Comment on “Using Serum Creatinine‐to‐Cystatin C Ratio to Predict Sarcopenia in Patients With Liver Cirrhosis”

We read with great interest the article by Shibamoto et al., titled “Using Serum Creatinine-to-Cystatin C Ratio to Predict Sarcopenia in Patients With Liver Cirrhosis,” recently published in Hepatology Research [1]. The authors present a compelling retrospective cohort study validating the serum creatinine-to-cystatin C ratio (CCR) as a simple biomarker for diagnosing sarcopenia and predicting prognosis in patients with liver cirrhosis (LC). This work addresses a significant clinical need for accessible tools to manage this debilitating complication. This study's methodological strength lies in its adoption of the contemporary consensus definition for sarcopenia, which incorporates both low muscle mass (assessed by skeletal muscle index, SMI) and poor muscle function (evaluated by handgrip strength, HGS) [2]. The key findings are noteworthy: a lower CCR was independently associated with sarcopenia and served as an independent predictor of patient survival, with a prognostic value comparable to that of ascites. This positions CCR as a practical, serum-based tool, particularly valuable for outpatient and elderly populations where access to complex body composition analysis is limited. Although we commend this important contribution, several considerations for future research arise. As the authors appropriately note, CCR can be affected by fluctuations in renal function and inflammatory status. Cystatin C (Cys-C) is recognized as an inflammation-sensitive marker. Its concentration can increase during systemic inflammation, independently of changes in glomerular filtration rate (GFR). In patients with LC, especially during episodes of infection or acute decompensation, it remains to be clarified to what extent a decline in CCR reflects true muscle depletion versus an inflammation-driven rise in Cys-C. In advanced cirrhosis, decreased synthesis of creatine in the liver and skeletal muscles can lead to reduced serum creatinine concentrations, which may overestimate the GFR when using creatinine-based equations. Consequently, CCR is influenced by a confluence of factors: skeletal muscle mass, renal function, and inflammatory status. In clinical practice, CCR values should be interpreted within the broader clinical context, especially in patients with significant fluctuations in renal function or acute inflammatory events, such as infection or decompensation. Future studies incorporating inflammatory markers, such as high-sensitivity C-reactive protein or interleukin-6, could help disentangle the complex interplay between inflammation, CCR, and sarcopenia. Furthermore, as the study cohort was predominantly Japanese, the generalizability of the CCR diagnostic cut-offs and its predictive performance may be limited. This is due to known ethnic variations in creatinine generation, body composition, and the etiological spectrum of LC—for instance, the relatively low prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population. We echo the authors' call for external validation in multi-ethnic, prospective, multicenter cohorts. Additionally, the study primarily establishes cross-sectional and longitudinal associations of CCR as a diagnostic and prognostic marker. An intriguing question for future investigation is whether serial measurements of CCR could sensitively track the progression of sarcopenia or the response to therapeutic interventions, such as nutritional support or physical exercise. Exploring its potential as a dynamic monitoring tool represents a promising research direction. Although future studies are needed to address these points, the current study by Shibamoto and colleagues delivers clinically relevant and pragmatic insights into sarcopenia management in patients with LC. The CCR, derived from routine biochemical parameters, offers advantages of cost-effectiveness and repeatability, holding promise for wider clinical application in risk stratification and decision-making. We look forward to prospective studies that will consolidate these findings and further refine its application in personalized patient management. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.