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

Clinical and Molecular Hepatology 2022³â 28±Ç 2È£ p.219 ~ 231
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ÇÑÁö¿ø ( Han Ji-Won ) 
Catholic University College of Medicine Seoul St. Mary¡¯s Hospital Department of Internal Medicine

±è´ÙÀΠ( Kim Da-In ) 
Catholic University College of Medicine St. Vincent¡¯s Hospital Department of Internal Medicine
³²Èñö ( Nam Hee-Chul ) 
Catholic University College of Medicine Seoul St. Mary¡¯s Hospital Department of Internal Medicine
Àå¿ìÀÓ ( Chang U-Im ) 
Catholic University College of Medicine St. Vincent¡¯s Hospital Department of Internal Medicine
¾çÁø¸ð ( Yang Jin-Mo ) 
Catholic University College of Medicine St. Vincent¡¯s Hospital Department of Internal Medicine
¼Ûµµ¼± ( Song Do-Seon ) 
Catholic University College of Medicine St. Vincent¡¯s Hospital Department of Internal Medicine

Abstract


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-¥á 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-¥á 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-¥á levels and sarcopenia. In patients with LS ¡Ã7 kPa or sarcopenia, serum TNF-¥á 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-¥á levels in patients with LS ¡Ã7 kPa. TNF-¥á 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-¥á is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-¥á levels and improving sarcopenia in LC, but these results need to be validated in future studies.

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Sarcopenia; Liver cirrhosis; Tumor necrosis factor-alpha; Rifaximin

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