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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Infectious Diseases 1/2018

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

BMC Infectious Diseases > Ausgabe 1/2018
Tongai Gibson Maponga, Monique I. Andersson, Christoffel J. van Rensburg, Joop E. Arends, Jantjie Taljaard, Wolfgang Preiser, Richard H. Glashoff
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12879-018-3115-8) contains supplementary material, which is available to authorized users.
Data presented previously in part at the 21st International AIDS Conference (AIDS 2016) Durban, South Africa, 18-22 July 2016 and as part of Tongai Maponga’s PhD thesis deposited in the SUNScholar repository at Stellenbosch University.



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.


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.


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.


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.
Additional file 1: Table S1. Serum LPB concentration according to patient group (μg/ml). Table S2. Proportions of fibrosis scores according to the HBV genotype. Table S3. Multiple correlation analysis of all patients ungrouped. Statistically significant correlations appear in red font. Figure S1. Gating strategy for Immune Activation panel. Plot A shows the singlet population gating while Plot B represents the SSC against FSC plot indicating the position of the singlet cells of the lymphocyte population. Plot C shows the lymphocyte population as shown by less complexity (SS) and intense staining for CD45-KO in a plot of side scatter against CD45-KO. Plot D shows the CD3+ population (Gate G) as gated from Gate F shown in Plot C. Using colour precedence and back gating, Plot D also shows the non-lymphocyte population (red colour) that is included within gate F based on use of complexity (SS INT) and staining for CD45. Picture E shows the CD4+ in the blue colour (gate H) and the CD8+ lymphocytes in the magenta colour (gate I). Plot F shows the CD8+ population staining for CD38-PE and HLA-DR-APC gated from gate I. The gate placement was based on defined fluorescence minus one (FMO) settings. Figure S2. Scatter plot of % CD8/CD38+/HLA-DR+ in the co-infected group. The plot only includes HBV/HIV co-infected patients. All patients with undetectable HIV viral load are assigned values of zero and appear on the y-axis as dots corresponding with the percentage expression CD8/CD38+/HLA-DR. Frequency of HBV genotypes according to HBV and HIV infection status. Among the 13 co-infected patients whose HBV was successfully sequenced, 8 (62%) were infected with HBV genotype A, 3 (23%) with D and 2 had HBV genotype E (15%). The distribution of genotypes among the HBV mono-infected patients was- 16/29 (55%) A, 11/29 (38%) D and 2/29 (7%) E. The red columns represent HBV genotype A, green is for genotype D and the blue corresponds to genotype E. Genotyping was frequently more successful in the HBV mono-infected group compared to the co-infected group. (DOCX 475 kb)
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