Sero-prevalence and factors associated with Hepatitis B and C co-infection in
pregnant Nigerian women living with HIV Infection
Oliver Chukwujekwu Ezechi1, &, Olufunto Olufela Kalejaiye1, Chidinma
Vivian Gab-Okafor1, David Ayola Oladele1, Bamidele Oludare
Oke1, Zaidat Adesola Musa1, Sabdat Ozichu Ekama1, Harry
Ohwodo1, Endurance Agahowa1, Titilola Gbajabiamilla1, Paschal
Mbanefo Ezeobi1, Azuka Okwuraiwe2, Rosemary Ajuma Audu
R2, Rosemary Nwakaego Okoye3, Agatha Nkiru David1, Nkiruka
Nonyelum Odunukwe1, Dan Ifeanyi Onwujekwe1, Innocent
1Clinical Sciences Division, Nigerian Institute of Medical Research,
Yaba Lagos Nigeria, 2Human Virology Laboratory, Nigerian Institute
of Medical Research, Yaba Lagos Nigeria, 3HIV Counseling and Testing
Centre, Nigerian Institute of Medical Research, Yaba Lagos Nigeria
Dr. Oliver Ezechi, Clinical Sciences Division, Nigerian Institute of Medical
Research, Yaba Lagos Nigeria
Perinatal and horizontal transmission of Hepatitis B occur in areas of high endemicity
as most infections are acquired in the first 5 years of life. Unless Hepatitis
B and C infected pregnant women identified, and appropriate treatment provided,
children born to these women are at high risk of chronic Hepatitis B (and C)
virus infection. The objecive of this study was to determined the prevalence
Hepatitis B and C Virus infection in pregnant HIV positive Nigerians.
A cross sectional study among HIV Positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women were screened for Hepatitis B and C Virus infection at enrollment. HIV viral load, CD4 count, liver transaminases and hemoglobin levels were also determined. Data were managed with SPSS for windows version. Ethical approval was obtained from the Institution?s Ethical Review Board.
Of the 2391 studied subjects, 101(4.2%) and 37(1.5%) respectively were seropositive
for Hepatitis B and C Virus infection. Twowomen (0. 08%) had triple infections.
blood transfusion, (cOR: 2.3; 95% CI:1.1 - 4.6), history of induced abortion
(cOR:2. 2;95% CI:1.3 - 3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2.
2;4.2) were significantly associated with HBV. History of induced abortion was
the only factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9).
Hepatitis B Virus infection (4.2%) is relatively common in our environment and
associated with induced abortion, blood transfusion and elevated baseline transaminase.
Hepatitis C Virus infection (1.5%) is less common and associated with only history
of induced abortion.
Globally, hepatitis B virus (HBV) infection is most common form of chronic hepatitis
and the leading cause of chronic liver diesase and liver-related deaths [1, 2].
About 350 mllion and 190 million persons are chronically infected with HBV
and Heptatitis CVirus (HCV) respectively and are at high risk of death from
active hepatitis, cirrhosis and primary hepatocellular carcinoma [3, 4].
The prevalence of HBV infection is greatest in the low income countries of sub-Saharan
Africa and South East Asia where 8-10% are chronic carriers and these same regions
habours over two-thirds of the global HIV burden [5-7
the Western world, chronic HBC and HBV co-infection are found in approximately
30% and 10% of HIV-positive personsrespectively, with only 1% being triply infected
with HIV, HBV and HBC [8
Studies across Nigeria have shown varying prevalences of HBV/HIV co-infection
from 9. 2% to as high as 70. 5. % while that of HIV/HCV co-infection ranged between
0. 5% and 14. 7% [9-12
]. HBV and HCV infections occur frequently
among HIV infected patients because of shared routes of transmission. Most HBV
infections have been found to occur within the first 5 years of life in high
endemicity regions of Asia and Africa through perinataland horizontal transmission
and approximately 25% of infected infants will die of HBV related chronic liver
disease in adulthood [13
unless HBV infected pregnant women and associated factors for infection are identified,
and adequate treatment provided, their babies are at high risk of HBV infection
and its complications later in life.
