Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. 2017

Hiroki Nishikawa, and Hirayuki Enomoto, and Akio Ishii, and Yoshinori Iwata, and Yuho Miyamoto, and Noriko Ishii, and Yukihisa Yuri, and Kunihiro Hasegawa, and Chikage Nakano, and Takashi Nishimura, and Kazunori Yoh, and Nobuhiro Aizawa, and Yoshiyuki Sakai, and Naoto Ikeda, and Tomoyuki Takashima, and Ryo Takata, and Hiroko Iijima, and Shuhei Nishiguchi
Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

BACKGROUND We aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC). METHODS A total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm2 /m2 ). The study cohort was divided into two groups based on the median myostatin value in each gender. RESULTS Our study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4-12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4-8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child-Pugh A patients (n = 123) was 2726.0 pg/mL (578.4-12667.2 pg/mL), whereas that for Child-Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3-12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1-, 3-, 5-, and 7-year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high-myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low-myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1-, 3-, 5-, and 7-year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high-myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low-myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (P < 0.0001) were identified as significant predictors of poorer OS in our multivariate analysis, while higher serum myostatin (P = 0.0855) tended to be a significant adverse predictor. In both genders, PMI, serum albumin, prothrombin time, and branched-chain amino acid to tyrosine ratio showed a significantly inverse correlation with myostatin levels, and serum ammonia levels showed a significantly positive correlation with myostatin levels. CONCLUSIONS Higher serum myostatin levels correlated with muscle mass loss, hyperammonemia, and impaired protein synthesis, as reflected by lower serum albumin levels and lower branched-chain amino acid to tyrosine ratio levels. High serum myostatin levels were also associated with a reduced OS rate in LC patients.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D002423 Cause of Death Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. Causes of Death,Death Cause,Death Causes
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old

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