Abstract
Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL) or had chronic HCV infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.
Highlights
Hepatic disease is a leading cause of significant morbidity and death among HIV infected persons in the US; 15–30% of HIV-infected individuals are coinfected with hepatitis C virus (HCV)[1,2,3,4] and this is associated with metabolic and cardiovascular complications in addition to other inflammation induced comorbidities
IP-10, an interferon-induced protein that has been implicated in liver fibrosis [34,35] and lower ability to clear infection [36], was elevated in HCV RNA+ women even among those women with suppressed HIV replication
The very high IP-10 levels seen in the women with uncontrolled HIV replication dominate the relatively weaker IP-10 induction driven by HCV RNA
Summary
Hepatic disease is a leading cause of significant morbidity and death among HIV infected persons in the US; 15–30% of HIV-infected individuals are coinfected with hepatitis C virus (HCV)[1,2,3,4] and this is associated with metabolic and cardiovascular complications in addition to other inflammation induced comorbidities. HIV and HCV infections increase expression of inflammatory cytokines and chemokines [5,6,7]. These factors have been found to be associated with long-term morbidity in HIV infection or chronic hepatitis [7,8,9,10,11]. HIV-induced immune perturbation, including CD4 cell loss, generalized inflammation and trafficking of activated immune cells to the liver in HCV infection likely results in greater tissue damage and fibrosis [13,14]
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