Characterization of serum activin-A and follistatin and their relation to virological and histological determinants in chronic viral hepatitis

Background/Methods: Hepatocyte proliferation in viral hepatitis is regulate d by a number of growth factors. Activin-A inhibits hepatocyte DNA synthesi s while follistatin, a potent activin-A antagonist, promotes liver regenera tion. 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 s erological and histological markers of liver injury and with specific immun ohistochemistry. Results: All groups showed immunoreactivity for activin with hepatocyte loc alisation. Serum activin-A was significantly increased in viral hepatitis p atients compared to controls, was greater in hepatitis B compared to hepati tis C, and correlated with serum aminotransferase and hepatitis B viral rep lication. A concurrent rise in serum follistatin was not observed in either group, but serum follistatin correlated inversely with hepatitis B DNA lev els. Although hepatocyte apoptosis in hepatitis C and proliferation in both groups was significantly elevated compared to controls, there was no corre lation with serum activin-A or follistatin. Conclusions: Activin-A and follistatin are constitutively expressed in huma n liver and serum concentrations are increased in viral hepatitis. Dysregul ation of the activin/follistatin axis may be linked to hepatitis B replicat ion but does not correlate with hepatocyte apoptosis. (C) 2001 European Ass ociation for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.