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Contents lists available at ScienceDirect

Journal of Clinical Virology

journal homepage: www.elsevier.com/locate/jcv

Case Report

Hepatitis A related acute liver failure by consumption of

contaminated food
Heng Chi a , Elizabeth B. Haagsma b , Annelies Riezebos-Brilman c , Arie P. van den Berg b ,
Herold J. Metselaar a , Robert J. de Knegt a,
a

Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
c
Departments of Medical Microbiology, Division of Clinical Virology, University Medical Center Groningen, Groningen, The Netherlands
b

a r t i c l e

i n f o

Article history:
Received 10 May 2014
Received in revised form 14 August 2014
Accepted 19 August 2014
Keywords:
Acute viral hepatitis
Foodborne
Outbreak
Lycopersicon esculentum

a b s t r a c t
We present a patient with no medical history admitted for jaundice and dark coloured urine. Further
investigations revealed hepatitis A related acute liver failure while the patient had no travel history,
nor contact with infected individuals. After admission, the patient deteriorated fullling the Kings College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and
recovered. Careful investigation identied imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010
affecting 13 patients. Virus sequence analysis of our patients virus showed a strain commonly found in
Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed
countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review
the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute
liver failure, and hepatitis A vaccine.
2014 Elsevier B.V. All rights reserved.

1. Why this case is important

The hepatitis A virus (HAV) is a RNA virus transmitted via the
faecaloral route and is the most common cause of acute viral hepatitis in the world. Typically, patients present with non-specic
symptoms such as fever, malaise, nausea, vomiting and u-like
symptoms accompanied with dark urine and jaundice [1]. Hepatitis A is a self-limiting disease, but is accountable for an estimated
3.1% of acute liver failures [2].
The incidence of HAV infections is low in developed regions
(Western Europe, and North America). Infections are predominantly associated with person-to-person contact with an infected
person or travel to high endemic regions (sub-Saharan Africa, and
parts of South Asia) [3]. In the last decade, however, hepatitis
A outbreaks are emerging in developed countries, mostly caused
by imported food contaminated with the HAV. This emergence
can be largely attributed to the vast and increasing trade of food

Corresponding author at: Department of Gastroenterology and Hepatology,

Erasmus MC, University Medical Center Rotterdam s-Gravendijkwal 230, Room Ha203, 3015 CE, Rotterdam, The Netherlands. Tel.: +31 10 703 5942;
fax: +31 10 436 5916.
E-mail address: r.deknegt@erasmusmc.nl (R.J. de Knegt).

products globally. In this case report, we describe a case of hepatitis A related acute liver failure caused by contaminated food and
review the literature on this topic.

2. Case report
A 39-year old man with no medical history was admitted to the
Erasmus MC University Medical Centre Rotterdam (Rotterdam, The
Netherlands) in January 2010. His symptoms started one week earlier with malaise, nausea, and vomiting. Since two days, he noted
jaundice and dark coloured urine. He did not have fever, and had
not travelled for several months. Nobody in his surroundings was
sick. We did physical examination on admission, and found a disorientated man with jaundice and apping tremor suggesting acute
liver failure accompanied with hepatic encephalopathy.
Laboratory results revealed aspartate transaminase 2465 U/L
(<34 U/L), alanine aminotransferase 6555 U/L (<44 U/L), bilirubin
209 mol/L (<16 mol/L), prothrombin time 79 s, activated partial thromboplastin time 55 s, international normalised ratio 6.6,
factor V 0.10 IU/mL, and creatinine 208 mol/L (65115 mol/L).
Due to the severity of his condition (fullling the Kings College
criteria for acute liver failure), we immediately placed him on the
high-urgency waiting list for liver transplantation and performed

http://dx.doi.org/10.1016/j.jcv.2014.08.014
1386-6532/ 2014 Elsevier B.V. All rights reserved.

