The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease

Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.