Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus co-infection: Infiltrating cells, cytokines, and influence of HAART
ABSTRACT Liver disease is more progressive in HIV/hepatitis C virus (HCV) co-infection than in HCV infection alone. This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines.
Using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) we studied intrahepatic messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV-mono-infected and 40 HIV/HCV-co-infected patients.
Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/microl), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3epsilon, TCRalpha, CD8alpha and CD8beta suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-gamma), regulated upon activation, normal T-cell expressed and secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and interferon-inducible protein 10 (CXCL10) were significantly higher in HIV-positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two groups. All changes were less pronounced in the subgroup of HIV-positive patients receiving antiretroviral treatment (HAART) than in untreated HIV-positive patients.
The accelerated liver disease observed in HIV/HCV-co-infected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines.
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- "Gonzalez et al. assessed cytokine levels in liver biopsies on liver samples from HCV/HIV co-infected and HCV mono-infected patients. They measured IFN-γ, Tumor Necrosis Factor (TNF)-α, Transforming Growth Factor (TGF)-β1, interleukin (IL)-4, IL-10, IL-12p35 and IL-12p40 mRNA levels by real-time PCR performed on liver biopsies of HCV mono-infected (n=19) and HCV/HIV co-infected (n=24) patients (Table 1).59-67 The results showed that the co-infected patients had decreased intrahepatic mRNA levels of IFN-γ, IL-4 and IL-12p35 compared with mono-infected patients while IL-10 was increased. "
ABSTRACT: Around 33 million people worldwide are living with Human Immunodeficiency Virus (HIV) infection, and approximately 20-30% of HIV-infected individuals are also infected with Hepatitis C virus (HCV). The main form of HCV transmission is via the blood borne route; high rates of co-infection are found in intravenous drug users with HCV prevalence rates as high as 90%. Introduction of effective antiretroviral therapy (ART) has led to a significant decline in HIV-related morbidity, but at the same time the incidence of HCV related liver disease is increasing in the co-infected population. Meta analysis has revealed that individuals who are co-infected with HIV/HCV harbor three times greater risk of progression to liver disease than those infected with HCV alone. Increased risk of progression to Acquired Immunodeficiency Syndrome (AIDS) and AIDS-related deaths is shown among the co-infected patients by some studies, suggesting that HCV infection may accelerate the clinical course of HIV infection. HCV may also affect the incidence of liver toxicity associated with ART, affecting the management of HIV infection. There is a lack of optimal therapeutic approaches to treat HCV infection in HIV co-infected patients. This review discusses recent literature pertaining HIV/HCV co-infection, in addition to providing a snapshot of impact of co-infection on human genome at the level of gene expression and its regulation by microRNAs (miRNAs).Infectious disease reports 06/2013; 5(Suppl 1):e7. DOI:10.4081/idr.2013.s1.e7
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- "Regarding the association between HIV-RNA viral load and plasma CXCL10 level, previous studies in HIV-monoinfected patients on HAART have reported higher CXCL10 levels in non-responders than in HAART responders (undetectable plasma HIV-RNA) . In fact, HAART also improves T-cell number and its function, which might result in a significant decrease of immune activation on Tcell , and inflammatory responses in liver biopsy . Insulin resistance and type-2 diabetes, common comorbidities in CHC patients, are proinflammatory conditions, which are associated with steatosis, advanced fibrosis and poor response to HCV antiviral therapy  . "
ABSTRACT: CXCL10 may contribute to the host immune response against the hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral therapy. The aim of our study was to analyze the relationship among virological, immunological, and clinical characteristics with plasma CXCL10 levels in human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 144 patients. CXCL10 and insulin were measured using an immunoassay kit. The degree of insulin resistance was estimated for each patient using the homeostatic model assessment (HOMA) method. Insulin resistance was defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were calculated. The variables associated with log(10) CXCL10 levels by univariate analysis were age (b=0.013; p=0.023), prior AIDS-defining condition (b=0.127; p=0.045), detectable plasma HIV viral load (b=0.092; p=0.006), log(10) HOMA (b=0.216; p=0.002), HCV-genotype 1 (b=0.114; p=0.071), and liver fibrosis assessed by all non-invasive indexes (log(10) APRI (b=0.296; p=0.001), log(10) FIB-4 (b=0.436; p<0.001), log(10) Forns index (b=0.591; p<0.001), log(10) HGM1 (b=0.351; p=0.021), and log(10) HGM2 (b=0.215; p=0.018)). However, in multivariate analysis, CXCL10 levels were only associated with HOMA, detectable plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square=0.235; p<0.001). Plasma CXCL10 levels were influenced by several characteristics of patients related to HIV and HCV infections, insulin resistance, and liver fibrosis, indicating that CXCL10 may play an important role in the pathogenesis of both HCV and HIV infections.Cytokine 12/2011; 57(1):25-9. DOI:10.1016/j.cyto.2011.10.020 · 2.87 Impact Factor
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- "Coinfection increases apoptosis of hepatocytes through a Fas/FasL pathway that could account for accelerated liver disease [17, 18]. Accumulation of cytotoxic CD8 T cells in the liver that increases inflammatory mediators in co-infected compared to HCV-monoinfected patients may also lead to increased tissue damage in co-infected patients [39, 40]. New evidence shows HIV-specific CD8 T cells accumulate in the liver in co-infection and produce TNF-α, which is associated with liver fibrosis [18, 41]. "
ABSTRACT: World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies.Current HIV/AIDS Reports 03/2011; 8(1):12-22. DOI:10.1007/s11904-010-0071-3