Sarcopenia in Chronic Liver Disease: Comparison
Please note this is a comparison between Version 1 by Mimi Kim and Version 2 by Vicky Zhou.

Sarcopenia is prevalent in patients with chronic liver disease, and affected patients tend to have worse clinical outcomes and higher mortality. However, relevant analyses are limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing it.

  • Chronic Liver Disease
  • Sarcopenia

1. Introduction

Sarcopenia is defined as reduced skeletal muscle mass and reduced muscle functionality [1]. Primary sarcopenia is a naturally occurring phenomenon with aging; however, when its severity is due to chronic illness beyond what can be justified by aging alone, it is called secondary sarcopenia [2]. It is also prevalent in patients with chronic liver disease. Sarcopenia is associated with a higher incidence of hepatocellular carcinoma, significant liver fibrosis, hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS), high list mortality, postoperative mortality, and complications in patients with end-stage liver disease [3][4][5][3,4,5]. Sarcopenia is recognized as a disease entity in the International Classification of Disease (ICD-10) [6].

Despite growing research on sarcopenia, progress is hampered by the lack of unified definitions. Several imaging modalities, such as dual energy X-ray absorptiometry (DXA), ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) have made it possible to use body composition assessments for patients with chronic liver disease. Measuring muscle mass with several forms of imaging is less affected by acute illness or cognitive dysfunction compared with measuring strength or physical performance and can be objectively employed in clinical practice [7].

2. Considerations for the Radiologic Evaluation of Sarcopenia

The radiologic evaluation of sarcopenia has the advantage of being able to measure muscle mass objectively and quantitatively. CT and MRI, which are considered to be gold standards for muscle mass measurements, showed high interobserver agreement with Pearson’s correlation coefficient [8][9][39,63]. The measurements of skeletal muscle mass on CT and MRI were also found to be interchangeable. Park et al. showed very good agreement between CT and MRI measurements of skeletal muscle mass at the level of the L3 vertebra (the ICC of reader 1 was 0.928 and that of reader 2 was 0.853) [10][64]. This result is also consistent with studies carried out at the level of the superior mesenteric artery (mostly the first lumbar vertebra) and the level of the third cervical vertebra (C3) [11][9][57,63]. In addition, it is possible to measure skeletal muscle retrospectively because most patients with chronic liver disease frequently undergo radiologic evaluations.

In previous studies, different cut-off values were applied according to sex, etiology of the disease, ethnicity, and the modality used. The SMI values of male patients were significantly higher than those of female patients; however, the frequency of sarcopenia among male patients was higher than that in female patients when sex-specific cut-offs were applied [12][13][8][31,35,39]. Previous studies have examined the association between non-alcoholic fatty liver disease (NAFLD) and hepatitis B or C viral cirrhosis with sarcopenia using DXA as the assessment tool [14][15][16][17][12,13,25,65]. A study from Korea reported the association of NAFLD with sarcopenia using CT [18][45], with a cut-off value defined as 1 standard deviation below the sex-specific mean value for a young healthy population: 8.37 cm2/(kg/m2) for men and 7.47 cm2/(kg/m2) for women. After the publication of the EWGSOP guidelines, some studies were designed to determine specific cut-off values for sarcopenia assessment using CT for Japanese and Asian adults. Two studies provided PMI cut-off values of 3.74 and 6.36 cm2/m2 for men and 2.29 and 3.92 cm2/m2 for women, respectively, based on Japanese liver donor data. The authors suggested that that the cut-off values in Western studies could be different from the actual values in Asian populations due to differences in body sizes, lifestyles, and ethnicities [16][19][25,66]. Further studies to define sarcopenia should be conducted according to ethnicity and the etiology of hepatic disease.

There is a need for standardized CT, as CT parameters such as tube potential, the use of a contrast agent, and slide thickness also affect the assessment of skeletal muscle. A reduction in tube potential from 140 to 80 kV leads to a 5.2% decrease in SMI [20][67], and the use of contrast media overestimates the average SMI by up to 2.8% [21][68]. Differences in slice thickness of 10 and 2 mm can result in a 1.9% smaller SMI [21][68]. Contrast enhancement, moreover, strongly influences the value of skeletal muscle density [22][23][69,70].

Moreover, radiological assessment does not always reflect strength or physical performance [24][25][26][27][71,72,73,74]. However, further research is needed to determine which parameters of muscle strength and physical performance are complemented by radiological assessment. In 2018, EWGSOP recommended that if a patient has low muscle strength, is defined as probable sarcopenia, and has low muscle quantity or quality, they can be diagnosed as sarcopenia [1] because it is recognized that strength is better than muscle mass in predicting adverse outcomes. Sinclair et al. showed that the model for the end-stage liver disease (MELD)-handgrip strength bivariate Cox model is superior to the MELD-CT muscle Cox model (p < 0.001) in predicting mortality [28][18]. For muscle strength, the use of a handheld dynamometer is a valid and reliable method with high interrater and intrarater reliability. Further, the short physical performance battery and gait speed provide good measurement properties for the assessment of physical performance [1][29][1,75].

3. Conclusions

The evaluation of sarcopenia is crucial in patients with chronic liver disease, as well as other chronic illness, because sarcopenia is one of the important prognostic factors [4][5][4,5]. Overall, CT and MRI are considered the gold standard for evaluating sarcopenia and are frequently performed in patients with chronic liver disease for the evaluation of hepatocellular carcinoma or complications of portal hypertension. CT shows excellent performance in estimating the quality and quantity of muscle, and many studies have reported variable measurement methods and cut-off values in patients with chronic liver disease. MRI could be a competent imaging modality for muscle quality evaluation by measuring intramuscular fat content with MRS or DIXON-based MRI, as well as muscle mass by measuring the area, which requires further validations in chronic liver disease. DXA is a reliable alternative for clinical use when a CT scan is not clinically indicated or available. Unification of the measurement method and cut-off value would facilitate more systematic and universal prognosis evaluations in patients with chronic disease.

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