Applying Cachexia Criteria to Cirrhosis: Considerations for Appropriate Interpretation and Future Research

We read the study by Miwa et al. with great interest [1]. While we commend the authors' efforts to identify prognostic factors, we wish to highlight several points for consideration. First, the Asian Working Group for Cachexia (AWGC) consensus statement explicitly addresses cancer, and several chronic diseases—conditions where hepatic metabolic function is largely preserved [2]. Because the liver plays a central role in energy distribution, various considerations are necessary for diagnosis. In the absence of liver dysfunction, reduced nutritional intake leads to systemic energy deficiency, mobilizing fat before muscle loss occurs. However, in cirrhosis, impaired synthesis of hepatic very low-density lipoprotein (VLDL) can fundamentally alter this sequence. Our study provides a relevant background. Among 859 patients with advanced chronic liver disease, hepatic fat reduction specifically correlated with impaired hepatic reserve (albumin-bilirubin score: Metabolic dysfunction-associated steatotic liver disease[MASLD] r = −0.613, non-MASLD r = −0.233) and sarcopenia, but not with reduced fat tissue mass [3]. This pattern differs from typical cachexia, where fat loss generally precedes or accompanies muscle loss. Furthermore, our body composition study (n = 485) demonstrated that hepatic fat content positively correlates with subcutaneous fat, visceral fat, and muscle mass [4]. These findings suggest that cirrhosis may differ from peripheral cachexia syndrome. Second, diagnostic criteria centered on BMI < 21 kg/m2 may not capture the full spectrum of modern cirrhosis patients. MASLD is becoming increasingly common worldwide, and particularly among Japanese patients with cirrhosis, MASLD prevalence has doubled compared with 5 years ago [5]. The cohort in the present study (8% MASLD) may therefore represent an epidemiologically earlier era. Importantly, patients with BMI ≥ 21 who have severe sarcopenia and impaired liver function could be labeled as “non-cachectic” under current criteria, potentially masking high-risk metabolic phenotypes. Third, terminology strongly shapes clinical interpretation. The term cachexia carries pathophysiological implications derived mainly from oncology—systemic hypercatabolism, cytokine-driven anorexia, and generalized wasting. In cirrhosis, however, the dysfunctional liver itself becomes the metabolic bottleneck, indicating fundamentally different mechanisms. Fourth, this distinction directly influences treatment. In cancer cachexia with preserved hepatic function, early nutritional support is central. In cirrhosis, by contrast, the parallel decline in liver function and metabolic capacity limits the effectiveness of standard nutritional interventions—this is the core clinical dilemma. Management must consider hepatic processing impairment: branched-chain amino acids to bypass first-pass metabolism, late-evening snacks to prevent prolonged fasting catabolism, and interventions aimed at maintaining or restoring residual hepatic synthetic capacity. These points raise the question of whether cachexia frameworks developed for other diseases fully capture cirrhosis-specific metabolic dysfunction. In conclusion, while this study provides valuable prognostic insights, applying diagnostic frameworks developed for other conditions requires careful consideration of the metabolic background unique to cirrhosis—specifically, the fundamentally compromised ability of the liver to allocate energy. As therapeutics that influence body composition advance rapidly, the field is entering a period of major transition. Comprehensive assessment of hepatic metabolic capacity together with body composition will be essential for developing liver-specific strategies to manage metabolic dysfunction in this expanding patient population. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest.