Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with HCV genotype 1

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance. We tested serum levels of RB4 to assess its link with steatosis in patients with genotype 1 (G1) chronic hepatitis C (CHC) or non-alcoholic fatty liver disease (NAFLD). Non-diabetic patients with CHC (n=143) or NAFLD (n=37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including insulin resistance by the homeostasis model assessment (HOMA). Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe ≥30%. Thirty non-diabetic, non-obese blood donors served as controls. RBP4 levels were measured by a human competitive ELISA kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3±9.3 µg/L vs 36.8±17.6 p=0.47), and both significantly higher than in controls (28.9±12.1; p=0.02 and p=0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1±19.7 vs 35.2±9.3; p=0.04). By linear regression, RBP4 was independently linked to steatosis only (p= 0.008) in CHC, and to elevated BMI (p= 0.01) and low grading (p= 0.04) in NAFLD. By linear regression, steatosis was independently linked to HOMA-score (p= 0.03) and high RBP4 (p= 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (OR 1.045; 95%CI 1.020-1.070; p=0.0004), while waist circumference was associated with moderate-severe steatosis in NAFLD (OR 1.095; 95%CI 1.007-1.192; p=0.03). We conclude that in non-diabetic, non-obese patients with G1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to insulin resistance.