Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa

Authors: Tongai Gibson Maponga, Monique I. Andersson, Christoffel J. van Rensburg, Joop E. Arends, Jantjie Taljaard, Wolfgang Preiser, Richard H. Glashoff

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection.

Methods

We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed.

Results

HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17–53) and %CD8+/PD-1 (median 22%, interquartile range: 15–33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation.

Discussion

Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.
Appendix
Available only for authorised users
Literature
1.
Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology. 2009;49(S5):S138–45.CrossRefPubMed
2.
Thio CL, Seaberg EC, Skolasky R Jr, Phair J, Visscher B, Munoz A, Thomas DL, Multicenter ACS. HIV-1, hepatitis B virus, and risk of liver-related mortality in the multicenter cohort study (MACS). Lancet. 2002;360(9349):1921–6.CrossRefPubMed
3.
Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, Degott C, Benhamou JP, Erlinger S, Valla D, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology. 1999;29(4):1306–10.CrossRefPubMed
4.
Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, Zilmer K, Vella S, Kirk O, Lundgren JD, 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.CrossRefPubMed
5.
Hoffmann CJ, Seaberg EC, Young S, Witt MD, D'Acunto K, Phair J, Thio CL. Hepatitis B and long-term HIV outcomes in coinfected HAART recipients. AIDS. 2009;23(14):1881–9.CrossRefPubMedPubMedCentral
6.
Tran TT. Immune tolerant hepatitis B: a clinical dilemma. Gastroenterol Hepatol (N Y). 2011;7(8):511–6.
7.
Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.CrossRefPubMed
8.
Sandler NG, Koh C, Roque A, Eccleston JL, Siegel RB, Demino M, Kleiner DE, Deeks SG, Liang TJ, Heller T, et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology. 2011;141(4):1220-30. 1230 e1221-1223.
9.
10.
Mimura Y, Sakisaka S, Harada M, Sata M, Tanikawa K. Role of hepatocytes in direct clearance of lipopolysaccharide in rats. Gastroenterology. 1995;109(6):1969–76.CrossRefPubMed
11.
Tilton JC, Johnson AJ, Luskin MR, Manion MM, Yang J, Adelsberger JW, Lempicki RA, Hallahan CW, McLaughlin M, Mican JM, et al. Diminished production of monocyte proinflammatory cytokines during human immunodeficiency virus viremia is mediated by type I interferons. J Virol. 2006;80(23):11486–97.CrossRefPubMedPubMedCentral
12.
Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem. 1999;274(16):10689–92.CrossRefPubMed
13.
Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol. 2006;80(6):1197–213.CrossRefPubMed
14.
Marcellin P, Ziol M, Bedossa P, Douvin C, Poupon R, de Ledinghen V, Beaugrand M. Non-invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B. Liver Int. 2009;29(2):242–7.CrossRefPubMed
15.
Garson JA, Grant PR, Ayliffe U, Ferns RB, Tedder RS. Real-time PCR quantitation of hepatitis B virus DNA using automated sample preparation and murine cytomegalovirus internal control. J Virol Methods. 2005;126(1–2):207–13.CrossRefPubMed
16.
Hoffmann CJ, Thio CL. Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. Lancet Infect Dis. 2007;7(6):402–9.CrossRefPubMed
17.
Hoffmann CJ, Charalambous S, Martin DJ, Innes C, Churchyard GJ, Chaisson RE, Grant AD, Fielding KL, Thio CL. Hepatitis B virus infection and response to antiretroviral therapy (ART) in a south African ART program. Clin Infect Dis. 2008;47(11):1479–85.CrossRefPubMedPubMedCentral
18.
Idoko J, Meloni S, Muazu M, Nimzing L, Badung B, Hawkins C, Sankale JL, Ekong E, Murphy R, Kanki P, et al. Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria. Clin Infect Dis. 2009;49(8):1268–73.CrossRefPubMedPubMedCentral
19.
Wandeler G, Gsponer T, Bihl F, Bernasconi E, Cavassini M, Kovari H, Schmid P, Battegay M, Calmy A, Egger M, et al. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study. J Infect Dis. 2013;208(9):1454–8.CrossRefPubMed
20.
Nebbia G, Peppa D, Schurich A, Khanna P, Singh HD, Cheng Y, Rosenberg W, Dusheiko G, Gilson R, ChinAleong J, et al. Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection. PLoS One. 2012;7(10):e47648.CrossRefPubMedPubMedCentral
21.
