|Year : 2015 | Volume
| Issue : 4 | Page : 516-521
Co-infections of hepatitis B and C with human immunodeficiency virus among adult patients attending human immunodeficiency virus outpatients clinic in Benin City, Nigeria
CK Ojide1, EI Kalu2, E Ogbaini-Emevon3, VU Nwadike4
1 Department of Medical Microbiology, Federal Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
2 Department of Medical Microbiology, Federal Medical Centre, Umuahia, Abia State, Nigeria
3 Institute of Lassa Fever Research, Irua Specialist Hospital, Irua, Edo State, Nigeria
4 Department of Medical Microbiology, Federal Medical Centre, Abeokuta, Nigeria
|Date of Acceptance||04-Jan-2015|
|Date of Web Publication||13-May-2015|
C K Ojide
Department of Medical Microbiology, Federal Teaching Hospital, Abakaliki, Ebonyi State
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Hepatitis B and C viral co-infections with human immunodeficiency virus (HIV) are known to affect progression, management, and outcome of HIV infection. This study was aimed to access the prevalence of hepatitis B and C co-infections in HIV-infected adult patients in the University of Benin Teaching Hospital with a view of understanding the gravity of this problem in the local population.
Methods: The descriptive cross-sectional study was carried out on 342 HIV-infected adult patients on highly active antiretroviral therapy attending HIV Outpatients Clinic of University of Benin Teaching Hospital, between April and September, 2011. Patients' sera were screened for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) using immunochromatographic-based kits. Clinical stage of HIV and CD4+ cell counts were equally evaluated. Data were analyzed using SPSS version 17.
Results: Of the 324 HIV-infected patients screened, 53 (15.5%) were positive for HBsAg, 24 (7.0%) positive for hepatitis C virus antibodies (HCV-Ab), while 2 (0.6%) were positive for both viruses. Seroprevalence of HBsAg was higher in male (17.8%) than in female (14.7%) (χ2 = 0.49, P = 0.49), while the reverse is the case for HCV-Ab; 7.1% for female and 6.7% for male (χ2 = 0.02, P = 0.88). Seroprevalences of HBsAg and HCV-Ab were also higher among patients in World Health Organization disease stages 3-4 and patients with CD4+ cell count ≤200 cell/ml compared to those in stages 1-2 and with CD4+ cell count >200 cell/ml.
Conclusion: Co-infection with hepatitis B virus and HCV among HIV/acquired immune deficiency syndrome (AIDS) patients is still a problem in our environment. Screening for these viruses among HIV/AIDS patients will allow for early detection and proper management.
Keywords: Benin, co-infection, hepatitis B virus, hepatitis C virus, human immunodeficiency virus/acquired immune deficiency syndrome
|How to cite this article:|
Ojide C K, Kalu E I, Ogbaini-Emevon E, Nwadike V U. Co-infections of hepatitis B and C with human immunodeficiency virus among adult patients attending human immunodeficiency virus outpatients clinic in Benin City, Nigeria. Niger J Clin Pract 2015;18:516-21
|How to cite this URL:|
Ojide C K, Kalu E I, Ogbaini-Emevon E, Nwadike V U. Co-infections of hepatitis B and C with human immunodeficiency virus among adult patients attending human immunodeficiency virus outpatients clinic in Benin City, Nigeria. Niger J Clin Pract [serial online] 2015 [cited 2019 Aug 24];18:516-21. Available from: http://www.njcponline.com/text.asp?2015/18/4/516/151790
| Introduction|| |
Hepatitis B and C co-infection with human immunodeficiency virus (HIV) have assumed a growing concern in public health especially in Sub-Saharan Africa. The three viral infections are not only endemic in the region;  they equally share similar routes of transmission such as injection drug use, sexual contact, or from mother to child during pregnancy or birth. Furthermore, there are reports suggesting a more rapid progression of viral hepatitis caused by Hepatitis B and C viruses to end-stage liver disease and death in HIV-infected patients. ,, The viral hepatitis agents, on the other hand, are reported to increase HIV replication, increase highly active antiretroviral therapy (HAART) related hepatotoxicity and decrease CD4 + cell count. , Some researchers have equally opined that as antiretroviral therapy programs in this region matures and people living with HIV/acquired immune deficiency syndrome (AIDS) (PLWHA) survives longer, the morbidity and mortality associated with co-infections will become increasingly important. 
