Combination of inflammatory score/liver function and AFP improves the diagnostic accuracy of HBV-related hepatocellular carcinoma

Cancer Med. 2020 May;9(9):3057-3069. doi: 10.1002/cam4.2968. Epub 2020 Mar 9.

Abstract

Background: Alpha-fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV-related HCC (HBV-HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV-HCC, using the combination of AFP, inflammatory score, and liver function.

Methods: Chronic hepatitis B (CHB) (n = 510) and HBV-HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV-HCC was analyzed, using ROC curve.

Results: It was observed that elderliness, male sex, cirrhosis, HBeAg+ or no-antiviral therapy, and elevation of ALT, AST, neutrophil-lymphocyte ratio (NLR), and AFP were associated with developing HBV-HCC. However, the cut-off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg- HBV-HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815-0.862), 0.533 (95% CI: 0.501-0.565), 0.696 (95% CI: 0.666-0.725), or 0.684 (95% CI: 0.654-0.713) with optimal cut-off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV-HCC, compared to any of the single biomarkers or any other combinations among these patients (except no-cirrhosis).

Conclusions: Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+ , and no-antiviral treatment were independent risk factors for HBV-HCC. AASLD standard of ALT cut-off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg- patients with abnormal AFP may improve the management of HBV-HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV-HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV-HCC from CHB.

Keywords: alanine aminotransferase; alpha-fetoprotein; aspartate aminotransferase; hepatocellular carcinoma; neutrophil-lymphocyte ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Female
  • Follow-Up Studies
  • Hepatitis B / complications*
  • Hepatitis B / virology
  • Hepatitis B virus / isolation & purification
  • Humans
  • Inflammation Mediators / metabolism
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Neutrophils / pathology*
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • alpha-Fetoproteins / metabolism*

Substances

  • AFP protein, human
  • Biomarkers, Tumor
  • Inflammation Mediators
  • alpha-Fetoproteins