Lu W, Mehraj V, Vyboh K, Cao W, Li T, Routy JP. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. J Int AIDS Soc. 2015;18:20052.CrossRefPubMedPubMedCentral
22.
Hamers RL, Zaaijer HL, Wallis CL, Siwale M, Ive P, Botes ME, Sigaloff KC, Hoepelman AI, Stevens WS, Rinke de Wit TF, et al. HIV-HBV coinfection in southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes. J Acquir Immune Defic Syndr. 2013;64(2):174–82.CrossRefPubMed
23.
Huang AJ, Nunez M. Outcomes in HIV/HBV-Coinfected patients in the Tenofovir era are greatly affected by immune suppression. J Int Assoc Provid AIDS Care. 2015;14(4):360–8.CrossRefPubMed
24.
Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, et al. Tenofovir Disoproxil fumarate versus Adefovir Dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359(23):2442–55.CrossRefPubMed
25.
Thio CL, Smeaton L, Hollabaugh K, Saulynas M, Hwang H, Saravanan S, Kulkarni S, Hakim J, Nyirenda M, Iqbal HS, et al. Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks. AIDS. 2015;29(10):1173–82.CrossRefPubMedPubMedCentral
26.
Andersson MI, Maponga TG, Ijaz S, Barnes J, Theron GB, Meredith SA, Preiser W, Tedder RS. The epidemiology of hepatitis B virus infection in HIV-infected and HIV-uninfected pregnant women in the western cape, South Africa. Vaccine. 2013;31(47):5579–84.CrossRefPubMedPubMedCentral
27.
Di Bisceglie AM, Maskew M, Schulze D, Reyneke A, McNamara L, Firnhaber C. HIV-HBV coinfection among south African patients receiving antiretroviral therapy. Antivir Ther. 2010;15(3 Pt B):499–503.CrossRefPubMedPubMedCentral
28.
Oshitani H, Kasolo FC, Mpabalwani M, Mizuta K, Luo NP, Suzuki H, Numazaki Y. Prevalence of hepatitis B antigens in human immunodeficiency virus type 1 seropositive and seronegative pregnant women in Zambia. Trans R Soc Trop Med Hyg. 1996;90(3):235–6.CrossRefPubMed
29.
Kosi L, Reiberger T, Payer BA, Grabmeier-Pfistershammer K, Strassl R, Rieger A, Peck-Radosavljevic M. Five-year on-treatment efficacy of lamivudine-, tenofovir- and tenofovir + emtricitabine-based HAART in HBV-HIV-coinfected patients. J Viral Hepat. 2012;19(11):801–10.CrossRefPubMed
30.
Hawkins C, Agbaji O, Ugoagwu P, Thio CL, Auwal MM, Ani C, Okafo C, Wallender E, Murphy RL. Assessment of liver fibrosis by transient Elastography in patients with HIV and hepatitis B virus coinfection in Nigeria. Clin Infect Dis. 2013;57(12):e189–92.CrossRefPubMedPubMedCentral
31.
Stabinski L, Reynolds SJ, Ocama P, Laeyendecker O, Ndyanabo A, Kiggundu V, Boaz I, Gray RH, Wawer M, Thio C, et al. High prevalence of liver fibrosis associated with HIV infection: a study in rural Rakai, Uganda. Antivir Ther. 2011;16(3):405–11.CrossRefPubMedPubMedCentral
32.
Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo ME, Casado R, Galindo L, Garcia-Gasco P, Garcia-Samaniego J, Soriano V. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15(3):165–72.PubMed
33.
Vlahakis SR, Villasis-Keever A, Gomez TS, Bren GD, Paya CV. Human immunodeficiency virus-induced apoptosis of human hepatocytes via CXCR4. J Infect Dis. 2003;188(10):1455–60.CrossRefPubMed
34.
Tuyama AC, Hong F, Saiman Y, Wang C, Ozkok D, Mosoian A, Chen P, Chen BK, Klotman ME, Bansal MB. Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis. Hepatology. 2010;52(2):612–22.CrossRefPubMedPubMedCentral
35.
Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75.CrossRefPubMed
36.
Wallet MA, Buford TW, Joseph AM, Sankuratri M, Leeuwenburgh C, Pahor M, Manini T, Sleasman JW, Goodenow MM. Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects. BMC Immunol. 2015;16:43.CrossRefPubMedPubMedCentral
37.
Wallet MA, Rodriguez CA, Yin L, Saporta S, Chinratanapisit S, Hou W, Sleasman JW, Goodenow MM. Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS. 2010;24(9):1281–90.CrossRefPubMedPubMedCentral
38.
Dunham RM, Vujkovic-Cvijin I, Yukl SA, Broadhurst MJ, Loke P, Albright RG, Wong JK, Lederman MM, Somsouk M, Hunt PW, et al. Discordance between peripheral and colonic markers of inflammation during suppressive ART. J Acquir Immune Defic Syndr. 2014;65(2):133–41.CrossRefPubMedPubMedCentral
39.
Wada NI, Jacobson LP, Margolick JB, Breen EC, Macatangay B, Penugonda S, Martinez-Maza O, Bream JH. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS. 2015;29(4):463–71.CrossRefPubMedPubMedCentral
