Abstract
Hepatocellular carcinoma is a common type of malignancy with a poor prognosis. Identification and utilisation of markers for monitoring and diagnosis are urgently needed. Alpha-fetoprotein (AFP) and Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) have been proved to be efficient biomarkers for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The combination of the two markers could improve the detection rate. However, these indicators cannot meet the need of clinical diagnosis.It is necessary to discover novel serological markers and more cost-effective, appropriate combination of these markers for the diagnosis and surveillance of HBV-related HCC. Accordingly, in this study, we aimed to evaluate the diagnostic value of γ-glutamyltransferase (γ-GT) to alanine amino transferase (ALT) ratio alone or in combination with AFP and PIVKA-II for HBV-related HCC. 234 patients with HBV-related HCC and 396 patients with chronic hepatitis B (CHB) were enrolled in this study and approved by the institutional review board. Our results showed levels of AFP and PIVKA-II, and γ-GT/ALT ratio in cases with early-stage HCC, HCC, HCC plus HBV DNA positivity, and HCC plus HBV DNA negativity were higher than those in the corresponding CHB control group. Additionally, the levels of serum AFP and PIVKA-II, and the γ-GT/ALT ratio were positively correlated with tumour sizes in patients with HBV-related HCC. The areas under the ROC curves (AUROCs) of the γ-GT/ALT ratio in patients with early-stage HCC, HCC, HCC plus HBV DNA positivity, and HCC plus HBV DNA negativity were 0.795, 0.846,0.855, and 0.837, respectively; AUROCs of combination of the γ-GT/ALT ratio and PIVKA-II were 0.858, 0.928, 0.948, and 0.902, respectively; AUROCs of combination of the γ-GT/ALT ratio and AFP were 0.822, 0.886, 0.896, and 0.873, respectively;AUROCs of combination of the γ-GT/ALT ratio and PIVKA-II with AFP were 0.857, 0.928, 0.946, and 0.907, respectively, and AUROCs of combination of PIVKA-II and AFP were 0.804, 0.904, 0.942, and 0.863, respectively. In conclusion, the γ-GT/ALT ratio was a useful biomarker for the diagnosis of HBV-related HCC and that the combination of AFP and PIVKA-II with the γ-GT/ALT ratio could improve the diagnostic value of these biomarkers for HBV-related HCC. Moreover, the ratio of γ-GT/ALT may be a useful index in monitoring patients for progression of HBV-related HCC.
Highlights
Hepatocellular carcinoma (HCC) and that the combination of AFP and PIVKA-II with the γ-Glutamyl transpeptidase (γ-GT)/ALT ratio could improve the diagnostic value of these biomarkers for hepatitis B virus (HBV)-related HCC
Γ-Glutamyl transpeptidase (γ-GT) is a membrane-binding enzyme that is essential for glutathione synthesis and is considered a biomarker of liver cell damage30. γ-GT in serum is mainly derived from the liver, and the level of γ-GT is abnormally elevated in various hepatobiliary diseases
We examined whether this ratio could be applied to the diagnosis and evaluation of HBV-related HCC and explored whether the combination of the γ-GT/ALT ratio and PIVKA-II and AFP, as known biomarkers for the diagnosis of HCC, could improve the diagnostic value of PIVKA-II and AFP for HBV-related HCC
Summary
HCC and that the combination of AFP and PIVKA-II with the γ-GT/ALT ratio could improve the diagnostic value of these biomarkers for HBV-related HCC. Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) are widely used biomarkers in HCC d iagnosis[13,14,15,16]. These markers have been written into the guidelines for HCC diagnosis published by the National Society of Hepatology of different c ountries[17,18,19]. We examined whether this ratio could be applied to the diagnosis and evaluation of HBV-related HCC and explored whether the combination of the γ-GT/ALT ratio and PIVKA-II and AFP, as known biomarkers for the diagnosis of HCC, could improve the diagnostic value of PIVKA-II and AFP for HBV-related HCC
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