TY - JOUR
T1 - Myostatin as a fibroblast-activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma
AU - Yoshio, Sachiyo
AU - Shimagaki, Tomonari
AU - Hashida, Ryuki
AU - Kawaguchi, Takumi
AU - Tsutsui, Yuriko
AU - Sakamoto, Yuzuru
AU - Yoshida, Yuichi
AU - Kawai, Hironari
AU - Yoshikawa, Shiori
AU - Yamazoe, Taiji
AU - Mori, Taizo
AU - Osawa, Yosuke
AU - Itoh, Shinji
AU - Fukai, Moto
AU - Yoshizumi, Tomoharu
AU - Taketomi, Akinobu
AU - Mori, Masaki
AU - Kanto, Tatsuya
N1 - Funding Information:
We thank all the participating patients. We are grateful to Ms. Hiromi Tanikawa, Chizu Tokoro and Hiromi Tamada for their technical assistance. We thank H. Nikki March, PhD, from Edanz Group ( https://en‐author‐services.edanzgroup.com/ ) for editing a draft of this manuscript. This research was supported by grants from the Program for Basic and Clinical Research on Hepatitis (AMED; JP18fk0210045).
Publisher Copyright:
© 2021 The Japan Society of Hepatology
PY - 2021/7
Y1 - 2021/7
N2 - 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 cm2/m2, and the median body mass index was 23.4 kg/m2. Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2/m2). 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.
AB - 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 cm2/m2, and the median body mass index was 23.4 kg/m2. Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2/m2). 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.
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U2 - 10.1111/hepr.13667
DO - 10.1111/hepr.13667
M3 - Article
AN - SCOPUS:85106227138
SN - 1386-6346
VL - 51
SP - 803
EP - 812
JO - Hepatology Research
JF - Hepatology Research
IS - 7
ER -
