Hepatitis B virus seromarkers among HIV infected adults on ART: An unmet need for HBV screening in eastern Ethiopia

Autoři: Desalegn Admassu Ayana aff001;  Andargachew Mulu aff001;  Adane Mihret aff001;  Berhanu Seyoum aff001;  Abraham Aseffa aff001;  Rawleigh Howe aff001
Působiště autorů: College of Health and Medical Sciences, Haramaya University, Oromia, Ethiopia aff001;  Armauer Hansen Research Institute, Addis Ababa, Ethiopia aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0226922


Progression of chronic HBV to cirrhosis, end-stage liver disease (ESLD), and hepatocellular carcinoma (HCC) is more rapid in HIV positive individuals than those with HBV alone; however, the distribution of HBV seromarkers in HIV infected individuals on antiretroviral therapy (ART) is not well described. To address this problem, we assessed the distribution of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) among HIV infected adults on ART in Eastern Ethiopia. A cross-sectional study was conducted from September 2017 to February 2018. Socio-demographic, behavioral and health related factors, and clinical data were collected using questionnaire and checklist. Plasma samples were tested for HBsAg, anti-HBc and anti-HBs seromarkers using ELISA. Data were double entered into EpiData 3.1, cleaned, exported to and analyzed using STATA 13. Descriptive and logistic regression analysis were conducted and statistical significance was decided at p≤0.05. A total of 901 participants were included and the prevalence of HBsAg was found to be 11.7% [95%CI (10, 14)]. Among the co-infected, 47.6% were also positive for anti-HBc, of which 58% were on an ART containing tenofovir (TDF). Among those screened for the three seromarkers, 38.1% were negative for all and 21% were positive only for anti-HBc (IAHBc). Being single, history of genital discharge and taking ART with TDF combination were significantly associated with HBV co-infection (p≤0.05). There is high burden HBV co-infection among individuals on ART. The unmet need of HBV screening prior to ART initiation leaves many co-infected individuals without appropriate management including therapy, close monitoring or vaccination when indicated, impacting disease prevention.

Klíčová slova:

Co-infections – Ethiopia – Hepatitis B – Hepatitis B virus – HIV infections – Opportunistic infections


1. UNAIDS. Global AIDS update. 2019 Fact Sheet. 2019.

2. Singh AE, Wong T. Background document: HIV and hepatitis B co-infection. Department of HIV/AIDS, World Health Organization. 2009.

3. Luetkemeyer A. Current issues in the diagnosis and management of tuberculosis and HIV coinfection in the United States. Topics in HIV medicine: a publication of the International AIDS Society, USA. 2010;18(4):143–8.

4. Burnett R, Francois G, Kew M, Leroux‐Roels G, Meheus A, Hoosen A, et al. Hepatitis B virus and human immunodeficiency virus co‐infection in sub‐Saharan Africa: a call for further investigation. Liver international. 2005;25(2):201–13. doi: 10.1111/j.1478-3231.2005.01054.x 15780040

5. Chung RT. Hepatitis C and B viruses: the new opportunists in HIV infection. Top HIV Med. 2006;14(2):78–83. 16835462

6. Chun HM, Roediger MP, Hullsiek KH, Thio CL, Agan BK, Bradley WP, et al. Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters. Journal of Infectious Diseases. 2011;205(2):185–93. doi: 10.1093/infdis/jir720 22147794

7. Konopnicki D, Mocroft A, De Wit S, Antunes F, Ledergerber B, Katlama C, 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. doi: 10.1097/01.aids.0000163936.99401.fe 15802978

8. Iser DM, Warner N, Revill PA, Solomon A, Wightman F, Saleh S, et al. Co-infection of hepatic cell lines with HIV-hepatitis B virus (HBV) leads to an increase in intracellular hepatitis B surface antigen (HBsAg). Journal of Virology. 2010.

9. Allain J-P. Occult hepatitis B virus infection. Transfusion clinique et biologique. 2004;11(1):18–25. doi: 10.1016/j.tracli.2003.11.007 14980545

10. Coffin CS, Mulrooney-Cousins PM, Osiowy C, van der Meer F, Nishikawa S, Michalak TI, et al. Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy. Journal of clinical virology. 2014;60(4):347–53. doi: 10.1016/j.jcv.2014.04.021 24881491

11. Mphahlele MJ, Lukhwareni A, Burnett RJ, Moropeng LM, Ngobeni JM. High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa. Journal of clinical virology. 2006;35(1):14–20. doi: 10.1016/j.jcv.2005.04.003 15916918

12. WHO. Guidelines on hepatitis B and C testing: World Health Organization; 2017.

13. FMOH. 2016_FMOH_Guideline for prevention and Control of Viral Hepatitis in Ethiopia. Guideline. 2016.

14. WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach: World Health Organization; 2016.

15. FMOH. National guidelines for comprehensive HIV prevention, care and treatment. Addis Ababa: Ministry of Health. 2017.

16. Bozdayi A, Uzunalimoğlu Ö, Türkyilmaz A, Aslan N, Sezgin O, Sahin T, et al. YSDD: a novel mutation in HBV DNA polymerase confers clinical resistance to lamivudine. Journal of viral hepatitis. 2003;10(4):256–65. doi: 10.1046/j.1365-2893.2003.00435.x 12823591

17. Manyazewal T, Sisay Z, Biadgilign S, Abegaz WE. Hepatitis B and hepatitis C virus infections among antiretroviral-naive and -experienced HIV co-infected adults. J Med Microbiol. 2014;63(Pt 5):742–7. doi: 10.1099/jmm.0.063321-0 24757219.

18. Negero A, Sisay Z, Medhin G. Prevalence of Hepatitis B surface antigen (HBsAg) among visitors of Shashemene General Hospital voluntary counseling and testing center. BMC research notes. 2011;4(1):35.

19. Belayneh F. Prevalence of Hepatitis B Virus Infection and Associated Factors among HIV Positive Adults Attending ART Clinic at Hawassa Referral Hospital, SNNPR, Ethiopia. OALib. 2015;02(05):1–7. doi: 10.4236/oalib.1101490

20. Habte Y, Seyoum B, Alemayehu T. Hepatitis B Virus Infection and Associated Factors among Blood Donors at Dire Dawa, Eastern Ethiopia. Journal of Antivirals & Antiretrovirals. 2016;08(04). doi: 10.4172/jaa.1000144

21. Yemanebrhane N, Addise D, Abebe N, Abebe F, Shewaamare A, Tsegaye A. Magnitude of Hepatitis B Virus and Hepatitis C Virus among HAART Taking Patients and Association with Liver and Renal Function and CD4+ T Cells Level. Journal of AIDS & Clinical Research. 2017;08(06). doi: 10.4172/2155-6113.1000702

22. Weldemhret L, Asmelash T, Belodu R, Gebreegziabiher D. Sero-prevalence of HBV and associated risk factors among HIV positive individuals attending ART clinic at Mekelle hospital, Tigray, Northern Ethiopia. AIDS research and therapy. 2016;13(1):6.

23. Deressa T, Damtie D, Fonseca K, Gao S, Abate E, Alemu S, et al. The burden of hepatitis B virus (HBV) infection, genotypes and drug resistance mutations in human immunodeficiency virus-positive patients in Northwest Ethiopia. PLoS One. 2017;12(12):e0190149. doi: 10.1371/journal.pone.0190149 29281718; PubMed Central PMCID: PMC5744989.

24. Shimelis T, Tassachew Y, Tadewos A, Hordofa MW, Amsalu A, Tadesse BT, et al. Coinfections with hepatitis B and C virus and syphilis among HIV-infected clients in Southern Ethiopia: a cross-sectional study. HIV/AIDS (Auckland, NZ). 2017;9:203.

25. Belayneh F. Prevalence of Hepatitis B Virus Infection and Associated Factors among HIV Positive Adults Attending ART Clinic at Hawassa Referral Hospital, SNNPR. Ethiopia OALib. 2015;2(05):1–7.

26. Belyhun Y, Maier M, Mulu A, Diro E, Liebert UG. Hepatitis viruses in Ethiopia: a systematic review and meta-analysis. BMC Infect Dis. 2016;16(1):761. doi: 10.1186/s12879-016-2090-1 27993129; PubMed Central PMCID: PMC5168848.

27. WHO. Global hepatitis report 2017: World Health Organization; 2017.

28. Barth RE, Huijgen Q, Taljaard J, Hoepelman AI. Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis. International Journal of Infectious Diseases. 2010;14(12):e1024–e31. doi: 10.1016/j.ijid.2010.06.013 20870439

29. Wondimeneh Y, Alem M, Asfaw F, Belyhun Y. HBV and HCV seroprevalence and their correlation with CD4 cells and liver enzymes among HIV positive individuals at University of Gondar Teaching Hospital, Northwest Ethiopia. Virology journal. 2013;10(1):171.

30. EPHIA2017-2018. Ethiopia Population-Based HIV Impact Assessment. Summary sheet. 2018.

31. Isaakidis P MH, Zachariah R, Da Silva EA, Varghese B, et al… Treatment outcomes in a cohort of patients with chronic hepatitis B and human immunodeficiency virus co-infection in Mumbai, India. Int Health. 2012;4((4)):239–45. doi: 10.1016/j.inhe.2012.04.002 24029669

32. Lule N, Nyawira B. Guidelines for the Treatment of Chronic Hepatitis B and C Viral Infections in Kenya. Nairobi: Gastroenterology Society of Kenya; 2012.

33. Ocana S, Casas ML, Buhigas I, Lledo JL. Diagnostic strategy for occult hepatitis B virus infection. World journal of gastroenterology: WJG. 2011;17(12):1553. doi: 10.3748/wjg.v17.i12.1553 21472120

34. Busch MP. Should HBV DNA NAT replace HBsAg and/or anti-HBc screening of blood donors? Transfusion clinique et biologique. 2004;11(1):26–32. doi: 10.1016/j.tracli.2003.12.003 14980546

35. Shimelis T, Torben W, Medhin G, Tebeje M, Andualm A, Demessie F, et al. Hepatitis B virus infection among people attending the voluntary counselling and testing centre and anti-retroviral therapy clinic of St Paul's General Specialised Hospital, Addis Ababa, Ethiopia. Sex Transm Infect. 2008;84(1):37–41. doi: 10.1136/sti.2007.027326 17804606.

