Serum hepatocyte growth factor levels in liver diseases: Clinical implications

Although recent studies have shown that hepatocyte growth factor (HGF) is a potent mitogen in vivo, the significance of serum HGF in liver diseases remains unclear. To clarify clinical significance of serum HGF in liver diseases, serum HGF was measured in 127 patients with liver diseases and in 200 healthy individuals, using a highly sensitive immunoradiometric assay (IRMA). This assay is specific for HGF and is sensitive enough to detect 0.1 ng/mL of HGF. Mean values for serum HGF in acute hepatitis (AH), chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), primary biliary cirrhosis (PBC), fulminant hepatic failure (FHF), and normal controls were 0.45, 0.40, 1.05,1.06, 0.44, 16.40, and 0.27 ng/mL, respectively. Serum HGF levels in these diseases were significantly increased compared with those in the controls (P < .001), and exhibited a positive correlation with total bilirubin, indocyanine green (ICG) test (R15), asparate aminotransferase (AST), and a negative correlation with albumin and prothrombin time (P < .001). Cirrhotic patients with modified Child class C had higher levels of serum HGF than those graded as modified Child class A or B (P < .001). In CH, serum HGF levels were significantly related to the histological activity index (HAI) score (P < .002). Seven patients with HCC who underwent transcatheter arterial embolization (TAE) exhibited a gradual increase in serum HGF levels up to day 4 after treatment; these higher levels were maintained until day 7, although AST reached a peak on day 2 and then decreased gradually. During clinical courses of patients with AH and CH, serum HGF was increased immediately after elevations of aminotransferases, and decreased as clinical symptoms improved. Serum HGF levels in survivors with FHF or AH were decreased during the illness (P = .0156), whereas serum HGF levels in nonsurvivors with FHF were increased. These findings suggest that serum HGF reflects the degree of liver dysfunction in chronic hepatic failure, and that serial measurement of serum HGF levels in acute hepatic injury serves as a prognostic factor.