For both hepatitis HBV and HCV, co-infection with HIV is associated with accelerated
progression to cirrhosis and thus a higher mortality. Whether or not HCV directly
impacts HIV disease progression remains controversial [15
Furthermore, individuals co-infected with Hepatitis B and C are risk of hepatoxicity
associated with the use of antiretroviral drugs [13-19
Unfortunately, few studies have addressed co infection of HBV and/or HCV in HIV infected pregnant women more so in Nigeria. This study was conducted to determine the prevalence of and factors associated with HBV and HCV infection among HIV-infected pregnant women in a large HIV treatment centre in southern western Nigerian cosmopolitan city of Lagos.
Study design and Population
The study was a cross-sectional survey conducted at the HIV treatment centre, Nigerian Institute of Medical Research, Lagos. NIMR is the apex medical research Institution in Nigeria charged with the responsibility to conduct research into disease of public health importance in the country. However following the initiation of the Federal Government of Nigeria antiretroviral drug access programme in 2002, it was selected as one of the 25 treatment centres. It was selected principally to provide the research backup for the National HIV programme. Currently the centre provides free comprehensive HIV care, treatment and support for over 19, 000 patients.
Patients are enrolled into the HIV treatment programme following a referral from the HIV Counseling and Testing Centre (HCT), Nigerian Institute of Medical Research Lagos or transfer from other government HIV treatment centres. HIV positive pregnant women on their first visit to the PMTCT clinic between January 2006 and December 2011 who signed an informed consent to participate in the study were recruited for the study. Excluded from the study were women who declined consent to be part of the study, however they were provided PMTCT services.
Patients are enrolled into the HIV treatment programme following an HIV status determination at the HCT centre as stipulated by the Nigerian National HIV counseling and Testing Guidelines. The HIV status of the pregnant women screened positive are further confirmed at the Human Virology Laboratory (HVL) with Western blot. The women found positive were further evaluated for Hepatitis B and C infection, full blood count, blood chemistry, CD4 count and HIV viral load, using standard methods at the HVL. Hepatitis B Virus or Hepatitis C - infection were based on seropositivity to Hepatitis B surface antigen or Hepatitis C antibody respectively.
At enrollment, information about sociodemographic characteristics, likely mode of HIV acquisition, sexual history, history of blood transfusion, obstetric history, medical history and clinical findings were collected in an antenatal initial case record form specifically designed for the programme. The obtained historical, clinical and laboratory information were thereafter entered into an electronic PMTCT data base by trained data entry clerks using file maker pro. Relevant information for this specific analysis were extracted from the PMTCT Data base and exported to SPSS version 19 for analysis. Frequency distributions were generated and univariate analysis using relevant statistics was performed to identify factors associated with HBV and HCV/HIV coinfection. Logistic regression was used to identify independent determinants for HBV and HCV/HIV coinfection in pregnancy while controlling for potential confounders. The variable with the strongest association in the univariate model was estimated first, followed by others in descending other. In the analysis, the comparison group was HIV positive pregnant women without HBV and HCV coinfection. P<0. 05 was considered to be statistically significant.
Approval for the study was obtained from the Institutional Review Board of the
Nigerian Institute of Medical Research, Lagos Nigeria. Written informed consents
were obtained from participants for the use of their data for the study however
women who declined consent
to participate in study were provided care like other women according to Nigerian
National PMTCT and HIV treatment guidelines but excluded from research.
A total number of 2392 HIV positive pregnant women enrolled in the PMTCT programme during the study period were invited to participate in the study. All but one signed a written informed consent to participate in the study. Information of the 2391 women were used for this analysis.
