Hepatitis E is more common than hepatitis A among returning travellers presenting to tertiary care

doi:10.4236/wjcd.2013.38082

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World Journal of Cardiovascular Diseases, 2013, 3, 519-522 WJCD

http://dx.doi.org/10.4236/wjcd.2013.38082 Published Online November 2013 (http://www.scirp.org/journal/wjcd/)

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

Email: [email protected]

Received 15 August 2013; revised 25 September 2013; accepted 4 October 2013

cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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

1. INTRODUCTION

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.

2. METHODS

All patients seen at the HTD between August 2000 and

OPEN ACCESS

C. Cosgrove et al. / World Journal of Cardiovascular Diseases 3 (2013) 519-522

520

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

three.

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.

3. DISCUSSION

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

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.

Bangladesh

35%

India

39%

Pakistan

10%

All over SE Asia

Afganistan

Latin America

3% Sudan

(a)

Sri Lanka

India

21%

Pakistan

Africa

21%

Madagascar

Latin America

No Travel

38%

(b)

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.

C. Cosgrove et al. / World Journal of Cardiovascular Diseases 3 (2013) 519-522

522

4. CONCLUSION

OPEN ACCESS

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.

5. ACKNOWLEDGEMENTS

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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