Globally, 34 million people were living with HIV by the end of 2011. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 20 adults (4.9%) living with HIV and accounting for 69% of the people living with HIV worldwide.  In Nigeria, adult prevalence rate was estimated to be 3.7% at the end of 2011 and considering her population size of 162.2 million, an estimated 3.5 million Nigerians are living with HIV/AIDS, ranking Nigeria third among the countries with the highest HIV/AIDS burden in the world, next only to India and South Africa. 
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are equally endemic across African continent, Nigeria inclusive.  The prevalence of mono-infection for hepatitis B infection in her general population ranges from 9% to 39%,  more than 7% chronic carrier rate considered hyperendemic.  The prevalence rate of HCV in Nigeria is also considerably high ranging from 5.8% to 12.3%.  Due to the endemic nature of these viruses in the sub-Saharan region and the shared routes of transmission, co-infections of HIV-HBV or HIV-HCV or even the three viruses (HIV-HBV-HCV) are not uncommon. Prevalence of co-infection varies depending on the population studied. An earlier Nigerian study reported 11.9%, 4.8%, and 1% for HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections respectively.  Prevalence of HIV-HBV and HIV-HCV co-infections among Nigerian prison inmates was also reported as 2.7% and 0.7%, respectively.  In Ruwanda, prevalence of HIV-HBV and HIV-HCV co-infections, respectively, were reported as 5.2% and 5.7%.  Among HIV-infected pregnant women, prevalence of 4.9% and 0.6% in Uganda; and 2.4% and 4.9% in Ruwanda were recorded for HIV-HBV and HIV-HCV, respectively.  The difference in prevalence is thought to be due to the differential efficacies of these viruses to the types of exposures found in the various geographical regions. 
Expert guidelines developed in the United States and Europe recommend screening of all HIV-infected persons for infection with HCV and HBV and appropriate management of those found to be chronically infected.  In Nigeria, however, HIV-infected patients are not routinely screened for hepatitis viruses. Screening for HBV and HCV are only considered following observed deranged liver enzymes. This practice will not allow for early detection of co-infections and institution of proper management of cases. Again, data on the prevalence of co-infection in our environment are still relatively scarce. This study is, therefore, aimed at determining the prevalence of HBV and HCV co-infections in HIV-infected adult patients in our environment.
| Methods|| |
This is a cross-sectional study involving 342 HIV-infected adult patients on HAART attending the HIV Outpatients Clinic of the University of Benin Teaching Hospital between April and September 2011. This hospital is a 700 bed tertiary institution located and serving as a major referral center in the southern part of Nigeria. Informed consents were sought, and consecutively consenting patients were recruited into the study. Bio data and clinical histories were obtained through interviewer-administered structured questionnaires and patients' case notes. For the purpose of this study, participants were categorized into asymptomatic (stage 1 and 2) and symptomatic (stage 3 and 4) in line with World Health Organization (WHO) clinical staging system. 
The HIV status of participants was already determined through their plasma samples screened with two different methods namely; Abbott determine HIV 1 and 2 kit which is an in vitro visually read immunoassay (Abbot Japan C. Ltd., Tokyo, Japan) and HIV 1 and 2 STATPAK Assay kit, which is an immunochromatographic test for the qualitative detection of antibodies to HIV-1 and HIV-2 in human plasma (CHEMBIO Diagnostic system, Inc., New York, USA). These tests were carried out strictly following the manufacturers' instructions. Both methods have inherent quality controls that were used to validate results. Seropositivity for the two methods was used to classify patients as HIV infected.
Five milliliters of blood was taken from each of the HIV-infected patients and shared into a sterile unanticoagulated and ethylenediaminetetraacetic acid (EDTA) bottles. The former were centrifuged, sera separated, and stored at −20°C and later analyzed for both hepatitis B surface antigen (HBsAg) and anti-HCV using commercially available Clinotech diagnostics HBsAg and anti-HCV test kits (Canada), following the manufacturer's instructions. The test kits were based on immunochromatographic principles and designed to detect HBsAg and anti-HCV qualitatively with sensitivity of 99.8% and specificity of 100%. The specimen on EDTA bottles was used for CD4+ cell count using flow cytometry.