Please cite this article in press as: Chi H, et al. Hepatitis A related acute liver failure by consumption of contaminated food. J Clin Virol
(2014), http://dx.doi.org/10.1016/j.jcv.2014.08.014

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a broad range of diagnostics. Initial differential diagnosis for acute

liver failure included viral hepatitis (hepatitis A, B, and E), druginduced liver failure (acetaminophen), autoimmune hepatitis, and
Wilsons disease. Liver ultrasonography showed no abnormalities.
As for virological results, the patient was negative for hepatitis B
surface antigen, anti-HBc, anti-hepatitis C virus, IgM and IgG antihepatitis E virus, IgM and IgG cytomegalovirus, and epsteinbarr
virus DNA. However, the test for hepatitis A virus specic IgM and
IgG antibodies was positive, and therefore the diagnosis hepatitis A
related acute liver failure was made. One day after admission he was
transferred to the intensive care unit as his hepatic encephalopathy
worsened and his renal function deteriorated. The following day he
underwent a successful liver transplantation. The patient recovered
and was discharged one month later. The patient is doing well now.
Our patient was part of a hepatitis A outbreak in the Netherlands
in 2010. His infection source was unclear as he did not travel in
the past months, nor did he have contact with infected individuals. A similar case occurred in the same period in the north of
the Netherlands. A 59-year old man was admitted to the University
Medical Centre Groningen (Groningen, the Netherlands) with also a
hepatitis A related acute liver failure. This patient had neither travel
history, nor contact with infected individuals in the past months.
He underwent liver transplantation two days after admission and
recovered.
Hepatitis A is a notiable disease in the Netherlands, and
therefore both patients were reported to the national authorities. The National Institute for Public Health and the Environment
(the RIVM) recognised a hepatitis A outbreak affecting 13 geographically spread patients in the Netherlands between December
2009 and February 2010. Sequence analysis showed that all 13
patients were infected with an identical HAV strain (HAV genotype 1B). After careful investigation, evidence suggested imported
semi-dried tomatoes as the source of the outbreak. Upon further
questioning, both our patients reported substantial consumption
of semi-dread tomatoes. In addition, we identied a virus sequence
in both our patients that was commonly found in infected travellers returning from Turkey and hepatitis A patients in Turkey
(Fig. 1).

3. Other similar and contrasting cases in the literature

The transmission of HAV by contaminated food or water is
known phenomenon, but was considered rare in Western countries
[1]. However, a population-based surveillance study from the US
showed that food or waterborne outbreaks were responsible for
approximately 7.2% of reported hepatitis A cases [4]. One of the
largest Western foodborne hepatitis A outbreak affecting at least
601 individuals was reported in the US in 2003 [5]. In this outbreak, contaminated green onions from Mexico were identied as
the source, and were responsible for 3 deaths and at least 124 hospitalizations. The rst hepatitis A outbreak by semi-dried tomatoes
was reported in Australia in 2009 [6]. This foodborne outbreak led
to 562 reported hepatitis A cases which was a 2-fold increase of
the average annual hepatitis A cases. Furthermore, HAV RNA was
detected in samples of imported semi-dried tomatoes. In the following years, semi-dried tomatoes were responsible for multiple
foodborne outbreaks: twice in the Netherlands (2010 and 2011)
[7,8], France (2010) [9], and the United Kingdom (2011) [10]. In
the French outbreak, 59 cases were identied, whereof 28 were
hospitalized. Recently, frozen berries were identied as the culprit for hepatitis A outbreaks in Nordic countries and Italy [11,12].
Denmark, Finland, Norway, and Sweden reported 103 cases of hepatitis A between October 2012 and June 2013.

