Serum fibroblast growth factor 21 is a novel biomarker of cachexia in chronic liver disease

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.

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).

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.

Serum FGF21 independently predicts cachexia in CLD and may facilitate earlier identification of at-risk patients, enabling timely intervention to improve clinical outcomes.