Data were analyzed using Data were analyzed using SPSS Statistics for Windows, Version 17.0 (Chicago, SPSS Inc.). Descriptive data were presented as mean ± standard deviation. Chi-square or Fisher's exact was used where appropriate to test the association. Statistical significance was presumed where P < 0.05.
| Results|| |
A total of 342 HIV-infected adult patients took part in the study comprising 90 (26.3%) males and 252 (73.7%) females giving a male to female ratio of 1:2.8. Their ages ranged between 19 and 69 with a mean age of 40 ± 10 years. 134 (39.2%) of the participants belonged to age group 31-40 years, followed by 89 (20.6%) in the age group 41-50 years, while only 5 (1.5%) were above 60 years. Following the WHO clinical staging system, 214 (62.6%) were in stages 1 and 2 and the remaining 128 (37.4%) were in stages 3 and 4. The CD4+ cell counts of 174 (50.8%) patients were ≤200/μl [Table 1].
Of the 324 HIV-infected patients screened, 53 (15.5%) were positive for HBsAg, 24 (7.0%) positive for hepatitis C virus antibodies, while 2 (0.6%) were positive for both viruses [Table 2]. Seroprevalence of HBsAg was found to be more in male (17.8%) than in female (14.7%), but this was not statistically significant (χ2 = 0.49, P = 0.49) as shown in [Table 3]. Seroprevalence of HBsAg was also found to hover within the range of 16.3-16.9% in age groups <20 years, 21-30 years, 31-40 years and 41-50 years, but dropped to 11.9% in age group 51-60 years and 0.0% in patients >60 years [Table 3]. Patients presenting with WHO disease stages 3-4 were affected more with hepatitis B infection than those with stages 1-2 (19.5% vs. 13.1%), (χ2 = 2.54, P = 0.11). Furthermore, patients with CD4+ cell count ≤200 cell/μl had a higher HBsAg seroprevalence of 18.4% compared to 12.5% recorded for those with CD4+ cell count >200 cell/μl (χ2 = 2.20, P = 0.14).
|Table 2: Seroprevalence of HBsAg, HCV-Ab, HBsAg/HCV-Ab among participants (n=342) |
Click here to view
[Table 4] shows the anti-HCV status of participants. Seroprevalence of anti-HCV was slightly higher in female patients (7.1%) than males (6.7%) (χ2 = 0.02, P = 0.88). Age group 31-40 years recorded the highest prevalence (9.7%), followed by 41-50 years (7.9%) and 21-30 years (6.1%), while patients that were ≤20 years and >60 years both recorded 0.0%. Patients presenting at stages 1-2 of WHO clinical staging had a nonsignificant lower anti-HCV seroprevalence of 6.5% than those at stages 3-4 (7.8%) (χ2 = 0.20, P = 0.66), just as patients with CD4 + cell count >200 cell/μl had a lower rate of 6.0% compared to 8.0% recorded for those with ≤200 cells/μl (χ2 = 0.88, P = 0.35) as shown in [Table 4].
| Discussion|| |
This survey aimed at determining the prevalence of hepatitis B and C infections in HIV-infected adult patients in the University of Benin Teaching Hospital revealed that 15.5% of our patients were HBsAg positive. In comparison with earlier studies carried out in Nigeria, this figure is higher than 11.9% reported in Ibadan,  6.6% in Nasarawa  and 2.7% in Ado Ekiti,  but lower than 20.6% documented in North Central Nigeria,  25.9% in Jos,  and 28.4% in Lagos.  Figures as high as 51.9% and 70.5% have equally been documented in Lagos  and Kano,  respectively, both being the most populated and highly commercially active cities in Nigeria. Our finding is also comparable to 17.3% reported in Tanzania,  but lower than 6.0% reported in South Africa. Again from our study, 7.0% of HIV-infected patients equally harbor HCV. This is comparable to 8.2% reported in Abuja, Nigeria,  but contradicts 14.7% reported in Lagos,  no case of HIV/HCV co-infection reported among asymptomatic pregnant women attending antenatal clinic  and 4.4% among HIV-infected patients  documented in earlier studies carried out in Benin, Nigeria.
