Transforming growth factor-beta 1, activin and follistatin in patients with hepatocellular carcinoma and patients with alcoholic cirrhosis.
BACKGROUND
Transforming growth factor-beta 1 (TGF-beta1) 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-beta1, 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-beta1, activin and follistatin compared to those of controls. In patients with HCC, the total TGF-beta1 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-beta1, 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-beta1 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.
Yuen
M F
MF
Institute of Liver Studies, Guy's, King's and St Thomas' School of Medicine, London, UK. yuenmf@netvigator.com
Norris
S
S
Evans
L W
LW
Langley
P G
PG
Hughes
R D
RD
D028341:Activins / Q000097:blood*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D038681:Follistatin; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000097:blood*
D038681:Follistatin; D016212:Transforming Growth Factor beta; D028341:Activins