Abstract

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.

Highlights

  • This 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)

  • After adjusting for these six predictors, the results of the analysis demonstrated that FPR (β = 0.841, p < 0.001), GPR (β = 15.927, p < 0.001), and Aspartate amino transferase (AST) (β = 0.078, p = 0.023) were still important indicators closely related to the occurrence of AFP-NHCC

  • WBC white blood cells, Hb hemoglobin, TBIL total bilirubin, Alanine aminotransferase (ALT) alanine aminotransferase, AST aspartate amino transferase, PLT platelets, Fib fibrinogen, PA pre-albumin, GGTgamma-glutamyl transpeptidase, FPR fibrinogen to prealbumin ratio, GPR gamma-glutamyl transpeptidase to platelet ratio, AFP-NHCC alpha-fetoprotein-negative hepatocellular carcinoma, AFP alpha-fetoprotein, CH chronic hepatitis, LC liver cirrhosis a AFP-NHCC group vs healthy controls (Mann–Whitney nonparametric U test) b AFP-NHCC group vs AFP-negative CH group (Mann–Whitney nonparametric U test) c AFP-NHCC group vs AFP-negative LC group (Mann–Whitney nonparametric U test)

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Summary

Introduction

This 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). Serum AFP remains the most important and commonly serological diagnostic biomarker, but about 30–40% of overall HCC patients have normal AFP levels (< 20 ng/ mL) [4]. This is referred to as AFP-negative hepatocellular carcinoma (AFP-NHCC) [5]. Even though the proportion of AFP-negative was as high as 15–30% in advanced patients, the American Association for the Study of Liver Diseases updated their practice guidelines in 2011, saying that AFP was no longer recommended for the detection of early HCC [6]. Novel biomarkers with more economical, accurate, and useful predictions for the early diagnosis of HCC are urgently needed, especially for AFP-negative patients

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