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

Abstract

BackgroundCo-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.MethodsWe 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.ResultsHBV/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.DiscussionHighly-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.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3115-8) contains supplementary material, which is available to authorized users.

Analysis of different levels of viral suppression in HIV-1 patients after antiviral treatment

“…In our study, CD4 cell counts baseline under 500 n/µL and co-infected with HBV were independent risk factors for high HIV-1 replication. These were consistent with previous studies [19][20] . Young age and test & treat were independent protective factors for viral suppression.…”

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

“…[306][307][308] CD38 is the third NAD + -consuming enzyme that is upregulated in response to a number of viral infections. [309][310][311][312] CD38 is under the transcriptional control of RSV-induced IFNs. The CD38generated cADPR, in turn, augments the IFNs-induced ISGs and NF-κB-mediated inflammation, leading to the antiviral hyperinflammation response.…”

Treatment advantage in HBV/HIV coinfection compared to HBV monoinfection in a South African cohort

“…A previous report also documents elevated rates of severe fibrosis in HBV monoinfected compared to their HBV/HIV coinfected counterparts, 32 although this observation is not consistent between settings. 4 The reduced liver disease we observed in coinfected individuals highlights the positive impact of wider treatment access, which whilst prescribed to treat HIV, is also inadvertently suppressing HBV.…”