Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis
B co-infected patients attending an urban HIV clinic in Uganda.
Elizabeth Katwesigye¹, Emmanuel Seremba², Fred Semitala¹, Ponsiano Ocama¹
1. Department of Medicine, Mulago Hospital and Makerere University College of
Health Sciences, Kampala, Uganda
2. Department of Medicine, Mulago Hospital, Kampala, Uganda
Abstract
Background: Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeciency virus
(HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and
other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors
associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda.
Methods: We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic
regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver brosis (as de-
termined by the Aspartate transaminase to platelet ratio index and transient elastography) were included.
Results: Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440
cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC
containing regimen). Median duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2% (95% CI
1.14-6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis.
Conclusions: The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban
cohort.
Keywords: Co-infection in Uganda, hepatitis delta antibodies, hepatitis B virus, HIV.
DOI: http://dx.doi.org/10.4314/ahs.v16i4.26
Cite as: Katwesigye E, Seremba E, Semitala F, Ocama P. Low Sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected pa-
tients attending an urban HIV clinic in Uganda. Afri Health Sci. 2016;16(4): 1089-1093. http://dx.doi.org/10.4314/ahs.v16i4.26
Introduction
Hepatitis delta virus (HDV) is a defective virus and de-
pends on the hepatitis B surface antigen (HBsAg) for
its existence
1-3
. Worldwide approximately 15-20 million
people have been exposed to HDV infection, which ap-
proximately represents 5% of the population of chron-
ic hepatitis B.. Hepatitis D virus infection results in the
most aggressive form of chronic viral hepatitis especially
in HIV infected persons
4,5
. Triple infection with HDV/
HBV and human immune deciency virus (HIV) is
common due to shared modes of transmission; mainly
through unprotected sexual intercourse and exposure to
contaminated blood products
6,7
. Current treatment op-
tions for HIV/HBV have a limited effect on HDV in-
fection therefore not be adequate if there is HDV co-
infection as response to HDV will not be achieved and
liver disease progression continues to occur
8-12
. There is
scarcity of data on HDV in Uganda. To the best of our
knowledge there has only been one study which report-
ed HDV antibody prevalence of 30.6 % in the HBsAg
positive population and 3.1 % in the general population
in the Northern part of Uganda
13
. The aim of this study
was to measure the prevalence and to ascertain the fac-
tors associated with hepatitis D antibodies among HIV/
HBV co-infected adults individuals in Uganda.
Methods
This cross sectional study was performed at the Infec-
tious Diseases Institute clinic (IDI), Makerere University,
Uganda located within Mulago Hospital complex. Ever
since it was opened in 2002, this clinic has registered over
10,000 individuals of whom 8,300 are active and are re-
ceiving ART. Over the last two years, routine screening
Corresponding author:
Elizabeth Katwesigye,
Department of Medicine,
Makerere University College of Health Sciences
P.O. Box 7072, Kampala Uganda
Tele: +256782770647
Email: katwesigyee@gmail.com
African Health Sciences Vol 16 Issue 4, December, 2016
1089
of HIV-infected clients for hepatitis B virus has been
ongoing and there 250 HIV/HBV co-infected patients
attending the IDI clinic.
Between September 2015 and February 2016, we were
able to recruit 189 participants. Those that provided writ-
ten informed consent had their CD4 T-cell count, clinical
history relevant to HIV and HBV diagnosis and medi-
cation use focusing on ART abstracted from the clinic
records. This information was supplemented by a data
collection tool that captured socio demographic charac-
teristics and risk factors of HDV transmission. Partic-
ipants had a physical examination focusing on liver dis-
ease and a complete blood count and liver enzyme assays
done. In addition, all the participants underwent liver
brosis assessment using non-invasive approaches; the
Aspartate transaminase to platelet ratio index (APRI) and
transient elastography with the aim of comparing liver
disease severity between the HDV and non HDV infect-
ed. We dened liver brosis as an APRI score of ≥ 1.5
and transient elastography score of ≥ 9 kpa. Serum was
tested for HDV IgG antibodies using the HDV IgG ELI-
SA assay kit (AccuDiag™ HDV-IgG ELISA, Diagnostic
automation, inc. Woodland Hills, CA 91367, USA). The
manufacturer reports 100% sensitivity and specicity for
detecting HDV IgG antibodies using this test.
The study obtained ethical approval from Department
of Medicine, School of Medicine Research and Ethics
Committee (SOMREC), Makerere University, College of
Health Sciences and the IDI scientic review committee.
Statistics
Data collected was analyzed using STATA software pack-
age version 11. Logistic regression was performed to de-
termine the factors associated with anti-HDV. A P-value
of < 0.05 was considered to be signicant.
Results
A convenient sample of 189 HIV/HBV co-infected pa-
tients was recruited. The study population was composed
mainly of young individuals; median age of 40 (IQR 33-
46) years and of sound immunological status (median
CD4 440 (IQR 155-590 cells/yl). Ninety-eight percent
were on ART regimens that contained anti-HBV active
medication (95.2% were on TDF/3TC while 4.8% on
3TC containing regimen, 2% were not on ART). Medi-
an duration on ART was 36 months (IQR 22-72). The
majority (56%) had documented HIV infection for more
than 5 years and over two-thirds had been diagnosed with
HBV co-infection at least two years prior to this study
(table 1).
The prevalence of hepatitis delta antibody was 3.2% (95%
Table 1
Baseline characteristics of the HIV/hepatitis B co-infected patients at IDI clinic,
Uganda, (N=189).
