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Keywords:

  • cirrhosis;
  • IGF-1;
  • myostatin;
  • proteasome;
  • sarcopaenia;
  • skeletal muscle;
  • ubiquitin

Abstract

Background

Chronic diseases, including cirrhosis, are often accompanied by protein-energy malnutrition and muscle loss, which in turn negatively affect quality of life, morbidity and mortality. Unlike other chronic conditions, few data are available on the molecular mechanisms underlying muscle wasting in this clinical setting.

Aims

To assess mechanisms of muscle atrophy in patients with cirrhosis.

Methods

Nutritional [subjective global assessment (SGA) and anthropometry] and metabolic assessment was performed in 30 cirrhotic patients awaiting liver transplantation.

Rectus abdominis biopsies were obtained intraoperatively in 22 cirrhotic patients and in 10 well-nourished subjects undergoing elective surgery for non-neoplastic disease, as a control group. Total RNA was extracted and mRNA for atrogenes (MuRF-1, Atrogin-1/MAFbx), myostatin (MSTN), GSK3β and IGF-1 was assayed.

Results

A total of 50% of cirrhotic patients were malnourished based on SGA, while 53% were muscle-depleted according to mid-arm muscle area (MAMA<5th percentile). MuRF-1 RNA expression was significantly increased in malnourished cirrhotic patients (SGA-B/C) vs. well-nourished patients (SGA-A) (P = 0.01). The phosphorylation of GSK3β was up-regulated in cirrhotic patients with hepatocellular carcinoma (HCC) vs. patients without tumour (P < 0.05).

Conclusions

Muscle loss is frequently found in end-stage liver disease patients. Molecular factors pertaining to signalling pathways known to be involved in the regulation of muscle mass are altered during cirrhosis and HCC.