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

• Published in: Clinical and molecular hepatology Vol. 28; no. 2; pp. 219 - 231
• Main Authors: Han, Ji Won, Kim, Da In, Nam, Hee Chul, Chang, U Im, Yang, Jin Mo, Song, Do Seon
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association for the Study of the Liver 01.04.2022; Korean Association for the Study of the Liver; 대한간학회
• Subjects: Animals; Humans; Liver - pathology; liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - diagnosis; Myostatin; Original; Rats; Rats, Sprague-Dawley; rifaximin; Rifaximin - pharmacology; sarcopenia; Sarcopenia - complications; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - pharmacology; 내과학; Sarcopenia; Tumor necrosis factor-alpha; Rifaximin; Liver cirrhosis
• ISSN: 2287-2728; 2287-285X
• DOI: 10.3350/cmh.2021.0082

Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear. 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-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease. LC and sarcopenia were successfully induced by TAA. Serum TNF-α 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-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α 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-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues. These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.