Intrahepatic interleukin 10 expression modulates fibrinogenesis during chronic HCV infection.

INTRODUCTION: Liver fibrosis is a result of continuous damage to the liver combined with accumulation of the extracellular matrix and is characteristic of most chronic liver diseases such as hepatitis C virus (HCV) infection. METHODS: This study evaluated interleukin 10 (IL10) expression in the liver and plasma of 45 HCV patients and its association with the pathogenesis and progression of liver fibrosis. The expression of transforming growth factor beta (TGFB1) was also assessed. Patients were divided into three groups according to the METAVIR classification (F0-F1, F2 and F3-F4); there was also a control group (n = 8). RESULTS: In the control group, high intrahepatic IL10 mRNA expression showed a positive association with F0-F1 fibrosis, no inflammation, low concentrations of liver enzymes and a high viral load; conversely, low intrahepatic IL10 mRNA expression showed a negative association with fibrosis progression. Intrahepatic TGFB1 mRNA expression was greater in the HCV group than in the control group, and regarding different disease phases, its expression increased as fibrosis evolved to more severe forms. CONCLUSION: Intrahepatic IL10 mRNA expression decreases with persistent fibrosis, probably due to the production of TGF-ß1, a potent antimitotic and fibrogenic cytokine. IL10 restricts and decreases the immune response and limits the fibrogenic response; however, a decrease in IL10 favors persistent inflammatory infiltrate, resulting in severe fibrosis.

Polymorphisms in the TGFB1 and FOXP3 genes are associated with the presence of antinuclear antibodies in chronic hepatitis C.

Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the FOXP3, IFNG, IL6, IL8, IL10, MBL2, CRP, TGFΒ1 and TNFA genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the FOXP3 rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the TGFΒ1 rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.