World Journal of AIDS, 2013, 3, 216-220
http://dx.doi.org/10.4236/wja.2013.33029 Published Online September 2013 (http://www.scirp.org/journal/wja)
Hepatitis E Virus Infection in HIV Positive ART Naïve and
Experienced Individuals in Nigeria*
Georgina N. Odaibo#, David O. Olaleye
Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
Email: #foreodaibo@hotmail.com
Received June 13th, 2013; revised June 30th, 2013; accepted July 10th, 2013
Copyright © 2013 Georgina N. Odaibo, David O. Olaleye. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
ABSTRACT
Background: Studies have shown Hepatitis E Virus to be a causative agent of acute and chronic hepatitis in severely
immunocompromised patients such as organ transplant recipients and person with HIV infection. This study was de-
signed to determine the burden of HEV infection among HIV positive individuals in Nigeria and the effect of HIV
treatment on the burden of HEV infection among this group of patients. Methods: Aliquot of plasma samples collected
for laboratory investigations such as CD4 enumeration, blood chemistry (AST, ALT, Creatine, Urea) were used to de-
termine the presence of HEV IgG and IgM antibodies using commercially available ELISA. Samples analysed in the
study were collected from 180 HIV positive individuals (90 ART naïve and 90 ART experienced) attending the ART
clinic at the University College Hospital, Ibadan, Nigeria. Results: Twenty two of the 180 (12.2%) samples were posi-
tive for either HEV IgG (20/180) or IgM (2/180). The rate of HEV IgG was higher among ART naïve individuals and
the two IgM positive persons were ART naïve. There was no significant difference in the mean CD4 count and mean
ALT between HEV seronegative and seropositive individuals (P = 0.8 and 0.2 respectively). Conclusions: The results
of this study suggest the need to test for HEV infection in HIV positive individuals for the early diagnosis and proper
management since HEV is known to be fulminant in the presence of underlying liver disease that is common among
HIV infected persons. In addition, the use of ART may reduce the incidence of HEV infection in HIV positive persons.
Keywords: HEV Infection; HIV Positive; ART; Nigeria
1. Background
Viral hepatitis is a major cause of morbidity and mortal-
ity globally. Various viral agents including Hepatitis A,
B, C, D, E and G are known as causes of liver diseases
such as cirrhosis, hepatocellular carcinoma and liver fail-
ure [1]. Hepatitis E disease is a self-limited feco-orally
transmitted acute viral infection that occurs most fre-
quently in epidemic forms [2]. The aetiology of the dis-
ease is Hepatitis E Virus (HEV), a non-enveloped RNA
virus belonging to the genus hepevirus of the family He-
peviridae. The virus is transmitted from person to person
feco-orally, hence its transmission is highly associated
with poor hygiene or sanitation [2-4]. The virus has also
been found in animals such as pigs, rodents, deer, and the
possibility of zoonotic transmission of the virus has been
suggested [5-8].
The prevalence of HEV in human population varies
from one geographic location to another with high mor-
tality rates in some areas, especially among pregnant wo-
men and persons with immunodeficiencies including or-
gan transplant recipients [9-12]. The reported prevalence
of HEV infection reported from the USA and Western Eu-
rope ranges from one to five percent [13-15], while the
rate in developing countries ranges from 10% to 100% in
some population groups [16,17]. Labrique and colleagues
[18] in a study in Bangladesh reported a prevalence of
22.5% and the rate in Egypt has been reported to be as
high as 100% among some population groups [16]. Ola
et al. [19] found a seroprevalence rate of 44% among
Health Workers in Nigeria.
*Competing interest: We declare that we have no conflicting interest in
the conduct of the study.
Authors’ contribution: GNO and DOO conceived the idea of the study,
GNO, DOO were involved in the collection and analysis of data, GNO
supervised the laboratory investigations. GNO wrote the draft manu-
script while both authors reviewed the final manuscript and approved
the final version. DOO is the guarantor of the paper.
#Corres
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author.
Copyright © 2013 SciRes. WJA
Hepatitis E Virus Infection in HIV Positive ART Naïve and Experienced Individuals in Nigeria 217
2. Objectives of the Study
Recent studies have shown Hepatitis E Virus to be causa-
tive agent of acute and chronic hepatitis in severely im-
munocompromised patients such organ transplant reci-
pients and persons with HIV infection [9,12]. This study
was designed to determine the burden of HEV infection
among HIV positive individuals in Nigeria and the effect
of HIV treatment on the infection.
3. Study Design
3.1. Study Population
The study participants included 90 HIV positive antiret-
roviral drug naïve and 90 HIV positive ART experienced
individuals attending the ARV treatment clinic at the
University College Hospital, Ibadan, Nigeria for HIV/
AIDS care and treatment. Only individuals who have
been on ART for a minimum of one year were included
among the ART experienced group. Ethical approval was
obtained from the UI/UCH Ethical Review committee for
the study.
