Myosteatosis in Cirrhosis: A Review of Diagnosis, Pathophysiological Mechanisms and Potential Interventions
Maryam Ebadi, Cynthia Tsien, Rahima A. Bhanji, Abha R. Dunichand‐Hoedl, Elora Rider, Maryam Motamedrad, Vera C. Mazurak, Vickie E. Baracos, Aldo J. Montaño‐Loza
Abstract
Myosteatosis, or pathological excess fat accumulation in muscle, has been widely defined as a lower mean skeletal muscle radiodensity on computed tomography (CT). It is reported in more than half of patients with cirrhosis, and preliminary studies have shown a possible association with reduced survival and increased risk of portal hypertension complications. Despite the clinical implications in cirrhosis, a standardized definition for myosteatosis has not yet been established. Currently, little data exist on the mechanisms by which excess lipid accumulates within the muscle in individuals with cirrhosis. Hyperammonemia may play an important role in the pathophysiology of myosteatosis in this setting. Insulin resistance, impaired mitochondrial oxidative phosphorylation, diminished lipid oxidation in muscle and age-related differentiation of muscle stem cells into adipocytes have been also been suggested as potential mechanisms contributing to myosteatosis. The metabolic consequence of ammonia-lowering treatments and omega-3 polyunsaturated fatty acids in reversing myosteatosis in cirrhosis remains uncertain. Factors including the population of interest, design and sample size, single/combined treatment, dosing and duration of treatment are important considerations for future trials aiming to prevent or treat myosteatosis in individuals with cirrhosis.