Role of Cytokines in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

A number of factors are linked with non-alcoholic fatty liver diseases (NAFLD), a condition that ranges from clinically benign fatty liver to its more severe form, non alcoholic steatohepatitis (NASH). In this study, we evaluated the role of cytokines secreted from adipose tissue in the pathogenesis and progression of NAFLD. We also compared anthropometric profile, lipid profile and insulin resistance data in 105 NAFLD patients with 77 normal subjects. These subjects showed a normal serum albumin level, prothrombin time and renal function but elevated aminotransferases. Predisposing factors were diabetes mellitus (35%), overweight (56%) and hyperlipidemia (44%). Insulin resistance (IR), determined by homeostasis model assessment (HOMA) was confirmed in 70% patients with NAFLD and 42% patients fulfilled the minimum criteria for insulin resistance syndrome (IRS). NAFLD patients showed elevated levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, and interleukin (IL)6, while anti-inflammatory cytokines IL-4 level decreased and IL-10 level remain unchanged; however, TGF-b1 level elevated significantly compared to normal subjects. While insulin level and HOMA-IR both were significantly positively correlated with BMI, waist-to-hip ratio, total cholesterol, VLDL-cholesterol, triglyceride and TGF-beta 1; glucose, IL-6 and TNF-alpha levels were significantly positively correlated with HOMA-IR only. In conclusion, proinflammatory cytokines play an important link between metabolic and liver disorders in the fat accumulation, and thereby cause IR, inflammation and liver fibrosis.