Transforming growth factor-beta 1, activin and follistatin in patients with hepatocellular carcinoma and patients with alcoholic cirrhosis

Abstract

Background: Transforming growth factor-beta 1 (TGF-β1) exerts an inhibitory effect on DNA synthesis in hepatocytes. Activin, through different mechanisms, also exhibits an apoptotic effect on hepatocytes. Follistatin antagonizes the actions of activin. Methods: Patients with hepatocellular carcinoma (HCC, n = 20), patients with alcoholic cirrhosis (n = 12), patients with cirrhosis due to other causes (n = 5) and normal controls (n = 19) were studied. TGF-β1, activin and follistatin concentrations in blood and ascites were measured by ELISA. Results: All three groups of patients had significantly higher serum levels of total TGF-β1, activin and follistatin compared to those of controls. In patients with HCC, the total TGF-β1 level correlated negatively with tumour size (r = -0.644, P = 0.001). The activin level correlated with alkaline phosphatase (ALP) level (r= 0.374, P = 0.046). The follistatin level correlated with the ALP level (r = 0.404, P = 0.026), and the glutamyl transpeptidase level (r = 0.457, P = 0.01). In patients with alcoholic cirrhosis, serum activin correlated with the Child-Pugh score (r = 0.601, P = 0.01). The levels of the cytokines in ascites (n = 16) did not correlate with the corresponding levels in serum. Conclusions: Serum levels of total TGF-β1, activin and follistatin were elevated in patients with hepatocellular carcinoma and in patients with alcoholic cirrhosis. Apoptosis of tumour cells may be reduced by a subsequent decrease in serum TGF-β1 levels when the tumours expand in size. Activin and follistatin were associated with tumour activity, as both correlated with ALP and/or GGT levels. Further studies are required to define the exact relationships between these cytokines, the dynamics of tumour growth and their significance in cirrhosis.