<p>Decreased muscle mass and strength are known as complications of liver fibrosis, which greatly affects the QOL and prognosis of patients. However, the mechanism by which liver fibrosis leads to muscle weakness is unclear. We induced liver fibrosis in mice by bile duct ligation (BDL) and investigated the pathogenic mechanism of muscular atrophy caused by liver fibrosis. In BDL mice, muscle weight, muscle cross-sectional area, and muscle strength decreased early after the procedure, and then further decreased. To search for the causative agent of muscular atrophy we applied BDL mouse serum to cultured myotube cells in vitro and induced muscular atrophy, which was alleviated by TNFRII-Fc fusion protein. Furthermore, administration of TNFRII-Fc preparation (Etanercept) to BDL mice suppressed the decrease in muscle weight and strength in vivo. In BDL mice, TNF-alpha gene expression and blood TNF-alpha concentration were elevated in the liver, but no TNF-alpha elevation was observed in the muscle. In conclusion, the increased TNF-alpha in the injured liver reaches the skeletal muscle through the bloodstream and causes muscle atrophy caused by liver fibrosis, which suggested the importance of the multi-organ linkage behind the complications of liver fibrosis.</p>