Fig. 1. Phylogenetic tree of hepatitis A virus sequences of both patients and reference strains. Phylogenetic analysis of HAV sequences of both patients (patient A
and B) in relation to samples of other patients in Groningen (GenBank accession
number-NL-Gro-year.nr) and reference strains (Gen Bank accession numbers) of
HAV genotype 1A, 1B, 2 and 3. Patient A: 39-year-old man. Patient B: 59-year-old
man. For phylogenetic analysis a fragment of 410 bp of VP1-2A were aligned with
Clustal W 2.0 and phylogenetic trees were constructed by the neighbour-joining
method with bootstrap 1000 using MEGA 4.0 using different reference strains of HAV
from GenBank. The HAV sequences derived from this work are submitted to GenBank
(accession numbers KM261582-KM261590). *Men who have sex with men.

4. Discussion
The impact of these emerging foodborne hepatitis A outbreaks
in developed regions should not be underestimated. The Australian outbreak resulted in at least 200 additional hepatitis A cases
and was despite public health intervention an ongoing problem.
Furthermore, the outbreaks were responsible for many hospitalizations, several liver transplantations and even deaths. Importantly,
the risk on acute liver failure and mortality increases with advancing age or the presence of chronic liver disease (chronic hepatitis
B or C) [1315]. The prognosis after the development of acute liver
failure is poor with 45% of patients transplanted or dead [2]. Moreover, due to the declining incidence of hepatitis A in developed
countries, a small proportion of the population had experienced a
HAV infection during childhood resulting in a large proportion of
susceptible adults [3]. Not only is the chance on fulminant course
and mortality lower in children compared to adults, but the clinical
manifestation of HAV infections is also usually mild and subclinical in children. Nonetheless, the incidence of acute liver failure
after HAV infection is rare. In a Greek study, among 286 patients
admitted for hepatitis A, 0.35% of the patients developed acute liver
failure [16].
As there is an effective hepatitis A vaccine, these emerging outbreaks raise the question even more whether a universal hepatitis
A vaccination programme is needed in developed countries. Vaccination programmes targeting high-risk individuals are already in
place in several developed countries [17]. However, the effectiveness of such targeted vaccination programme has been challenged
as hepatitis A outbreaks are not limited to high-risk individuals
[18]. From an economic perspective, a universal hepatitis A vaccination programme in a developed country may be more effective
and cost saving [17,19]. In 2005, the US recommended to vaccinate all children aged 1223 months against hepatitis A above
its targeted vaccination [20]. The cost-effectiveness of vaccination
depends on the age-specic prevalence and severity of the targeted
disease [21]. For each developed country, these factors may vary,
but emerging outbreaks should be taken into consideration.

Please cite this article in press as: Chi H, et al. Hepatitis A related acute liver failure by consumption of contaminated food. J Clin Virol
(2014), http://dx.doi.org/10.1016/j.jcv.2014.08.014

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Given the vast volume of imported food and large proportion

of susceptible adults in developed countries, foodborne hepatitis A outbreaks are a considerable concern. The benet of a
universal vaccination programme should be assessed by national
health authorities of developed countries. The impact of foodborne hepatitis A outbreaks should not be underestimated due
to the association of increased severity with advancing age. Both
our patients needed liver transplantation after developing hepatitis A related acute liver failure after consumption of contaminated
food. Acute liver failure following hepatitis A is uncommon, but its
prognosis is poor.
Funding
None received.
Competing interests
None declared.
Ethical approval
Not required.
Patient consent
Obtained.
Author contributions
Heng Chi: drafting of the article, and nalising the article. Els
Haagsma: patient care, drafting of the article, and nalising the
article. Annelies Riezebos-Brilman: drafting of the article, virus
sequence analysis, drafting of the article, and nalising the article. Arie van den Berg: patient care, and nalising the article.
Herold Metselaar: patient care, and nalising the article. Robert
de Knegt: patient care, drafting of the article, and nalising the
article.
Acknowledgement
The authors would like to thank Harry Vennema for his contributions to the virus sequence analysis.

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Please cite this article in press as: Chi H, et al. Hepatitis A related acute liver failure by consumption of contaminated food. J Clin Virol
(2014), http://dx.doi.org/10.1016/j.jcv.2014.08.014