Resistin serum levels are associated with insulin resistance, disease severity, clinical complications, and prognosis in patients with chronic liver diseases

OBJECTIVES: Hyperinsulinemia and insulin resistance are present in nearly all patients with liver cirrhosis. Resistin, a mainly adipose-derived peptide hormone, reduces insulin sensitivity in adipocytes, skeletal muscles, and hepatocytes. In experimental cirrhosis models, resistin expression is upregulated. We aimed to evaluate the potential clinical value of resistin in chronic liver diseases (CLD). METHODS: Serum resistin was measured in 82 non-diabetic CLD patients during evaluation for potential liver transplantation and 76 age- and sex-matched healthy controls. Patients were followed for 6 yr. RESULTS: Resistin serum levels were significantly elevated in patients with liver cirrhosis compared with healthy controls (p < 0.001). Resistin increased with stage of liver cirrhosis as defined by Child-Pugh or model for end-stage liver disease (MELD) score. Serum resistin correlated with insulin secretion (C-peptide, p < 0.001) and inversely with insulin sensitivity (HOMA-index, p = 0.008) in CLD patients. Resistin also correlated inversely with markers of hepatic biosynthetic capacity and positively with markers of inflammation such as tumor necrosis factor alpha (TNF-alpha) or C-reactive protein (CRP), as well as with clinical complications, e.g., portal hypertension. Patients with elevated resistin had increased mortality in 6-yr-survival (p = 0.005, Cox regression model). CONCLUSION: Resistin offers novel application potential as a clinical biomarker in the assessment of liver cirrhosis. Elevated resistin may contribute to insulin resistance in advanced liver dysfunction.