Characterization of serum activin-A and follistatin and their relation to virological and histological determinants in chronic viral hepatitis.
METHODS
Hepatocyte proliferation in viral hepatitis is regulated by a number of growth factors. Activin-A inhibits hepatocyte DNA synthesis while follistatin, a potent activin-A antagonist, promotes liver regeneration. We report the first study of activin-A and follistatin in human viral hepatitis. Sera from 15 normal subjects, 22 hepatitis B and 47 hepatitis C patients were analysed for activin-A and follistatin and correlated with serological and histological markers of liver injury and with specific immunohistochemistry.


RESULTS
All groups showed immunoreactivity for activin with hepatocyte localisation. Serum activin-A was significantly increased in viral hepatitis patients compared to controls, was greater in hepatitis B compared to hepatitis C, and correlated with serum aminotransferase and hepatitis B viral replication. A concurrent rise in serum follistatin was not observed in either group, but serum follistatin correlated inversely with hepatitis B DNA levels. Although hepatocyte apoptosis in hepatitis C and proliferation in both groups was significantly elevated compared to controls, there was no correlation with serum activin-A or follistatin.


CONCLUSIONS
Activin-A and follistatin are constitutively expressed in human liver and serum concentrations are increased in viral hepatitis. Dysregulation of the activin/follistatin axis may be linked to hepatitis B replication but does not correlate with hepatocyte apoptosis.
Patella
S
S
Department of Medicine, Centre for Inflammatory Diseases, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
Phillips
D J
DJ
de Kretser
D M
DM
Evans
L W
LW
Groome
N P
NP
Sievert
W
W
D028341:Activins; D000328:Adult; D017209:Apoptosis; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007265:Inhibins / Q000097:blood* / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration
D038681:Follistatin; D006023:Glycoproteins; D028341:Activins; D007265:Inhibins