Impaired Follistatin Secretion in Cirrhosis

Context: Follistatin is a liver-derived inhibitor of the muscle-growth inhibitor myostatin. Reduction in acute follistatin release may help explain muscle loss in liver cirrhosis. Objective: The study aimed to investigate the capacity of acute follistatin release in patients with liver cirrhosis compared to healthy control participants. Design, Setting, and Participants: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon/somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis patients with eight healthy control participants. Patients and controls received 1-hour glucagon/somatostatin and saline infusions on 2 separate days. Main Outcome Measure: Follistatin was measured during and 5 hours after termination of infusions. Results: The peak follistatin change was significantly decreased in patients with liver cirrhosis compared to healthy control participants (1.9 (interquartile range, 1.4-2.5) versus 3.6 (interquartile range, 3.0-4.0), respectively; P = .003). Patients with liver cirrhosis demonstrated significantly decreased amounts of appendicular lean mass compared to healthy controls (27.6 +/- 3.8 vs 34.5 +/- 2.9%, respectively; P = .001). Conclusions: Patients with cirrhosis show impaired capacity to acutely secrete follistatin. The decrease in acute follistatin release may contribute to the loss of muscle mass in liver cirrhosis.