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Myostatin as a fibroblast‐activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma
Author(s) -
Yoshio Sachiyo,
Shimagaki Tomonari,
Hashida Ryuki,
Kawaguchi Takumi,
Tsutsui Yuriko,
Sakamoto Yuzuru,
Yoshida Yuichi,
Kawai Hironari,
Yoshikawa Shiori,
Yamazoe Taiji,
Mori Taizo,
Osawa Yosuke,
Itoh Shinji,
Fukai Moto,
Yoshizumi Tomoharu,
Taketomi Akinobu,
Mori Masaki,
Kanto Tatsuya
Publication year - 2021
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13667
Subject(s) - myostatin , cirrhosis , medicine , hepatocellular carcinoma , sarcopenia , gastroenterology , fibrosis , body mass index , liver cancer , hepatitis b , liver disease , carcinoma , skeletal muscle
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 patients with non‐alcoholic fatty liver disease–hepatocellular carcinoma (NAFLD‐HCC) 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 skeletal muscle mass index was 44.4 cm 2 /m 2 , and the median body mass index was 23.4 kg/m 2 . Eighty‐two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm 2 /m 2 ). The etiologies of liver disease were hepatitis B virus ( n = 61), hepatitis C virus ( n = 86), and non‐B non‐C hepatitis ( 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 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 patients with NAFLD‐HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production.