High serum fibroblast growth factor 21 is associated with inferior hepatocellular carcinoma survival: A prospective cohort study

Background & Aims Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 levels and HCC survival in a large prospective cohort. Methods 825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P-trend = .014) and 1.48 (95% CI: 1.12, 1.97; P-trend = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index >= 25.0 kg/m(2), except for that stronger associations were observed in patients co-occurred more than three metabolic disorder diseases (P-interaction = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P-trend = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P-trend = .195) for LCSS. Conclusions Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism-related prognostic biomarker for HCC.