Reevaluating Myosteatosis Criteria in Cirrhosis: Fluid and Gender Considerations

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosisJournal of HepatologyPreviewSarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. Full-Text PDF Open Access We read with great interest the recent article by Di Cola et al., entitled 'Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis', published in the Journal of Hepatology. The authors acknowledged the prevalence and profoundly detrimental impact of myosteatosis, whether occurring independently or in conjunction with sarcopenia, on the clinical course and outcomes of patients with liver cirrhosis (1Di Cola S. D'Amico G. Caraceni P. et al.Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.J Hepatol. 2024; (Published online May 21)https://doi.org/10.1016/j.jhep.2024.05.020Abstract Full Text Full Text PDF Google Scholar). However, the criteria used to categorize cirrhotic patients as having myosteatosis in their study warrant re-evaluation. This letter seeks to initiate a dialogue with the authors to further explore this issue, illustrating with examples and discussing potential directions for future research. Values derived from cancer populations, such as a mean third lumbar vertebra (L3) muscle radiodensity cutoff of <33 Hounsfield Units (HU) for patients with a BMI ≥25 kg/m2 and <41 HU for those with a BMI <25 kg/m2, are often applied to predict clinical outcomes in patients with cirrhosis (2Martin L. Birdsell L. Macdonald N. et al.Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.J Clin Oncol. 2013; 31: 1539-1547https://doi.org/10.1200/JCO.2012.45.2722Crossref PubMed Scopus (1848) Google Scholar, 3Ebadi M. Tsien C. Bhanji R.A. et al.Myosteatosis in Cirrhosis: A Review of Diagnosis, Pathophysiological Mechanisms and Potential Interventions.Cells. 2022; 11 (Published 2022 Apr 4): 1216https://doi.org/10.3390/cells11071216Crossref PubMed Scopus (25) Google Scholar). Di Cola et al. also utilized these metrics to assess the myosteatosis status of their study participants (1Di Cola S. D'Amico G. Caraceni P. et al.Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.J Hepatol. 2024; (Published online May 21)https://doi.org/10.1016/j.jhep.2024.05.020Abstract Full Text Full Text PDF Google Scholar). However, it should be noted that fluid retention, which is prevalent in many patients with cirrhosis, may compromise the applicability of these cancer-specific, BMI-dependent cutoffs for myosteatosis in cirrhotic populations (3Ebadi M. Tsien C. Bhanji R.A. et al.Myosteatosis in Cirrhosis: A Review of Diagnosis, Pathophysiological Mechanisms and Potential Interventions.Cells. 2022; 11 (Published 2022 Apr 4): 1216https://doi.org/10.3390/cells11071216Crossref PubMed Scopus (25) Google Scholar). Since BMI is primarily an indicator of fat mass, fluid retention (e.g., ascites and lower limb edema) could artificially elevate a cirrhotic patient's weight and, consequently, their BMI. This elevation is due to fluid accumulation, not an increase in fat or muscle mass, potentially leading to inaccurate categorization based on BMI. As a result, a disproportionately high number of cirrhotic patients could be misclassified as having a BMI ≥25 kg/m2. Patients with a BMI close to but below 25 kg/m2 might be especially affected by fluid accumulation, potentially leading to inappropriate myosteatosis classifications and significant clinical consequences. For example, consider a cirrhotic patient with fluid accumulation. This patient, with a height of 1.70 meters and an actual weight of 70 kilograms (BMI 24.22 kg/m2), gains 5 kilograms due to fluid retention, increasing the BMI to 25.95 kg/m2. The patient's L3 muscle radiodensity is 35 HU. According to established cutoffs, radiodensity < 41 HU for BMI < 25 kg/m2 and < 33 HU for BMI ≥ 25 kg/m2 indicates myosteatosis. Due to fluid retention-induced BMI increase, the patient is misclassified into the BMI ≥ 25 kg/m2 category, applying the stricter < 33 HU cutoff. Despite having a radiodensity of 35 HU, the patient is incorrectly classified as not having myosteatosis. While the strong correlation between skeletal muscle areas at L3 and whole-body muscle mass (r2 = 0.855, p < 0.01) confirms that abdominal CT scans at the third lumbar vertebra are reliable for assessing whole-body muscle mass, BMI values are less dependable among cirrhotic patients with fluid accumulation (4Shen W. Punyanitya M. Wang Z. et al.Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.Journal of applied physiology (Bethesda, Md. : 1985). 2004; 97: 2333-2338https://doi.org/10.1152/japplphysiol.00744.2004Crossref PubMed Scopus (1244) Google Scholar, 5Ebadi M. Tsien C. Bhanji R.A. et al.Skeletal Muscle Pathological Fat Infiltration (Myosteatosis) Is Associated with Higher Mortality in Patients with Cirrhosis.Cells. 2022; 11: 1345https://doi.org/10.3390/cells11081345Crossref PubMed Scopus (24) Google Scholar). The example we provide illustrates how fluid retention-induced BMI inflation might lead to inappropriate clinical assessments and misguided treatment decisions/planning. We therefore highly encourage the authors to revisit their data considering the patients' BMI and fluid accumulation status. Although the authors mentioned that they recorded data on the dry weight of patients with ascites and other forms of fluid retention (1Di Cola S. D'Amico G. Caraceni P. et al.Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.J Hepatol. 2024; (Published online May 21)https://doi.org/10.1016/j.jhep.2024.05.020Abstract Full Text Full Text PDF Google Scholar), the methodology used for calculating BMI in their study remains unclear. The example we present underscores the necessity of applying the BMI-based definition of myosteatosis with particular care and consideration of the potential impact of fluid retention in patients with cirrhosis. Even if cases similar to our example are not prevalent in the authors' study sample, the issue remains critical from the perspective of patient-centered care and for the broader population of cirrhotic patients outside their study. This aspect should not be overlooked. Moreover, although the authors classify patients as having sarcopenia using gender-specific metrics (i.e., <50 cm2/m2 for men and <39 cm2/m2 for women, based on the validated skeletal mass index cutoffs), they did not apply similar considerations for classifying myosteatosis. Given that the lipid storage capacity of skeletal muscle is higher in females than in males, it is crucial to consider gender differences when assessing myosteatosis (3Ebadi M. Tsien C. Bhanji R.A. et al.Myosteatosis in Cirrhosis: A Review of Diagnosis, Pathophysiological Mechanisms and Potential Interventions.Cells. 2022; 11 (Published 2022 Apr 4): 1216https://doi.org/10.3390/cells11071216Crossref PubMed Scopus (25) Google Scholar, 6Lundsgaard A.M. Kiens B. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity.Frontiers in endocrinology. 2014; 5: 195https://doi.org/10.3389/fendo.2014.00195Crossref PubMed Scopus (179) Google Scholar, 7Kamiliou A. Lekakis V. Chrysavgis L. et al.Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis.Hepatology international. 2024; 18: 688-699https://doi.org/10.1007/s12072-023-10632-8Crossref Scopus (0) Google Scholar). Importantly, in daily clinical practice, early detection and incorporation of myosteatosis into the management protocols of these patients are vital to prevent liver-related complications and improve survival (7Kamiliou A. Lekakis V. Chrysavgis L. et al.Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis.Hepatology international. 2024; 18: 688-699https://doi.org/10.1007/s12072-023-10632-8Crossref Scopus (0) Google Scholar). However, we need an accurate and validated definition of myosteatosis. A meta-analysis reported that the prevalence of myosteatosis was significantly higher at 56% in studies using BMI-based criteria compared to 36% and 21% in those using gender-specific or other criteria, respectively (p < 0.01) (7Kamiliou A. Lekakis V. Chrysavgis L. et al.Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis.Hepatology international. 2024; 18: 688-699https://doi.org/10.1007/s12072-023-10632-8Crossref Scopus (0) Google Scholar). This indicates the need for a consensus that balances the effects of fluid retention-inflated BMI values and gender differences. Establishing and validating such a consensus is essential to define the optimal criteria for assessing myosteatosis in the context of cirrhosis in future clinical practice. D.S.: Manuscript writing & Study design. G.Z and Z.D.: Manuscript revision & Study design. We declare there is no any conflict of interest. None