Characteristics of the women in the study:
the sociodemographic, reproductive
and laboratory characteristics of the 2391 HIV positive women studied is shown
. The mean age of the women was 29.5 ± 4.4 years with range 14 - 44
years. Majority of the women were within the age group 20-29 (51.9%). Most of
had at least a previous delivery (71.9%), were married (81.5%), had at least
a secondary education (81.7%) and were gainfully employed (78.1%). The predominant
route of HIV infection was through heterosexual contact (78.5%). The mean gestational
age at enrollment was 23. 7±11.7
years (range 4-41), with majority (85.5%) of the women enrolling after their
Prevalence of and associated factors for HBV co-infection:
of the 2391
women in the study, 101 were found to be Hepatitis B surface antigen positive;
prevalence of 4. 2% (95% CI 3. 05-5. 9%). Prevalence ranged from 3. 3% (95%
CI 2. 1-7. 3%; 14 of 429) for women aged less than 20 years to 4.5% (95% CI
2.4 - 9.1%; 76 of
1687) for women aged between 20-35 years. Table
shows the association between
select maternal characteristics and Hepatitis B co-infection. Although a history
of blood transfusion (cOR:2.3; 95% CI:1.1 - 4.6), history of induced abortion
(cOR:2. 2;95% CI:1.3 - 3.6), viral load greater than 100, 000 copies (cOR:1.
- 3.2) and ALT ≥45
(cOR: 2.2; 95% CI: 2.2 - 4.2) were found to be associated with Hepatitis B co-infection
at univariate analysis. However after adjustment at multivariate analysis while
controlling for possible confounders showed that history of blood transfusion
(aOR: 2.4; 95% C:1.4 - 4.4), induced abortion (aOR: 1.4; 95% CI: 1.4 - 3.1)and
elevated baseline ALT (aOR: 2.5; 95% CI:1.3 - 3.5) retained their independent
with Hepatitis B co-infection.
Prevalence of and associated factors for HCV co-infection:
of the 2391
women in the study, 37 were found to be Hepatitis C antibody positive; HCV antibody
prevalence of 1. 5% (95% CI
1. 23 - 3. 1%). It ranged between 1. 4% (95% CI 1. 1-6. 4%; 32 of 2225) for
women aged between 20 and 35 years and 11. 1% (95% CI 4.5 - 15.1%; 2 of 18)
aged less than 20 years. The association between select maternal characteristics
and Hepatitis C co-infection is shown in Table
. Univariate and multivariate
analysis after controlling for confounders showed that only a history of induced
abortion was found to be associated with Hepatitis C co-infection (aOR:1. 9;95%
CI:1. 3- 3. 9).
Triple infection among the women:
two of the 2391 women in the cohort,
tested positive to both HBV and HCV infection; HCV/HBV prevalence of 0. 08%.
A few studies across Africa have shown a variation in the prevalence of HIV/HBV
co infection in pregnancy. The prevalence of HBV /HIV co-infection in pregnant
women of 4. 2% in our study was similar to 4. 2% by Eke and colleagues in Nnewi,
South East Nigeria and 4. 1% by Pirrillo and colleagues from Rwanda, South
Africa [20, 21]. Landes and colleagues
in the European Collaborative studyalso reported a similar prevalence of 4.9%
. A likely explanation for this is that they found
that HbsAg positivity was associated with black African origin of whom accounted
for one fifth of their study population . Higher prevalence
of 8. 9 and 9. 0% respectively were reported by Adesina et al. from Ibadan
Nigeria and Rouet et al. from Abidjan, Cote d'Ivoire [23, 24].
The differences in social and cultural practices as well as varying sample
test kit sensitivity and specificity may have been responsible and accounted
for the variation in prevalence rates in the Nigerian studies .
However, a lower prevalence of 1. 5% was reported by Santiago-munozet al from
which can be explained by North America being a low endemicity area for Hepatitis
The factors associated with HBV co-infection in our cohort were a history of
blood transfusion, (aOR:2. 4; 95% CI:1.4 - 4.4), induced abortions(aOR:2.
2;95% CI:1.4 - 3.9), and elevated baseline ALT levels (aOR:2. 5; 95% CI:1.3-3.5).
Potential causes for adult transmission for Hepatitis B (and HIV) exist including
transfusion. It is likely that these sources of blood were not screened for
]. The association of HBV/HIV co infection and induced
abortions may be related to the fact that abortion is not legal in Nigeria and
a majority of womenwith unwanted pregnancy patronize quacks who often perform
under unhygienic environment using unsterilized equipment. Also unwanted pregnancy
may be a surrogate for unprotected sexual intercourse which is a known risk factor
for both hepatitis B and HIV infections.
