Myostatin as a fibroblast activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma.

AIM In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of NAFLD-HCC patients without cirrhosis and on the progression of liver fibrosis. METHODS Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. RESULTS The median age was 67.4 years, the median L3 SMI was 44.4 cm2 / m2 , and the median BMI was 23.4 kg/ m2 . Eighty-two (35.0%) patients had sarcopenia (L3 SMI: men <42, women <38 cm2 /m2 ). The etiologies of liver disease were hepatitis B virus (HBV) (n=61), hepatitis C virus (HCV) (n=86), and non-B non-C hepatitis (NBNC) (n=87) including NAFLD (n=74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in the patients with no sarcopenia (n=152). In patients without advanced liver fibrosis (Fibrosis stage, 0-2) (n=58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin. CONCLUSIONS In NAFLD-HCC patients without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts, and stimulated collagen production. This article is protected by copyright. All rights reserved.