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Background/Aims: TNFαinduces insulin resistance and promoter polymorphisms of TNFαgene affect the release of this cytokine, implicated in the pathogenesis of HCV-related diabetes and fatty liver. The aim was to define whether in patients with HCV chronic hepatitis TNFαgenotype influences TNFαactivity, insulin resistance, and the severity of the disease. Methods: 186 patients, 65%with steat osis, 17%with diabetes. TNFαand sTNFR2 were determined by ELISA, insulin resis tance by HOMA-R index and TNFα-238, -308, and -863 polymorphisms by restric tion analysis. Results: TNFα, sTNFR2, and insulin resistance were higher in pat ients than in 89 controls. TNFαpathway activity was correlated with LDL cholest erol, steatosis, and insulin resistance, which, in turn, was correlated with the severity of liver damage. Patients subdivided according to TNFαgenotype signif icantly differed for TNFαrelease, insulin sensitivity and the prevalence of cir rhosis. The -308 and -238 TNFαpolymorphisms, characterized by increased promo ter activity, were associated with higher TNFαactivity, insulin resistance and severity of the disease, whereas the -863 polymorphism, characterized by reduce d promoter activity, with lower TNFαactivity, and higher insulin sensitivity. C onclusions: TNFαgenotype modulates the activity of the TNFαpathway, influences insulin sensitivity and the severity of HCV chronic hepatitis.
Background / Aims: TNFαinduces insulin resistance and promoter polymorphisms of TNFαgene affect the release of this cytokine, implicated in the pathogenesis of HCV-related diabetes and fatty liver. The aim was to define whether in patients with HCV chronic hepatitis TNFαgenotype influences TNFαactivity, insulin resistance , and the severity of the disease. Methods: 186 patients, 65% with steatosis, 17% with diabetes. TNFαand sTNFR2 were determined by ELISA, insulin resisance by HOMA-R index and TNFα-238, -308, and -863 Results: TNFα, sTNFR2, and insulin resistance were higher in pat ients than in 89 controls. TNFαpathway activity was correlated with LDL cholest erol, steatosis, and insulin resistance, which, in, turn, was correlated with the severity of liver damage. Patients subdivided according to TNFα genotype signif icantly differed for TNFα release, insulin sensitivity and the prevalence of cir rhosis. The -308 and -238 TNFα polymorphisms ms, characterized by increased promo activity, were associated with higher TNFα activity, insulin resistance and severity of the disease, but the -863 polymorphism, characterized by reduced d promoter activity, with lower TNFα activity, and higher insulin sensitivity. C onclusions: TNFαgenotype modulates the activity of the TNFαpathway, influences insulin sensitivity and the severity of HCV chronic hepatitis.