Although co-infection with HBV from this study is higher than with HCV, a recurring finding in almost all the studies in Nigeria, the prevalence of co-infection for both viruses is still considerably high. This is understandably so since these viruses on their own are not only endemic in our environment, but also sharing similar routes of transmission. Apart from confirming the endemicity of co-infections by both viruses in our environment as reported by previous researchers, our finding also underscores the need to intensify efforts to get HIV infected individuals routinely screened for both HBV and HCV in Nigeria as recommended by expert guidelines developed in United State and Europe.  Such guideline, if adopted, will lead to early detection of cases of co-infection, proper adjustment of management strategies and better outcome.
Dual co-infection with HBV and HCV has been documented before in similar studies. Our study revealed that 0.6% of our patients had dual co-infection, a figure comparable to 0.3% recorded in Kenya  and 1.0% reported in Ibadan, Nigeria.  Relatively higher prevalence of HIV/HBV/HCV co-infections has been documented in Lagos (3.9%)  and North Central Nigeria (7.2%).  A Tanzanian study reported 3.9% prevalence of HIV/HBV/HCV co-infections.  Dual co-infection with HBV and HCV in PLWHA is an interesting observation made in this study although only two case (0.6%) were detected, comprising 34-year-old male and 41-year-old female, both presenting in stage 4 with CD4+ count <100 cell/μl. Further studies involving the greater number of dual co-infection will be enriching and therefore advocated.
Male HIV-infected patients were affected more by HBV and females by HCV from our study. Similar finding was reported in Lagos, Nigeria,  and Tanzania.  There are, however, conflicting reports regarding male or female predominance for co-infection with either of these viruses. ,, The reason for this is not obvious, but may be due to the epidemiological differences in the different study populations and variations in methodology. Age-specific prevalence of HBV co-infection from this study was higher in the younger patients (<20-50 years) than their older counterpart (51 to >60 years). This may be due to the fact that the younger patients are more likely exposed to risky behaviors than the older ones. This pattern of presentation was, however, lacking for HIV/HCV co-infection where prevalence rose with age for a while, peaked at 31-40 years before declining again.
Regarding clinical stage and CD4+ cell count, prevalence of both HIV/HBV and HIV/HCV was higher in stages 3-4 and CD4+ <200 cell/μl, respectively, than observed in stages 1-2 and CD4+ ≥200 cell/μl. These higher prevalence rates observed in these groups are, however, not statistically significant. This is similar to findings from other studies. ,
| Conclusion|| |
Co-infection with HBV and HCV among HIV/AIDS patients is still a problem in our environment as 15.5% and 7.0% of these patients were seropositive for HBV and HCV respectively; and 0.6% for both viruses. Screening for these viruses among HIV/AIDS patients is, therefore, advocated as this will allow for early detection and proper management.
The window period of the Australian antigen, time between the disappearance of HBsAg and appearance of anti-HBs was not considered in this study. IgM anti-HBc serological marker would have been very useful in detecting those in the window period, but this was not done in the study. HBV DNA would have as well equally helped in this regard but was not tested in the population due to lack of facility for the test and high cost of sending samples out for such test.
| Acknowledgments|| |
The Authors wish to acknowledg the co-operation of the staff of the HIV Outpatient Clinic, PEPFAR (Presidential Emergency Plan for AIDS Relief) and Medical Microbiology Departments of University of Benin Teaching Hospital.
| References|| |
Modi AA, Feld JJ. Viral hepatitis and HIV in Africa. AIDS Rev 2007;9:25-39.
Highleyman L. HIV and hepatitis C coinfection. BETA 2003;15:32-44.
Piliero PJ, Faragon JJ. Case report. Hepatitis B virus and HIV coinfection. AIDS Read 2002;12:443-4, 8.
