Sexually Dimorphic Differences in the Regulation of Pancreatic Hormones and Growth Factors on Liver Metabolism in Patients with Cirrhosis

Abstract Hepatocyte growth factor (HGF) exerts potent mitogenic effects in multiple tissues, whereas epidermal growth factor (EGF) functions as a molecular integration point for diverse signaling stimuli. The HGF–Met system plays an active role in hepatic metabolism. In this observational study, we aimed to identify correlations among serum levels of HGF and EGF, insulin, glucagon, and major serum lipids in patients with cirrhosis, with particular attention to sex-related differences. Serum concentrations of HGF, EGF, insulin, glucagon, major lipids, and nitrogen-related metabolites were measured through analytical methods to assess the relationships among these parameters in patients with cirrhosis and healthy controls. We observed clear differences in glucose, insulin, and glucagon regulation between healthy men and women, along with opposing associations with growth factors, potentially reflecting the distinct modulatory effects of sex hormones. At the onset of liver fibrosis/cirrhosis, most of the correlations observed in healthy individuals were lost, and sex-related differences became markedly attenuated. In addition, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia appeared to influence circulating growth factor and hormone levels. In conclusion, our findings support a role for HGF and EGF in the regulation of serum glucose, lipid and nitrogen metabolism, as well as in the modulation of insulin and glucagon levels, in a sex-dependent manner. These relationships were particularly evident in patients with liver fibrosis/cirrhosis, in whom impaired cellular growth or repair mechanisms are associated with metabolic dysregulation. Collectively, these observations suggest that growth factors may contribute to the physiopathology of chronic liver disease.