Co-infection with HIV has been found to worsen Hepatitis B (and C) infection
and progression [15
the effect of HBV and
directly on HIV disease progression remains controversial [15
Our study, similar to others, showed no association between HIV disease severity
by CD4 count and HIV viral load with HBV co infection [22
Elevated Transaminase levels were associated with HIV/HBV co-infection in cohort
which was similarly reported by studies from Ibadan [27
A number of causes of elevated liver enzyme transaminases in Hepatitis B infection
have been identified in other studies and include HBeAg seroconversion, acute
infection with hepatitis D and uninhibited HBV viral replication [13
These causes however were not evaluated in our study. Studies from China have
linked ALT levels of at least >0. 5-2 times the upper limit of normal in patients
with Hepatitis B infection with a greater risk of development of complications
of chronic hepatitis [28
]. It may suffice to add that, co-infection
with Hepatitis B increases the risk of hepatotoxicity from antiretroviral therapy
at least 3-5 fold and can pose challenges to treatment modalities [19
Our study did not find an association between maternal age and HIV/HBV co-infection.
This finding differed from studies in Europe and South -Eastern Nigeria where
women aged between 25-29 years and 20-30 years respectively were found to be
at a significant risk of HIV/HBV co- infection [22
The Nigerian researchers attributed this to the higher prevalence of HIV as
as the likelihood of high sexual activity in these age groups [25
The 1. 5% prevalence of HCV/HIV co-infection in this study compares with 1.5%
by Adesina et al from Ibadan, 1. 0% by Rouetet al from Abidjan and 1.3% by
Simporeet al from Ouagadougou, Burkina Faso [23
Higher prevalence of 4. 9% and 12. 3% in Texas, USA, and Europe were reported
al and Landeset al from Europe and was attributed to intravenous drug use in
these populations [22
]. At present
intravenous drug use is not a major challenge in our environment and thus may
have accounted for the lower prevalence.
The only factor found to be associated with HCV/HIV co-infection in our cohort
was a history of induced abortion. (aOR:1. 9;95% CI:1. 3- 3. 9). Hepatitis C appears
to be of a lower prevalence than Hepatitis B in our setting but does share similar
modes of transmission as Hepatitis B and HIV. Maternal age, HIV viral load and
CD4 counts were not associated with HCV/HIV co infection in this study. This
however differed from findings from the European collaborative study in which
maternal age>35years and high HIV viral levels were associated with HCV/HIV co-infection
]. Although, the effect of HBV and HCVinfection on HIV
disease progression remains controversial, it has been suggested that, co-infection
between Hepatitis C virus and HIV may be associated with a rapid decline in the
CD4 count, rapid progression of HIV infection and increased morbidity and mortality
A very small proportion of our cohort(0. 08%) had triple infections of HBV, HCV
and HIV which is similar to findings of 0. 1% at Ibadan suggesting that all 3
co-infections in pregnant women is uncommon in our setting [23
Although our study did try to compare as best as possible with other previous
we did have our limitations. As we
were only able to look at HBsAg positivity and Hepatitis C antibody as markers
for HBV and HCV respectively, and had no information on other serum markers,
we were therefore unable to investigate serological evidence of active or past
infection for either HBV of HCV or prior immunization for HBV.
In view of the relatively high prevalence of 4.2 % for HBV and 1.5% for HCV
in this study, routine screening of all pregnant women for HBV and HCV as well
as prompt referral and treatment to reduce perinatal transmission and thus
chronic hepatitis in children should be adopted as standard of care. However
in rural areas with limited capacity, a high index of suspicion should be entertained
in pregnant women with HIV infection, previous blood transfusion and a history
of induced abortion. This category of women should be referred to facility
with HBV and HCV screening.
The Authors declare no competing interest.