Thio C. Hepatitis B virus infection in HIV-infected persons. Curr Hepat Rep 2004;3:91-7.
Leeratanapetch N, Suseangrut W. Hepatitis B Virus and Hepatitis C Virus Co-Infection with HIV Patients at Khon Kaen Hospital. Khon Kaen Hosp Med J 2008;32:229-38.
Mohammadi M, Talei G, Sheikhian A, Ebrahimzade F, Pournia Y, Ghasemi E, et al.
Survey of both hepatitis B virus (HBsAg) and hepatitis C virus (HCV-Ab) coinfection among HIV positive patients. Virol J 2009;6:202.
Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepatol 2008;48:353-67.
UNAIDS Report on the Global AIDS Epidemic; 2011.
National Agency for Control of AIDS (NACA)-World Bank HIV/AIDS Programme Development Project 2 Progress Q1 Report; 2012.
Emechebe GO, Emodi IJ, Ikefuna AN, Ilechukwu GC, Igwe WC, Ejiofor OS, et al
. Hepatitis B virus infection in Nigeria - A review. Niger Med J 2009;50:18-22.
Kiire CF. The epidemiology and control of hepatitis B in sub-Saharan Africa. Prog Med Virol 1993;40:141-56.
Eze EU, Ofili AN, Onunu AN. Prevalence of Hepatitis C virus in HIV infected Persons in a tertiary hospital in Nigeria. Niger J Clin Pract 2010;13:41-6.
Otegbayo JA, Taiwo BO, Akingbola TS, Odaibo GN, Adedapo KS, Penugonda S, et al.
Prevalence of hepatitis B and C seropositivity in a Nigerian cohort of HIV-infected patients. Ann Hepatol 2008;7:152-6.
Adoga MP, Banwat EB, Forbi JC, Nimzing L, Pam CR, Gyar SD, et al.
Human immunonodeficiency virus, hepatitis B virus and hepatitis C virus: Sero-prevalence, co-infection and risk factors among prison inmates in Nasarawa State, Nigeria. J Infect Dev Ctries 2009;3:539-47.
Rusine J, Ondoa P, Asiimwe-Kateera B, Boer KR, Uwimana JM, Mukabayire O, et al.
High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda. PLoS One 2013;8:e63303.
Pirillo MF, Bassani L, Germinario EA, Mancini MG, Vyankandondera J, Okong P, et al.
Seroprevalence of hepatitis B and C viruses among HIV-infected pregnant women in Uganda and Rwanda. J Med Virol 2007;79:1797-801.
Kumar R, Singla V, Kacharya SK. Impact and management of hepatitis B and hepatitis C virus co-infection in HIV patients. Trop Gastroenterol 2008;29:136-47.
World Health Organization. WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-Related Disease in Adults and Children. Geneva, Switzerland: World Health Organization; 2007.
Adekunle AE, Oladimeji AA, Temi AP, Adeseye AI, Akinyeye OA, Taiwo RH. Baseline CD4+T lymphocyte cell counts, hepatitis B and C viruses seropositivity in adults with Human Immunodeficiency Virus infection at a tertiary hospital in Nigeria. Pan Afr Med J 2011;9:6.
Forbi JC, Gabadi S, Alabi R, Iperepolu HO, Pam CR, Entonu PE, et al.
The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) type-1 on CD4+lymphocyte levels in the highly HIV infected population of North-Central Nigeria. Mem Inst Oswaldo Cruz 2007;102:535-7.
Uneke CJ, Ogbu O, Inyama PU, Anyanwu GI, Njoku MO, Idoko JH. Prevalence of hepatitis-B surface antigen among blood donors and human immunodeficiency virus-infected patients in Jos, Nigeria. Mem Inst Oswaldo Cruz 2005;100:13-6.
Balogun TM, Emmanuel S, Ojerinde EF. HIV, Hepatitis B and C viruses' coinfection among patients in a Nigerian tertiary hospital. Pan Afr Med J 2012;12:100.
Iwalokun BA, Hodonu SO, Olaleye BM, Olabisi OA. Seroprevalence and biochemical features of hepatitis B surface antigenemia in patients with HIV-1 infection in Lagos, Nigeria. Afr J Med Med Sci 2006;35:337-43.