40.
Chen J, Shao J, Cai R, Shen Y, Zhang R, Liu L, Qi T, Lu H. Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients. PLoS One. 2014;9(7):e100446.CrossRefPubMedPubMedCentral
41.
Iser DM, Avihingsanon A, Wisedopas N, Thompson AJ, Boyd A, Matthews GV, Locarnini SA, Slavin J, Desmond PV, Lewin SR. Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression. AIDS. 2011;25(2):197–205.CrossRefPubMed
42.
Qin SY, Lu DH, Guo XY, Luo W, Hu BL, Huang XL, Chen M, Wang JX, Ma SJ, Yang XW, et al. A deleterious role for Th9/IL-9 in hepatic fibrogenesis. Sci Rep. 2016;6:18694.CrossRefPubMedPubMedCentral
43.
Sun HQ, Zhang JY, Zhang H, Zou ZS, Wang FS, Jia JH. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis. J Viral Hepat. 2012;19(6):396–403.CrossRefPubMed
44.
Jimenez-Sousa MA, Almansa R, de la Fuente C, Caro-Paton A, Ruiz L, Sanchez-Antolin G, Gonzalez JM, Aller R, Alcaide N, Largo P, et al. Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin. Eur Cytokine Netw. 2010;21(2):84–91.PubMed
45.
Jin-no K, Tanimizu M, Hyodo I, Kurimoto F, Yamashita T. Plasma level of basic fibroblast growth factor increases with progression of chronic liver disease. J Gastroenterol. 1997;32(1):119–21.CrossRefPubMed
46.
Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A, Sebolao B, Tran A, Spelman T, Matthews G, et al. Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy. J Infect Dis. 2014;210(5):745–51.CrossRefPubMed
47.
Wandeler G, Mulenga L, Vinikoor MJ, Kovari H, Battegay M, Calmy A, Cavassini M, Bernasconi E, Schmid P, Bolton-Moore C, et al. Liver fibrosis in treatment-naive HIV-infected and HIV/HBV co-infected patients: Zambia and Switzerland compared. Int J Infect Dis. 2016;51:97–102.CrossRefPubMedPubMedCentral
48.
Bonnard P, Sombie R, Lescure FX, Bougouma A, Guiard-Schmid JB, Poynard T, Cales P, Housset C, Callard P, Le Pendeven C, et al. Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)-infected patients in Burkina Faso. Am J Trop Med Hyg. 2010;82(3):454–8.CrossRefPubMedPubMedCentral
49.
Mbaye PS, Sarr A, Sire J-M, Evra M-L, Ba A, Daveiga J, Diallo A, Fall F, Chartier L, Simon F, et al. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load. PLoS One. 2011;6(7):e22291.CrossRefPubMedPubMedCentral
50.
Abad-Fernandez M, Vallejo A, Hernandez-Novoa B, Diaz L, Gutierrez C, Madrid N, Munoz MA, Moreno S. Correlation between different methods to measure microbial translocation and its association with immune activation in long-term suppressed HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2013;64(2):149–53.CrossRefPubMed
51.
Gonzalez-Quintela A, Alonso M, Campos J, Vizcaino L, Loidi L, Gude F. Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity. PLoS One. 2013;8(1):e54600.CrossRefPubMedPubMedCentral
52.
Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott JH, Hoy J, Cameron PU, Kamarulzaman A, Lewin SR. Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy. AIDS. 2016;30(14):2159–68.CrossRefPubMedPubMedCentral
Metadata
Title
HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa
Authors
Tongai Gibson Maponga
Monique I. Andersson
Christoffel J. van Rensburg
Joop E. Arends
Jantjie Taljaard
Wolfgang Preiser
Richard H. Glashoff
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3115-8

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue

Research article

Dengue score as a diagnostic predictor for pleural effusion and/or ascites: external validation and clinical application

Research article

Validation of blood culture gram staining for the detection of Staphylococcus aureus by the ‘oozing sign’ surrounding clustered gram-positive cocci: a prospective observational study

Research article

Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model

Research article

Incubation period of typhoidal salmonellosis: a systematic review and meta-analysis of outbreaks and experimental studies occurring over the last century

Research article

Persistent candidemia in very low birth weight neonates: risk factors and clinical significance

Research article

Molecular epidemiology and clinical features of hand, foot and mouth disease in northern Thailand in 2016: a prospective cohort study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits