Fibrosis is associated with adiponectin resistance in chronic hepatitis C virus infection

Background Chronic hepatitis C virus (HCV) infection is frequently associated with insulin resistance which has been suggested to promote fibrotic progression. Adiponectin, an adipocyte-derived insulin-sensitizing hormone, might play a protective role against hepatic fibrosis. Materials and methods This observational case-control study investigated the adiponectin status in insulin resistant, nondiabetic, chronic HCV-infected patients (n=54; 13 women, 41 men) compared with age-, sex- and BMI-matched healthy controls. Liver biopsies from patients with chronic HCV hepatitis were analysed for the adiponectin and adiponectin receptors (ADIPOR) 1 and 2 mRNA and protein expressions. Results Serum adiponectin levels were higher in patients with chronic HCV hepatitis than in healthy controls (12·1±4·7 vs. 9·5±4·4mgL ^-1 in men, P=0·01; 18·2±4·4 vs. 13·6±5·3mgL ^-1 in women, P=0·02). BMI, HDL cholesterol and triglycerides levels correlated with adiponectin levels both in patients and in controls, while no correlation with glucose, insulin and HOMA-IR values could be detected. Nonetheless, insulin resistance was predictive of steatosis and fibrosis in chronic HCV-infected patients. Interestingly, patients with none or mild fibrosis showed serum adiponectin levels similar to those in healthy controls, while hyperadiponectinemia was associated with moderate to severe stages of fibrosis. Hyperadiponectinemia was unlikely sustained by liver production as hepatocytes did not express the protein. ADIPOR1 mRNA, but not ADIPOR2 levels, was reduced in chronic HCV hepatitis. The reduced ADIPOR1 expression was confirmed by immunohistochemistry. Conclusions In patients with chronic HCV hepatitis, fibrosis was associated with hyperadiponectinemia. Chronic HCV-infected hepatocytes showed reduced ADIPOR1 expression, suggesting a pattern of adiponectin resistance.