Assessment and Definition of Myosteatosis
Myosteatosis represents a decline in muscle quality, distinct from sarcopenia (reduced muscle quantity). Its evaluation has moved beyond the limited scope of Body Mass Index (BMI). Computed Tomography (CT) is the most widely used and validated tool in clinical research, primarily utilizing two metrics at the third lumbar vertebra (L3): muscle radiation attenuation (RA, measured in Hounsfield Units, HU) and the intramuscular adipose tissue content (IMAC) ratio. Lower RA or higher IMAC values indicate greater fat infiltration. However, diagnostic cut-offs vary significantly between studies (e.g., using BMI-adjusted RA values or sex-specific IMAC thresholds), leading to wide prevalence estimates and complicating cross-study comparisons. Magnetic Resonance Imaging (MRI) provides superior accuracy for quantifying intramuscular fat fraction but is less accessible. Ultrasound shows potential as a point-of-care tool but lacks standardized criteria. The choice of modality balances accuracy, practicality, and patient-specific factors.
Clinical Impact Across Liver Diseases
Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): Myosteatosis is prevalent in MAFLD and is independently associated with more severe disease phenotypes, including non-alcoholic steatohepatitis (NASH) and significant liver fibrosis. It may serve as a biomarker for disease progression and is linked to an increased risk of hepatocellular carcinoma (HCC) and all-cause mortality.
Liver Cirrhosis: Myosteatosis is common in cirrhosis and is a powerful, independent prognostic marker. It is associated with higher Child-Pugh scores, hepatic encephalopathy, portal hypertension, other decompensating events, and significantly increased long-term mortality. Prognostic models like MELD are improved by incorporating myosteatosis.
Hepatocellular Carcinoma (HCC): In patients with HCC, myosteatosis is associated with worse outcomes, including reduced response to transarterial chemoembolization, shorter progression-free survival in those receiving immunotherapy, and higher rates of postoperative complications and mortality after hepatectomy.
Liver Transplantation (LT): Myosteatosis in LT candidates and recipients is linked to poorer post-transplant outcomes, including increased infections, longer hospital stays, higher costs, and reduced graft and patient survival. It enhances the predictive value of pre-transplant risk scores.
Chronic Viral Hepatitis & Primary Sclerosing Cholangitis (PSC): Emerging evidence suggests a role for myosteatosis in chronic hepatitis C and B, though data are less extensive. In PSC, myosteatosis is an independent predictor of reduced transplant-free survival.
Proposed Pathophysiological Mechanisms
The development of myosteatosis in liver disease is multifactorial, driven by a dysfunctional liver-muscle axis :
Insulin Resistance: Impairs glucose disposal in muscle, increasing free fatty acid uptake and intramuscular lipogenesis.
Hyperammonemia: A hallmark of cirrhosis, ammonia is taken up by muscle, inducing mitochondrial dysfunction and reducing fatty acid oxidation, leading to lipid accumulation.
Chronic Inflammation: Pro-inflammatory cytokines (e.g., IL-6, TNF-α) released from the diseased liver disrupt muscle lipid metabolism and promote fat storage.
Mitochondrial Dysfunction: A central defect leading to impaired oxidative phosphorylation and reduced lipid oxidation in muscle cells.
Other Factors: Elevated plasma Cathepsin D levels correlate with myosteatosis. Nutritional imbalances (both overload and deficiency), genetic factors, and aging-related changes in gene expression (e.g., involving adipogenic regulators) also contribute.
Potential Prevention and Treatment Strategies
Currently, no consensus guidelines exist for treating myosteatosis in liver disease due to a lack of high-level evidence. Proposed strategies are multimodal:
Nutritional Intervention: Tailored to disease stage, focusing on adequate high-quality protein intake (1.2-1.5 g/kg ideal body weight/day), balanced meals low in saturated fat, and specific amino acid supplementation (e.g., leucine, essential amino acids). Energy restriction must be managed to avoid concurrent muscle mass loss.
Exercise Prescription: A combined regimen of progressive aerobic and resistance exercise is foundational. Exercise helps preserve muscle function, enhance lipid oxidation, and may reverse fat infiltration, especially when combined with dietary management.
Pharmacological Therapy: Experimental approaches include agents targeting pathogenic pathways, such as L-ornithine L-aspartate (to lower ammonia) and adiponectin receptor agonists (e.g., AdipoRon), which have shown promise in preclinical models.
Conclusion
Myosteatosis is a critical, yet often overlooked, component of body composition abnormalities in chronic liver disease. It independently predicts morbidity, mortality, and poor treatment outcomes across etiologies, from MAFLD to end-stage cirrhosis and HCC. The lack of standardized assessment hinders clinical translation. Its pathogenesis is complex, involving insulin resistance, hyperammonemia, inflammation, and mitochondrial dysfunction within the liver-muscle axis. Future research must prioritize establishing unified diagnostic criteria and conducting randomized controlled trials to evaluate the efficacy of integrated physical, nutritional, and pharmacological interventions aimed at mitigating myosteatosis and improving patient outcomes.
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The study was recently published in the Journal of Clinical and Translational Hepatology.
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