Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis C.
ABSTRACT Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis. Obesity is accompanied by a low-grade, chronic inflammatory response that may contribute to pathogenesis of obesity-related comorbidities. To assess whether obesity and steatosis potentiate expression of inflammatory markers in chronic HCV, serum protein and hepatic messenger RNA (mRNA) levels of c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured in 171 patients with chronic HCV. The relationships of body mass index, steatosis, histological features of inflammation and fibrosis with serum and hepatic levels of these factors were determined. In comparison with lean patients, overweight and obese subjects had increased circulating (P < 0.001) and hepatic (P = 0.003) CRP, and there was a significant correlation between serum protein and hepatic CRP mRNA levels (r(s)= 0.51, P < 0.001). Obesity (P = 0.001) and steatosis (P < 0.001) were associated with increased circulating but not hepatic IL-6, and a weak correlation was seen between serum protein and hepatic IL-6 mRNA levels (r(s)= 0.29, P = 0.003). An independent relationship was seen between hepatic TNF-alpha mRNA levels and higher total inflammatory score (P < 0.001) and stage of fibrosis (P = 0.037). Subjects with HCV genotype 3 had lower hepatic TNF-alpha mRNA levels compared with subjects with genotype 1 (P = 0.017), but there was no relationship between serum TNF-alpha protein and hepatic TNF-alpha mRNA levels. CONCLUSION: In patients with chronic HCV, obesity and steatosis are associated with increased expression of selected inflammatory markers; however, circulating levels of IL-6 and TNF-alpha do not reflect hepatic expression. Hepatic TNF-alpha was associated with both increased inflammatory activity and hepatic fibrosis, providing support for the key role of this pro-inflammatory cytokine in liver injury in chronic HCV.
- SourceAvailable from: Ganji Purnachandra Nagaraju[Show abstract] [Hide abstract]
ABSTRACT: Adiponectin is produced in the white adipose tissue and is known to have anti-metabolic and anti-inflammatory properties. Serum/plasma adiponectin levels depend on diet, physical activity, and inheritance. Epidemiologic observations suggest a potential link between obesity and gastrointestinal malignancies. Low levels of adiponectin, which are known to occur in obesity, may contribute to the high incidence of cancer in this population. This review discusses the biochemical and molecular evidence regarding the relationship between adiponectin and gastrointestinal carcinogenesis and provides several future perspectives on the role of adiponectin as a target for prevention and therapy.Cytokine & Growth Factor Reviews 06/2014; · 6.54 Impact Factor
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ABSTRACT: To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism).PLoS ONE 07/2014; 9(7):e101760. · 3.53 Impact Factor
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ABSTRACT: In chronic hepatitis C virus infection (CHC), expression of suppressor of cytokine signaling-3 (SOCS3) has been shown to be associated with obesity and non-response to antiviral therapy. In this study, we aimed to determine the effect of SOCS3 induction on the cytokine response in patients receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy. Peripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein SOCS3 expression. Immunological assays were employed to examine cytokine production. There was increased expression of SOCS3 in PBMC of non-responders at week 12 of therapy, when compared to treatment responders (p=0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r=0.54; p=0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV-specific IFN-γ production in enzyme-linked immunosorbent spot (ELISpot) assays (p=0.01), and reduced ex-vivo production of the anti-HCV effector cytokines interleukin (IL)-2 and tumour necrosis factor (TNF)-α (p=0.01 and p=0.04, respectively). Analysis of serum cytokine levels revealed higher levels of IL-6 at week 12 in the high SOCS3 expression group (p=0.02) while IL-6 levels correlated with SOCS3 expression in the entire cohort (p=0.04). Ex-vivo studies confirmed that IL-6 induced SOCS3, and neutralization of IL-6 reduced levels of SOCS3. In subjects with increased BMI and non-response to antiviral therapy, the IL-6/SOCS3 axis appears to play a crucial role in altering the anti-HCV-cytokine response associated with antiviral therapy. This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 02/2014; · 4.41 Impact Factor