis A or E, but as many
as a third of those with hepatitis E developed a pro-
longed INR, compared to 11% of those with hepatitis
A. In addition, patients with hepatitis E had a longer
hospital admission by a median of 3 days. Conclusion:
Hepatitis E is now the commonest cause of faeco-oral
viral hepatitis at this centre, and is associated with
laboratory features suggestive of more severe liver
damage and longer hospital stay.
Keywords: Hepatitis; Returning Traveller
Hepatitis A and E are both transmitted via the faeco-oral
route; both are usually self-limiting but may cause a ful-
minant hepatitic picture.
There are around 400 cases of hepatitis A reported to
the Health Protection Agen cy (HPA) in the United King-
dom each year. This has fallen dramatically from the
peak observed in the late 1980s and early 1990s when
there were up to 8000 cases [1]. There is an estimated
risk of acquiring hepatitis A of 0.05% for each visit to an
endemic country [2], most commonly among young
adults. The mean incubation period is 28 days. Severity
of infection increases with age and fulminant hepatitis is
seen in approximately 1% of cases [1]. Seroprevalence
data suggest that most people below the age of 50 in the
UK are susceptible. Immunisation is recommended for
high-risk groups such as sewage workers and people
over the age of five travellin g to an endemic country [3].
The vaccine is a formaldehyde inactivated virus with an
efficacy around 95% after two doses [3].
Hepatitis E is also transmitted faeco-orally. Until re-
cently it was thought to be predominately an imported
disease. It is most likely a zoonosis originating in pigs
[4]. There are four major genotypes (1-4). The HPA re-
ports about 200 cases of hepatitis E each year, with a peak
of 326 in 2005 [5]. Approximately 10% acquired their
infection in the UK and were predominantly older men
who had direct contact with pigs. The principal genotype
in domestic infection is genotype 3, rather than geno-
types 1 and 2, which are the most common imported
strains. There is no widely available vaccine for hepatitis
E although several recent trials have been published
[5-7], the most recent of which suggested a vaccine effi-
cacy approaching 100%.
In order to get a better understanding of the prevalence
of hepatitis E, we conducted a retrospective analysis of
all cases of acute faeco-oral hepatitis among adults pre-
senting to the Hospital for Tropical Diseases (HTD) over
9 years.
All patients seen at the HTD between August 2000 and
C. Cosgrove et al. / World Journal of Cardiovascular Diseases 3 (2013) 519-522
February 2009 who had serologically confirmed diagno-
ses of hepatitis A or hepatitis E were included. Demo-
graphic and travel data were collected prospectively and
laboratory and clinical data were collected retrospec-
tively for these cases.
There were 21 cases of hepatitis A diagnosed, (16 ad-
mitted, five treated as outpatients). Twenty-two patients
with hepatitis E were admitted and seve n were treated as
outpatients. Twenty were confirmed and two were prob-
able where the IgM for hepatitis E was weakly reactive
but the clinical presentation was typical. The year of di-
agnosis of these patients is shown in Figure 1.
2.1. Demographics
Both hepatitis A and hepatitis E were more common in
men (18/29 [62%] and 15/21 [71%] respectively). The
average age of patients with hepatitis A was 27.9 years
(24.6 - 35.5) compared to 34.6 years (29.2 - 47.6) for
hepatitis E. (Table 1).
Of the 21 patients with hepatitis A, three were Asian,
nine Caucasian, two “other” and seven declined to give
this information. Ten were born in Europe, two in South
America, two in India, one in Saudi Arabia and six pa-
tients declined to give these data.
Nineteen out of 29 (65%) patients with h epatitis E de-
scribed themselves as Asian, eight as Caucasian and two
declined to give an ethnicity. Eleven were born in the
Indian subcontinent, eight in the UK, four in other parts
of the world and six declined to give this information.
2.2. Travel History
Most patients with hepatitis E acquired their infection
while visiting the Indian sub-continent (ISC): 11 in India,
10 in Bangladesh, three in Pakistan, and two who had
extensive travel across SE Asia and the ISC. Only three
patients had travelled to other parts of the world (Af-
ghanistan, Latin America, and Sudan). Most patients who
acquired hepatitis E (15/29) had travelled to visit family.
One patient from the ISC was visiting relatives in the UK
when they became unwell; one was a new immigrant
from the area; one was a returning UK expatriate; five
were holidaymakers; two were working abroad and for
four patients the reason for travel was not documented.
In contrast, fewer th an half of p atients with h epatitis A
had travelled to the ISC (four India, one Pakistan, one Sri
Lanka). Six had travelled elsewhere (Egypt, Senegal,
Madagascar, Colombia, Ghana, and Nigeria). Seven ac-
quired their infection in the UK and travel history was
not documented for two (Tab le 1 and Figure 2). Among
patients with hepatitis A four went on holiday; two had
visited family; two were teaching abroad; one was a for-
eign visitor; one a recent immigrant to the UK; one had
been studying abroad, and data were not collected in
Ta bl e 1 . Demographic characteristics of patients with hepatitis
A and E.
Hepatitis A Hepatitis E
No. of cases 21 29
Male to female ratio 2.5:1 1.6:1
Age-median (IQR) 27.9 (24.6- 35.5) 34.6 (29.2 - 47.6)
Indian subcontinent (%) 30 90*
Visiting friends and relations (%)10 55*
*Chi squared p < 0.0001 (hepatitis A compared with hepatitis E).
2000 2001 2002 2003 2004 2005 2006 2007 2008
Number of Cases
Hepatitis E
Hepatitis A
Figure 1. Cases of hepatitis A and E by year of diagnosis.