3.2. Laboratory Analysis
Aliquot of plasma samples collected for laboratory inves-
tigations such as CD4 enumeration, blood chemistry
(AST, ALT, Creatine, Urea.) were used to determine the
presence of HEV IgG and IgM antibodies using commer-
cially available Enzyme Immunoassay.
3.3. Detection of HEV IgG
The DIA. PRO HEV AB, a 3rd generation EIA by Diag-
nostic Bioprobes (Milano, Italy) was used to test for the
presence of HEV IgG. The assay was carried out accord-
ing to manufacturer’s recommendation. Briefly, 200 ul of
diluted sample (1:20) was added to respective wells coat-
ed with HEV specific antigens. After incubation at 37˚C
for 45 mins, wells of the reaction plates were washed and
conjugate was added. Each reaction plate was washed again
after incubation at 37, chromogen/substrate was then
added and the OD value determined at 450 nm wave-
length. The cut-off value was calculated and results inter-
preted as recommended by manufacturer.
3.4. Detection of HEV IgM
The HEV-IgM ELISA by Wantai Diagnostics, Beijing,
China was used to detect the presence of HEV IgM in the
plasma samples. The 96 wells polystyrene microwell is
precoated with anti-human IgM. On addition of sample,
bound HEV IgM was detected by use of recombinant
HEV ORF2 antigen conjugated to the enzyme horseradish
peroxidase. The assay procedure was carried out as rec-
ommended by the manufacturer. After addition of the
stop solution, absorbance value for each of the wells was
read at a dual wavelength of 450/630 nm.
4. Results
The characteristics of the study population are shown in
Table 1. Two-third of the patients attending the ART cli-
nic during the period of sample collection were female.
The mean age, mean CD4 and mean ALT of the partici-
pants were 39.4 years (range: 17 - 84), 351 cells/ul (range:
16 - 1565) and 27.0 (range: 4 - 212) respectively.
Overall, the rate of HEV infection (combined IgG and
IgM) found in this study is 12.2% (22/180). Twenty of
the 180 (11.1%) patients were positive for HEV IgG while
2 (1.7%) were positive for IgM (Table 2). The preva-
lence of HEV IgG was higher among ART drug naïve
(13.3%) patients while the two individuals who were
Table 1. Demographic characteristics and some laboratory parameters of HIV positive patients tested for HEV infection.
Gender
ART status Mean age (years)
[Range] {SD} Male Female
Mean CD4 (cells/ul)
[Range] {SD}
Mean ALT (IU/L)
[Range] {SD}
Average period on ART
(years) [Range]
ART naïve 37 [17 - 64] {11.2} 28 62 259 [16 - 1022] {221.1}29.3 [1 - 132] {25.9} Not applicable
ART exposed 42 [26 - 84] {10.1} 32 58 443 [26 - 1565] {343.6}24.8 [4 - 212] {36.7} 2 (1 - 5 years)
Overall 39.4 (17 - 84) {10.9} 60 120 351 (16 - 1565) {302} 27.0 (1 - 212) {28}
Table 2. Prevalence of HEV IgG and IgM antibodies by ART statusamong HIV positive patients attending ART clinic at
UCH, Ibadan, Nigeria.
ART status No tested HEV IgG No (%) positiveHEV IgM No (%) positivePast and present HEV infection No (%) positive
ART naive 90 12 (13.3) 2 (2.2) 14 (15.6)
ART exposed 90 8 (8.9) 0 (00) 8 (8.9)
Total 180 20 (11.1) 2 (1.7) 22 (12.2)
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Hepatitis E Virus Infection in HIV Positive ART Naïve and Experienced Individuals in Nigeria
218
positive for HEV IgM were also ART drug naïve with
mean CD4 of 205 and mean ALT of 31. The prevalence
of the infection was higher among female and those in
the 60 years age group followed by the 30 - 39 years
age group (Table 3). The mean CD4 count among ART
experienced individuals was higher than that of ART
naïve (P = 0.004). However, there was no significant dif-
ference in the mean CD4 count among HEV negative
HEV positive individuals (P = 0.1). Overall, the mean
ALT (IU/L) was lower among the HEV positive than
HEV negative ART Naïve (18.4 vs 31.4; P = 0.2) and
ART experienced (20 vs 25; P = 0.7) individuals.