Nwokedi EE, Emokpae MA, Dutse AI. Human immunodeficiency virus and hepatitis B virus co-infection among patients in Kano Nigeria. Niger J Med 2006;15:227-9.
Nagu TJ, Bakari M, Matee M. Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania. BMC Public Health 2008;8:416.
Agwale SM, Tanimoto L, Womack C, Odama L, Leung K, Duey D, et al.
Prevalence of HCV coinfection in HIV-infected individuals in Nigeria and characterization of HCV genotypes. J Clin Virol 2004;31 Suppl 1:S3-6.
Onakewhor JU, Okonofua FE. The prevalence of dual human immunodeficiency virus/hepatitis C virus (HIV/HCV) infection in asymptomatic pregnant women in Benin City, Nigeria. Afr J Reprod Health 2009;13:97-108.
Harania RS, Karuru J, Nelson M, Stebbing J. HIV, hepatitis B and hepatitis C coinfection in Kenya. AIDS 2008;22:1221-2.
Lesi OA, Kehinde MO, Oguh DN, Amira CO. Hepatitis B and C virus infection in Nigerian patients with HIV/AIDS. Niger Postgrad Med J 2007;14:129-33.
Anigilaje EA, Olutola A. Prevalence and Clinical and immunoviralogical profile of human immunodeficiency virus-hepatitis B coinfection among children in an antiretroviral therapy programme in Benue State, Nigeria. ISRN Pediatr 2013;2013:932697.
Rawizza H, Ochigbo S, Chang C, Melonil M, Oguche S, Osinusil K, et al
. Prevalence of Hepatitis Co-infection Among HIV-Infected Nigerian Children in the Harvard PEPFAR ART Program. Conference on Retroviruses and Opportunistic Infections; February 16 th
; San Francisco CA; 2010.
[Table 1], [Table 2], [Table 3], [Table 4]
|This article has been cited by|
||Changes in liver stiffness after ART initiation in HIV-infected Nigerian adults with and without chronic HBV
| ||Jennifer L Grant,Patricia Agaba,Placid Ugoagwu,Auwal Muazu,Jonathan Okpokwu,Samuel Akpa,Stephen Machenry,Godwin Imade,Oche Agbaji,Chloe L Thio,Robert Murphy,Claudia Hawkins |
| ||Journal of Antimicrobial Chemotherapy. 2019; |
|[Pubmed] | [DOI]|
||Hepatitis B virus and HIV coinfection among adults residing in Cameroon: A systematic review and meta-analysis of prevalence studies
| ||Jean Joel Bigna,Jan René Nkeck,Anderson Ngouo,Ulrich Flore Nyaga,Jean Jacques Noubiap |
| ||Infection, Disease & Health. 2018; 23(3): 170 |
|[Pubmed] | [DOI]|
||Epidemiology of HBV in pregnant women, South West Nigeria
| ||Glory Atilola,Tomisin Obadara,Mayowa Randle,Isaac Komolafe O.,Gbenga Odutolu,Josephine Olomu,Laide Adenuga |
| ||Journal of Epidemiology and Global Health. 2018; |
|[Pubmed] | [DOI]|
||A very high frequency of hepatitis B and C virus infections during an active screening campaign in Abidjan
| ||A. Kouassi-M’Bengue,Abdoulaye Ouattara,Emile Allah-Kouadio,Daouda Sevede,Moussa Doumbia,M. Dosso |
| ||African Journal of Microbiology Research. 2017; 11(1): 8 |
|[Pubmed] | [DOI]|
||Screening Outcomes of Hepatitis B and E among HIV Patients on HAART in Osogbo, South Western Nigeria
| ||Bolaji E. Egbewale,Victor O. Mabayoje,M. A. Muhibi,A. F. Mustapha,Calistus A. Akinleye |
| ||World Journal of AIDS. 2016; 06(04): 205 |
|[Pubmed] | [DOI]|
||Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia
| ||Jamil A. Al-Mughales |
| ||Journal of Medical Virology. 2016; 88(9): 1545 |
|[Pubmed] | [DOI]|