36. Soriano V, Puoti M, Peters M, Benhamou Y, Sulkowski M, Zoulim F, et al. Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. Aids. 2008;22(12):1399–410. doi: 10.1097/QAD.0b013e3282f8b46f 18614862

37. Webster GJ, Reignat S, Maini MK, Whalley SA, Ogg GS, King A, et al. Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms. Hepatology. 2000;32(5):1117–24. doi: 10.1053/jhep.2000.19324 11050064

38. Hollinger FB. Hepatitis B virus infection and transfusion medicine: science and the occult. Transfusion. 2008;48(5):1001–26. doi: 10.1111/j.1537-2995.2008.01701.x 18454738

39. CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: Immunization of Adults. MMWR 2006;55((No. RR-16)):1–33.

40. Ponde RA, Cardoso DD, Ferro MO. The underlying mechanisms for the 'anti-HBc alone' serological profile. Arch Virol. 2010;155(2):149–58. doi: 10.1007/s00705-009-0559-6 20091193.

41. Wu J-F, Ni Y-H, Chen H-L, Hsu H-Y, Chang M-H. The impact of hepatitis B virus precore/core gene carboxyl terminal mutations on viral biosynthesis and the host immune response. Journal of Infectious Diseases. 2014;209(9):1374–81. doi: 10.1093/infdis/jit638 24273041

42. Mast E, Weinbaum C, Fiore A, Alter M, Bell B, Finelli L, et al. Centers for Disease Control and Prevention (CDC) A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1–33.

43. Kang SY, Kim MHa, Lee WI. The prevalence of “anti‐HBc alone” and HBV DNA detection among anti‐HBc alone in Korea. Journal of medical virology. 2010;82((9)):1508–14. doi: 10.1002/jmv.21862 20648604

44. Iser DM, Avihingsanon A, Wisedopas N, Thompson AJ, Boyd A, Matthews GV, et al. Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression. Aids. 2011;25(2):197–205. doi: 10.1097/QAD.0b013e3283410ccb 21076271

45. Melegari M, Bruno S, Wands JR. Properties of hepatitis B virus pre-S1 deletion mutants. Virology. 1994;199(2):292–300. doi: 10.1006/viro.1994.1127 8122362

46. Makondo E, Bell TG, Kramvis A. Genotyping and molecular characterization of hepatitis B virus from human immunodeficiency virus-infected individuals in southern Africa. PLoS One. 2012;7(9):e46345. doi: 10.1371/journal.pone.0046345 23029487

47. Salisse J, Sureau C. A function essential to viral entry underlies the hepatitis B virus “a” determinant. Journal of virology. 2009;83(18):9321–8. doi: 10.1128/JVI.00678-09 19570861

48. Shire NJ, Rouster SD, Stanford SD, Blackard JT, Martin CM, Fichtenbaum CJ, et al. The prevalence and significance of occult hepatitis B virus in a prospective cohort of HIV-infected patients. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2007;44(3):309–14. doi: 10.1097/QAI.0b013e31802e29a9 17159656

49. Tsui JI, French AL, Seaberg EC, Augenbraun M, Nowicki M, Peters M, et al. Prevalence and long-term effects of occult hepatitis B virus infection in HIV-infected women. Clinical Infectious Diseases. 2007;45(6):736–40. doi: 10.1086/520989 17712758

50. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. Journal of hepatology. 2007;46(1):160–70. doi: 10.1016/j.jhep.2006.10.007 17112622

51. FMOH. Guideline for prevention and Control of Viral Hepatitis in Ethiopia. 2016.

52. Yared HB, Muluken DM, Solomon GS, Helmut K. Higher prevalence of Hepatitis B virus Infection among ARV- exposed than naive HIV-infected individuals in North Shewa Zone, Ethiopia. Journal of AIDS and HIV Research. 2015;7(1):10–7. doi: 10.5897/jahr2014.0313

53. Saha D, Pal A, Biswas A, Panigrahi R, Sarkar N, Sarkar J, et al. Characterization of treatment-naive HIV/HBV co-infected patients attending ART clinic of a tertiary healthcare centre in eastern India. PLoS One. 2013;8(8):e73613. doi: 10.1371/journal.pone.0073613 24023688

54. 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(5):e63303. doi: 10.1371/journal.pone.0063303 23717409

55. Balew M, Moges F, Yismaw G, Unakal C. Assessment of hepatitis B virus and hepatitis C virus infections and associated risk factors in HIV infected patients at Debretabor hospital, South Gondar, Northwest Ethiopia. Asian Pacific Journal of Tropical Disease. 2014;4(1):1–7. doi: 10.1016/s2222-1808(14)60304-2

56. Abebe A, Nokes D, Dejene A, Enquselassie F, Messele T, Cutts F. Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control. Epidemiology & Infection. 2003;131(1):757–70.

Článok vyšiel v časopise


2019 Číslo 12