Hepatitis E Virus Infection in HIV Positive ART Naive and Experienced Individuals in Nigeria

doi:10.4236/wja.2013.33029

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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: #[email protected]

Received June 13th, 2013; revised June 30th, 2013; accepted July 10th, 2013

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

ondin

author.

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)

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

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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