Serum follistatin levels predict the extent of liver regeneration after hepatectomy in human and rat models

Abstract

Abstract Introduction: Extensive hepatectomy in an attempt to obtain cure for large liver tumors may cause liver failure. Therefore, a marker to predict an adequate regeneration is needed. We have recently published that activin, a member of TGF-beta superfamily, is one of the key factors that inhibits liver regeneration in vivo using adenovirus-mediated overexpression of follistatin, an activin antagonist. These results lead us to investigate the usefulness of endogenous follistatin levels in a clinical setting. Here, we demonstrate serum follistatin levels predict the outcome after hepatectomy in both animal and human models. Methods: Rats underwent either 95% (mortal group) or 90% (survival group) removal of the liver. Serum follistatin levels were measured by ELISA serially after hepatectomy in both rats and patients with liver cancer. The liver volume was measured by CT 28 days after hepatectomy. Results: There was a significant difference between mortal and survival model in bilirubin levels 48 hours after surgery, but not in the other liver function tests. On the other hand, follistatin levels were significantly elevated only in the mortal group 24 hours after surgery. Similar remarkable elevation of follistatin level was observed in a patient who died from post-hepatectomy liver failure. Furthermore, follistatin levels decreased significantly after hepatectomy and the levels at POD 1 and 3 correlated inversely with the degree of increase in the volume of the remaining liver in humans. Conclusions: Serum follistatin levels represent a novel early detection marker for liver failure after hepatectomy, and it decreases in proportion to the degree of liver regeneration.