2.3. Clinical and Biochemical Data
The mean length of admission was significantly longer in
those with hepatitis E (5.4 days) compared with those
with hepatitis A (2.4 days) (Ta b l e 2 ). There was no dif-
ference in transaminitis between patients with hepatitis A
(ALT mean 2953 IU/L, maximum 6577 IU/L) and hepa-
titis E (ALT mean of 2691 IU/L and maximum 8887
IU/L). Jaundice was similar between the two groups
(hepatitis A patients had a mean bilirubin 174 IU/L
maximum 737 IU/L, hepatitis E patients bilirubin mean
187 IU/L maximum 522 IU/L,).
INR was more likely to be prolonged among the pa-
tients with hepatitis E (INR greater than 1.2 in 9/26 (35%)
in hepatitis E and 2/19 (10% ) in hepatitis A (Table 2)).
Pregnancy did not appear to be a risk factor; only one
patient in this cohort was pregnant and she had hepatitis
A. Four patients, all with hepatitis E had an additional
infection: ascaris lumbricoides, mycoplasma, paraty-
phoid and Strongyloides stercoralis.
Hepatitis E is a non-enveloped spherical RNA virus that
is classified as a Hepevirus with four genotypes [8]. The
first outbreaks of hepatitis E were recognised in the early
1980s with the virus only identified in 1983 [9]. It is an
enterically transmitted virus common in areas with poor
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C. Cosgrove et al. / World Journal of Cardiovascular Diseases 3 (2013) 519-522 521
Table 2. Clinical and biochemical data.
Hepatitis A Hepatitis E
Peak ALT (mean) 2953 2691
Peak bilirubin (mean) 174 187
INR > 1.2* 2/19 (12) 9/26 (35)
Length of Stay if admi t ted (days) 2.4 5.4
*Chi squared p < 0.0001 (hepatitis A compared with hepatitis E); Mann-
Whitney t est p < 0.0006.
All over SE Asia
Latin America
3% Sudan
Sri Lanka
Latin America
No Travel
Figure 2. Country of travel for patients with (a) hepatitis E and
(b) hepatitis A.
sanitation, particularly Asia. Outbreaks have also been
seen in industrialised countries where pigs are a reservoir
and cases are thought to be linked to animal husbandry,
although in other cases the source has been difficult to
verify [10]. In resource-poor countries, infection is usu-
ally acquired in early adult life, which contrasts with
hepatitis A that is invariably acquired in childhood. In
studies from the UK, infection was more common in
older men [11,12]. Hepatitis E is usually a mild , self lim-
iting illness except among pregnant women, immuno-
suppressed individuals or those with underlying liver
disease [6]. However in a series of 17 patients who con-
tracted hepatitis E in the UK, two developed fulminant
liver failure, one of whom required a liver transplant,
while the other died [10]. Data from India suggest that
pregnant women are more susceptible to severe disease,
but the fatality rate was not increased compared to those
who were not pregnant [13]. While both hepatitis A and
E characteristically produce an acute syndrome, there are
reports of chronic infection with hepatitis E among im-
munosu p pr es sed people [14-16].
Hepatitis E is increasingly recognised as a common
infection. In China, seroprevalence rates are above 40%
[17]. In north India, hepatitis E seroprevalence in chil-
dren was 28% [18]. In the UK, 16% of blood donors in
Bristol have serological ev idence of exposure to hepatitis
E with an increased frequency in older men [10].
In 2005 a study of 329 cases of h epatitis E rep orted by
the HPA found 33 who definitely acquired their infection
in the UK and a further 67 who probably did, roughly
one-third of the total [19]. Travellers are usually infected
with genotypes 1 and 2, whereas infections acquired in
this country are usually genotypes 3 or 4. In this study,
none of the patients for who travel data were available
acquired hepatitis E in the UK. This contrasts to at least
7/21 (33%) of the patients with hepatitis A. This may
reflect a sampling bias; symptomatic travellers tend to
present to HTD from a catchment area that is predomi-
nantly urban and who are likely to have little contact
with animals.
Patients who were admitted with hepatitis E had a
longer hospital stay. This may reflect a delay in diagnosis
compared to hepatitis A. Once a diagnosis of hepatitis A
has been confirmed, clinicians are often prepared to dis-
charge the patient.
Previous infection with hepatitis E appears to confer
life-long immunity and a vaccine may soon be widely
available. The Walter Reed Army Research Institute re-
cently published the results of a phase 2 study with a
recombinant protein vaccine candidate that showed
95.5% protection [6], while a phase 3 study of a vaccine
produced in China showed 100% efficacy [7]. However,
until such time, public health measures including hand
hygiene and clean food and water will continue be the
primary means of controlling the spread of hepatitis E.
Copyright © 2013 SciRes. OPEN ACCESS
C. Cosgrove et al. / World Journal of Cardiovascular Diseases 3 (2013) 519-522
Copyright © 2013 SciRes.
In recent years hepatitis E has been seen with increasing
frequency at this hospital and it is now more common
than hepatitis A. It is most often seen among travellers of
Asian descent who go to the ISC to v isit family. Whereas
previous studies have highlighted the frequency with
which pregnant women acquire the infection, this was
not the case in this cohort. Physicians shou ld be aware of
the increasing morbidity associated with this emerging
infectious disease.
We are grateful to all staff at the Hospital for Tropical Diseases. Mar-
garet Armstrong is supported by the Special Trustees of the Hospital
for Tropical Diseases.
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