BackgroundThis study aimed to comprehensively assess the diagnostic value of fibrinogen to prealbumin ratio (FPR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) as single markers or in combination in patients with alpha-fetoprotein-negative (AFP-negative) hepatocellular carcinoma (HCC).MethodsA total of 199 healthy controls and 515 AFP-negative patients were enrolled in this study, including 180 HCC inpatients, 151 liver cirrhosis (LC) patients, and 184 chronic hepatitis (CH) cases. Mann–Whitney U or Kruskal–Wallis H test were used to analyze differences between groups in laboratory parameters and clinicopathological features. The diagnostic value of FPR and GPR, alone or in combination, in AFP-negative HCC (AFP-NHCC) patients was determined via a receiver operating characteristic (ROC) curve.ResultsThe levels of FPR and GPR were gradually increased in the development of AFP-NHCC and positively correlated with the tumor size and Barcelona Clinic Liver Cancer (BCLC) stages. Moreover, GPR was associated with Edmondson–Steiner grades. After univariate logistic regression analysis, FPR and GPR remained independent predictors of adverse outcomes. The combination of FPR and GPR had a good ability to detect AFP-NHCC from the control group (area under curve [AUC] = 0.977), AFP-negative CH (AUC = 0.745), and AFP-negative LC (AUC = 0.666). FPR combined with GPR possessed a larger area (0.943, 0.971) and sensitivity (87.50%, 89.81%) than FPR or GPR alone for differentiating AFP-NHCC with tumor size < 3 cm or at the BCLC-A stage.ConclusionsThe pretreatment levels of FPR and GPR played vital roles in the development of AFP-NHCC, especially in patients with early or small AFP-NHCC.