Increased IGF-1: IGFBP-3 ratio in patients with hepatocellular carcinoma

BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors. AIM: The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 ± 10 and 65 ± 7 vs. 185 ± 6.4 μg/l, P < 0.001) and IGFBP-3 levels (1225 ± 113 and 984 ± 67 vs. 3017 ± 80 μg/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels In patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 ± 2 vs. 57 ± 2 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 ± 0.05 vs. 0.41 ± 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 ± 5.6 vs. 42 ± 6.2 μg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 ± 81 vs. 679 ± 83 μg/l). CONCLUSIONS: Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure