The evaluation of sarcopenia in chronic liver disease

Dhaliwal, Amritpal ORCID: 0000-0001-5919-6456 (2023). The evaluation of sarcopenia in chronic liver disease. University of Birmingham. Ph.D.

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Abstract

End stage liver disease (ESLD) has a significant impact on the homeostasis of muscle, with observed reductions in muscle mass, performance and function due to an ongoing catabolic state. This study carried out a multi-modal assessment, including MRI, muscle functional measures and analysis of serum and muscle biopsies, to evaluate and phenotype sarcopenia and frailty in those with ESLD and to determine the mechanisms driving compromised muscle health.

The study recruited 53 patients with ESLD, 39 of whom completed the multi-modal assessments, and 18 age and sex matched healthy controls. The ESLD cohort had a median age of 57.5 (IQR 50.0-61.3) years with 61.9% male predominance and the controls had a median age of 51.5 (IQR 33.0-63.3) years with 61.1% who were male . The disease aetiologies were 47.9% alcohol related disease, 14.3% NAFLD and 33.3% autoimmune disease. The findings highlighted that reduced muscle mass, quality and function (as measured by strength and performance) were reduced in those with ESLD compared to healthy controls, that when evaluating changes in muscle composition, muscle mass, quality and function should all be considered in those with ESLD. This study found that quadriceps measures of muscle mass from MRI and ultrasound, correlated to the commonly used standard of L3 SMI, supporting its future use as a functionally relevant muscle group. Further, the results showed that muscle mass, quality and function were impacted by ascites, hepatic encephalopathy, aetiology of ESLD, age and sex, supporting the consideration of these variables when evaluating muscle health in ESLD. Finally, the muscle phenotype in patients with ESLD was broken down in to those with adequate muscle mass and function, those with adequate mass but inadequate function and those with inadequate mass and function. Comparing these distinct phenotypes revealed clear differences in the mechanisms potentially driving muscle wasting in ESLD at a molecular and transcriptomic level; notably altered adrenal steroids, mitochondrial dysfunction, cellular senescence, altered regulation of protein synthesis and pro-inflammatory pathways were identified as differential influences on muscle phenotype. Taken together, these data support the need for a multi-modal assessment to evaluate sarcopenia and frailty in ESLD with targets for future research highlighted.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):