ORIGINAL RESEARCH article
Front. Nutr.
Sec. Clinical Nutrition
This article is part of the Research TopicBridging Molecular Drivers with New Therapies for Chronic Liver Disease ProgressionView all articles
Serum Fibroblast Growth Factor 21 Is a Novel Biomarker of Cachexia in Chronic Liver Disease
Provisionally accepted
Takatsugu Tanaka1
Goki Suda1*
Masatsugu Ohara1
Osamu Maehara2Tomoka Yoda1Qingjie Fu1Zijian Yang1Naohiro Yasuura1Akimitsu Meno1Takashi Sasaki1Risako Kohya1Takashi Kitagataya1Naoki Kawagishi1
Masato Nakai1
Takuya Sho1Shunsuke Ohnishi2Naoya Sakamoto1- 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- 2Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
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Background: Cachexia is associated with poor prognosis in chronic liver disease (CLD), yet robust predictors remain poorly defined. This study examined clinical factors and serum biomarkers associated with cachexia in patients with CLD. Methods: We analyzed 356 of 526 patients with CLD who had complete cachexia assessment and available stored serum samples. In a discovery cohort (n=240; Aug 2014–Jun 2023), serum fibroblast growth factor 21 (FGF21), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. Multivariable logistic regression and receiver operating characteristic analyses were used to identify independent predictors and optimal cutoff values. Findings were subsequently evaluated in an independent validation cohort (n=116; Jul 2023–May 2025). Results: Median age was 68 years (range 19–90), 65.8% of participants were male, and 24.6% had cachexia, which independently predicted worse overall survival (hazard ratio 1.64; 95% CI 1.03–2.62; p=0.038). Patients with cachexia had higher serum FGF21 concentrations than those without cachexia (median, 292 vs 177 pg/mL; p=0.002), whereas IL-6 and TNF-α levels did not differ significantly between groups. FGF21 was the only biomarker independently associated with cachexia (odds ratio, 1.71; 95% CI, 1.10–2.66; p=0.016). Advanced Child–Pugh class and platelet count were identified as additional independent clinical predictors. Conclusions: Serum FGF21 independently predicts cachexia in CLD and may facilitate earlier identification of at-risk patients, enabling timely intervention to improve clinical outcomes.
Keywords: biomarker, Cachexia, chronic liver disease, fibroblast growth factor, Liver Cirrhosis
Received: 23 Oct 2025; Accepted: 05 Feb 2026.
Copyright: © 2026 Tanaka, Suda, Ohara, Maehara, Yoda, Fu, Yang, Yasuura, Meno, Sasaki, Kohya, Kitagataya, Kawagishi, Nakai, Sho, Ohnishi and Sakamoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Goki Suda
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