Ezechi OC, Kalejaiye OO, Gab-Okafor CV, Oladele DA:
Conceived and designed the original draft of the study, analysed and interpreted
the generate data, revising the draft manuscript for important intellectual
content and gave approval to the final version. Oke BO, Musa AZ, Ekama SO,
Ohwodo H, Agahowa E: Acquired the data, drafted the first manuscript, collated
contribution of all other authors at every stage and approved the final version
of the manuscript. Gbajabiamilla T, Ezeobi PM, Okwuraiwe
A, Audu RA, Okoye RN: Corrected and modified the original design,
reviewed, cleaned and managed the acquired data, revising the various
draft critically for important intellectual content and gave final
approval to the final version. David AN, Odunukwe NN, Onwujekwe DI,
Ujah IAO: Reviewed the original concept and design, interpreted
of data, revised the various drafts of article for important intellectual
contentand gave final approval to the final version. All the authors
have read and approved the final version of the manuscript.
The HIV Treatment Centre, Nigerian Institute of Medical Research Lagos, where this study was conducted is partly funded by AIDS Prevention Initiative Nigeria (APIN) through a grant from CDC, Nigeria. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding Organizations. We are grateful to all study participants. The management and program staff at the treatment centre are hereby acknowledged.
Table 1: Sociodemographic, reproductive and biologic characteristics of the 2391 pregnant HIV positive women studied (2006 -2011)
Table 2: Association between patient’s characteristics and Hepatitis B co-infection among HIV positive pregnant women
Table 3: Association between patient’s characteristics and Hepatitis C co-infection among HIV positive pregnant women
- Lai CL, Ratziu V, Yeun MF, Poynard T. Viral hepatitis B. Lancet 2003; 362(9401): 2089-94. Google Scholar
- Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997; 349(9061): 1269-76. Google Scholar
- Soriano V, Barreiro P, Nunez M. Management of chronic hepatitis B and C in HIV-coinfected patients. J AntimicrobChemother. 2006; 57(5): 815-818. Google Scholar
- Alberti A, Clumeck N, Collins S et al. Short statement
of the first European Consensus Conference on the treatment of chronic hepatitis
B and C in HIV co-infected patients. J Hepatol. 2005; 42(24): 615-624. Google
- Lee WM. Hepatitis B Virus infections. N Engl J Med 1997;337 (24):1733-4. Google Scholar
- Imade GE, Sagay AS, Ugwu BT, Thacher TD, Ford RW. Seroprevalence of Hepatitis B and Human Immunodeficiency Virus infections in pregnant women in Nigeria. Journal of Medic in the tropics. 2004; 6(2):15-21. Google Scholar
- Joint United Nations Programme on HIV/AIDS (UNAIDS). 2010 report on the global AIDS epidemic. Geneva, Switzerland: UNAIDS; 2010. http://www. unaids. org/globalreport/Global_report. htm. Accessed July 2013. PubMed | Google Scholar
- Wilcox. RD. Hepatitis B co-infection in pregnancy. HIV Clinician. 2010; 22(1): 5-6. PubMed | Google Scholar
- Lesi O A, Kehinde M O, Oguh DN, Amira CO. Hepatitis B and C virus infection in Nigerian patients with HIV/AIDS. Niger Postgrad Med J. 2007; 14(2):129-33. PubMed | Google Scholar
- Nwokedi EE, Epopees MA, Dutse AI. Human immunodeficiency virus and hepatitis B virus co infection among patients in Kano, Nigeria. Niger J Med. 2006; 15(3):227-9. PubMed | Google Scholar
- Denue BA, Ajayi B, Abja AU, Bukar AA, Akawu C, Ekong E, Alkali MB. A survey of Hepatitis B and C virus prevalence in Human immunodeficiency virus positive patients in a Tertiary health institution in North Eastern Nigeria. International Journal of Medicine and Medical Sciences. 2012; 4(1):13-18. Google Scholar
- Balogun TM, Emmanuel S, Ojerinde EF. HIV, Hepatitis B and C viruses? co-infection among patients in a Nigerian tertiary hospital. The Pan African Medical Journal. 2012; 12:100. PubMed | Google Scholar
- Thio CL, Seaberg EC, Skolasky R Jr, Phair J, Visscher B, Munoz A, Thomas DL. HIV-1, Hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002; 360(9349):1921-1926. Google Scholar
- Zimmerman RK, Ruben FL, Ahwesh ER. Hepatitis B virus Infection, hepatitis B vaccine and hepatitis B immune globulin. J Fam Pract. 1997; 45(4):295-315. Google Scholar
- Petrovic LM. HIV/HCV co-infection: histopathologic findings, natural history, fibrosis, and impact of antiretroviral treatment: a review article. Liver Int. 2007; 27(5): 598-606. Google Scholar
- Konopnicki D, Mocroft A, de Wit S et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005; 19(6): 593-601. Google Scholar
- The DAD Study Group. Liver-related deaths in persons infected with the human immunodeficiency virus: the DAD Study. Arch Intern Med. 2006; 166(15): 1632?1641. . Google Scholar
- Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, Koziel MJ. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: A meta-analysis. Clin Infect Dis. 2001;33(4):562-569. Google Scholar
- Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated withnevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections. Hepatology. 2002; 36(1):512-513. Google Scholar
- Eke AC, Eke UA, Okafor CI, Ezebialu IU, Ogbuagu C. Prevalence correlates and pattern of hepatitis B surface antigen in a low resource setting. Virology journal. 2011; 8:12-15. Google Scholar
- Pirillo MF, Bassani L, Germinario EA, Mancini MG, Vyankandondera J, Okong P, Vella S, Giuliano M. Seroprevalence of hepatitis B and C viruses among HIV-infected pregnant women in Uganda and Rwanda. J Med Virol. 2007; 79(12):1797-801. PubMed | Google Scholar
- Landes M, Newell ML, Barlow P, Fiore S, Malyuta R, Martinelli P et al. Hepatitis B or hepatitis C co-infection in HIV-infected pregnant women in Europe. HIV Medicine. 2008; (7)9:526-534. Google Scholar
- Adesina O, Oladokun A, Akinyemi O, Adedokun B, Awolude O, Odaibo G, Olaleye D, Adewole. Human immuno-deficiency virus and hepatitis B virus coinfection in pregnancy at the University College Hospital, Ibadan. Afr J Med Med Sci. 2010; 39(4):305-10. PubMed | Google Scholar
- Rouet F, Chaix ML, Inwoley A, Msellati P, Viho I, Combe P, Leroy V, Dabis F. HBV and HCV prevalence and viraemia in HIV-positive and HIV-negative pregnant women in Abidjan, Côte d'Ivoire: the ANRS 1236 study. J Med Virol. 2004;74(1):34-40. PubMed | Google Scholar
- Ezegbudo CN, Agbonlahor DE, Nwobu G, Igwe CU, Agba MI, Okpala HO, Ikaraoha CI. The Seroprevalence of Hepatitis B Surface Antigen and Human Immunodeficiency Virus Among Pregnant Women in Anambra State Nigeria. Shiraz E-Medical Journal. 2004; 5(5):1-8. Google Scholar
- Santiago-Munoz P, Roberts S, Sheffield J, McElwee B, Wendel GD 2005. Prevalence of hepatitis B and C in pregnant women who are infected with human immunodeficiency virus. Am J Obstr Gyn. 2005; 193(3):1270-3. PubMed | Google Scholar
- Allain JP, Candotti D, Soldan K, et al. The risk of hepatitis B virusinfection by transfusion in Kumasi, Ghana. Blood. 2003; 101(6): 2419-25. Google Scholar
- MF Yuen, HJ Yuan, DKH Wong, JCH Yuen, WM Wong, AOO Chan, BCY Wong, KC Lai, CL Lai. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications Gut. 2005; 54(11):11 1610-1614. Google Scholar
- J. Simpore, D. Ilboudo, A. Samandoulougou, P. Guardo, P. Castronovo, S. Musumeci. HCV and HIV Co-Infection in Pregnant Women attending St. Camille Medical Centre in Ouagadougou (Burkina Faso). Journal of medical Virology. 2004; 9999(2):1-5. PubMed | Google Scholar
- Thomas DL. Hepatitis C and human immunodeficiency virus infection. Hepatology. 2002; 36(5 Suppl 1):S201-9. PubMed | Google Scholar