Characteristic
N=189 (%)
Gender
Female
80 (42.3%)
Male
109 (57.7%)
Median age (IQR) years
40(IQR 33-46)
Age categories
20-30
37 (19.7%)
31-45
103 (54.8%)
45+
ON ART
Yes
No
48 (25.5%)
186(98.4%)
3(1.6%)
ART regimen
TDF/3TC
95.2%
3TC
Median duration on ART (IQR)months
4.8%
36 (22-72)
Median baseline CD4 count (IQR), cells/µl
Median current CD4 count (IQR),
cells/µl*
155(46-328)
440(155-590)
Median current viral load (IQR) ,copies/ml)**
20 (20-75)
Time since HIV diagnosis
≤5 years
82(43.8%)
>5 years
105(56.2%)
Time since HBV diagnosis
≤1 years
73(39%)
≥1 years
114(61%)
*Current CD4 results was available for 188 patients
** Current HIV viral load was available for 174 patients
African Health Sciences Vol 16 Issue 4, December, 2016
1090
condence interval 1.42-6.92%). All the participants that
tested positive for hepatitis delta antibodies were male.
They had been diagnosed with HIV and started on ART
at least ve years prior to this study (table 2).
The liver enzyme levels (ALT,AST), and the platelet
count did not signicantly differ among the individuals
with positive or negative for anti-HDV, neither was there
a difference in the HIV viral load and CD4 T-cell count
among individuals in these categories.
Furthermore, there was no evidence of liver brosis
among the individuals that tested positive for anti HDV
antibody (normal APRI SCORE (< 1), and 5/6 had a
transient elastography score of <7 kpa). One of the par-
ticipants had invalid broscan test. Among the HDV
negative participants, liver brosis was present in 5 % by
the APRI score and 20 % by transient elastography score.
Discussion
Our study demonstrated a prevalence of hepatitis delta
antibodies in HIV/HBV co infected patients in an urban
HIV clinic in Uganda of 3.2%. These results are compa-
rable to some other studies in sub-Saharan Africa (SSA)
done in similar settings
14-16
but quite different in other se-
lected sub-populations including those with chronic liver
disease in West Africa where a high anti-HDV prevalence
ranging from 12.2 to 81.7% was documented
17
. Also oth-
er studies in Africa have showed varying prevalence rates
of HDV ranging from 0-50% in different countries
18-20
.
Similarly in the developed countries, high anti-HDV
prevalence’s of 10-15% have been documented in recent
studies
1,21,22
. Reasons for the variations in the prevalence
of HDV exposure or infection are not clear. This could
be a result of modes of transmission whereby in some
of these countries there could be higher rates of IVD
use
21,22
.
In addition, we have conrmed earlier ndings that male
gender was signicantly associated with anti HDV anti-
body positivity
23,24
.
Within the limits of small numbers in our study, we ob-
served that living with HIV for ve or more years was
also signicantly associated with HDV antibodies despite
anti retro viral (ART) use. This data may suggest that
ART may not affect HDV antibodies however a larger
study is required to assess the impact of ART on HDV
infection
8
. However, HIV may increase the risk of HDV
acquisition since immunosuppressive states increase the
likelihood of chronic hepatitis B which serves as a buffer
to hepatitis D acquisition.
This study did not demonstrate signicant differences
in the liver brosis scores among the HDV negative and
positive patients, which is in agreement with the clinical
and laboratory data that did not suggest that individu-
als with detectable anti-HDV had a chronic liver disease.
However, it may also be possible that the results reect
false positive test for HDV since no conrmation was
made using HDV viral loads. On the other had it could
also be a result of resolved infection. These have been
demonstrated in others studies as well in African set-
tings
14
.
Limitations
Our study has some limitations. We used a convenient
sample of HIV/HBV co-infected individuals that we
could access. The few numbers of anti HDV antibody
positive individuals identied in this study limited our
ability to ascertain the factors associated with triple in-
fection. However, given that similar ndings had been
recorded elsewhere in East Africa, our ndings are like-
ly to be valid. Furthermore, we were unable to perform
HDV RNA to conrm current hepatitis delta infection
and hence this study was based on HDV exposure and
not necessarily current infection.
Conclusion
The sero prevalence of HDV antibodies among the HIV/
HBV co-infected patients is very low in a Ugandan ur-
ban cohort as compared with developed countries where
intravenous drug use is common. Routine screening for
anti-HDV among individuals with HIV/HBV co-infec-
tion in this setting may not be cost effective, however
in absence of a known etiology, targeted testing can be
done for patients with liver disease if not improving or
developing liver disease while on a tenofovir based-ART
regimen.
Following this pilot, a larger study in which HDV-RNA
testing is performed is recommended to assess with bet-
ter accuracy the magnitude of HDV infection in Uganda.
Acknowledgements
The authors would like to acknowledge the Infectious
Diseases Institute clinic staff and patients for the partic-
ipation in this study. We also acknowledge the nancial
contribution provided by Forgarty International scholar-
ship program which made this study possible though they
African Health Sciences Vol 16 Issue 4, December, 2016
1091
did not participate in the conception, data collection or
analysis in this study.
Conict of interest
The authors declare no conict of interest
Author’s contributions
EK, ES, FS and PO participated in the conception of the
study, ES, FS and PO assisted in editing of the proposal.
EK collected all the data and drafted the manuscript. ES,
FS and PO helped with review of the manuscript. All
authors approved the nal manuscript
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