5. Discussion
Hepatitis E virus infection recently has been described as
an emerging infection among patients with immunosup-
pressing conditions of such human immunodeficiency in-
fection [9,20,21]. In this study we found a high rate
(12.5%) of HEV among HIV positive individuals attend-
ing an ART clinic in Nigeria. Although this rate is higher
than the previously reported among similar populations
in the industrialized countries [9,15,22,23], it is lower
than the rates of HEV infection reported among some
population groups HEV endemic areas of Africa [17] and
Asia [10,18]. Interestingly, the prevalence of HEV infec-
tion found in this study is lower than the previously re-
ported rate of 44% among Health workers in Nigeria [19].
Although the reason for this difference is not clear, it has
been suggested that “health care setting is a home for
transmission of infection especially where running water
and other materials for hand hygiene are lacking” [19,24].
Nosocomial transmission of HEV infection has also been
reported [25].
While some studies have shown that HIV infected in-
dividuals are not at higher risk of acquiring HEV infec-
tion than the general population [25], they are at higher
risk of developing chronic HEV infection [15]. The pre-
valence of HEV infection in the general population in Ni-
geria has not been determined, however, the results of
this study suggest the need to test for HEV infection in
HIV positive individuals for the early diagnosis and pro-
per management since HEV is known to be fulminant in
the presence of underlying liver diseases that are com-
mon among HIV infected persons.
The participants in this study includes those who are
on ART (ART experienced) as well as those who are yet
to commence ART (ART Naïve). The rate of HEV IgG
which is indicative of past HEV infection was higher
among the ART naïve group. In addition, the two indi-
viduals who were positive for HEV IgM, an indication of
recent infection was also ART Naïve individuals. This
finding suggests that the use of ART may protect against
acquisition of HEV infection among HIV positive indi-
viduals, probably by improving the immunity of the in-
dividual (as evident in the higher mean CD4 of the ART
experienced individuals). Carry et al. [26] and Keane et
al. [27] have also suggested that the use of highly active
antiretroviral therapy may avert chronic HEV infection.
Study involving larger sample size will be required to es-
tablish this finding.
There was no association of HEV infection with low
CD4 cell count and raised ALT as no significant differ-
ence in the mean CD4 cell count and mean ALT among
HEV positive and HEV negative individuals. This obser-
vation is similar to the finding of Kaba et al. [15] who
reported that anti-HEV prevalence did not differ signifi-
cantly according to CD4 count, Cirrhosis, sex, age, mode
of transmission and infection with HBV/HCV. On the
other hand, Adjie et al. [17] showed a strong association
of HEV positivity and high level of ALT among pig han-
dlers in Ghana [17].
What Is Already Known on This Subject
The rate of HEV infection varies by geographical location and
between population groups.
Hepatitis E Virus is a causative agent of acute and chronic
hepatitis in severely immunocompromised patients such as organ
transplant recipients and persons with HIV infection [9,12].
What This Study Adds to Literature
High burden of HEV infection among HIV positive individuals
in Nigeria.
ART may reduce the chance of acquiring HEV infection as
evidence of recent infection found only among ART Naïve
individuals.
The results of this study suggest the need to test for HEV
infection in HIV positive individuals for the early diagnosis and
proper management since HEV is known to be fulminant in the
presence of underlying liver diseases that are common among
HIV.
6. Acknowledgements
The ART program at the University College Hospital is
supported by USG PEPFAR program through a Coop-
erative Agreement (No: 1U2GPS001058) from the Cen-
ters for Disease Control and Prevention. Funds for anti-
HEV reagents were provided by the HIV/HEPATITIS
project of the Department of Virology (7/225/18). The
content of this article is solely the responsibility of the
authors and does not necessarily represent the official
views of the Centers for Disease Control and Prevention.
We are grateful to all the staffs of the ART clinic and Vi-
rology laboratory for the patient enrollment and labora-
tory analysis. We thank immensely our patients who par-
ticipated in the study.
7. Ethical Considerations
Approval for the study was obtained from the University
Copyright © 2013 SciRes. WJA
Hepatitis E Virus Infection in HIV Positive ART Naïve and Experienced Individuals in Nigeria 219
Table 3. Pattern of HEV infection by age and gender among patients attending ART clinic at UCH, Ibadan Nigeria.
Male Female Total
Age
No tested No (%) Pos No tested No (%) Pos No tested No (%) Pos
<20 2 0 4 0 6 0
20 - 29 8 0 14 2 (14.3) 22 2 (9.1)
30 - 39 18 2 (11.1) 54 9 (16.7) 72 11 (15.3)
40 - 49 20 1 (5) 30 4 (13.3) 50 5 (10.0)
50 - 59 10 0 12 2 (16.7) 22 2 (9.1)
60 8 2 (25.0) 0 0 8 2 (25.0)
66 5 (7.6) 114 17 (14.9) 180 22 (12.2)
of Ibadan/University College hospital ethical review
board. Informed consent was obtained from all partici-
pants in the study.
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