Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis

Background/Aims: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear. Methods: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-alpha levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease. Results: LC and sarcopenia were successfully induced by TAA. Serum TNF-alpha levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-alpha levels and sarcopenia. In patients with LS >= 7 kPa or sarcopenia, serum TNF-alpha levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-alpha levels in patients with LS >= kPa. TNF-alpha was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues. Conclusions: These results suggest that serum TNF-alpha is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-alpha levels and improving sarcopenia in LC, but these results need to be validated in future studies.