Validation of three staging systems for hepatocellular carcinoma (JIS score, biomarker-combined JIS score and BCLC system) in 4,649 cases from a Japanese nationwide survey

Dig Dis. 2014;32(6):717-24. doi: 10.1159/000368008. Epub 2014 Oct 29.


Objective: Clinical staging is very important for optimal therapeutic strategy and prognostic prediction in patients with hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and best-validated method for HCC. Similarly, the conventional Japan Integrated Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also been reported to effectively stratify HCC patients. The aim of this study was to evaluate the performance of these three staging systems for prognostic prediction.

Methods: A total of 4,649 HCC patients were included in this study. A multivariate analysis identified the independent risk factors associated with overall survival. The stratification ability and the suitability as a prognostic model of the three staging systems were compared.

Results: Multivariate analysis revealed that male sex, higher Child-Pugh score, tumor size >2.0 cm, multiple tumors, vascular invasion, higher alpha-fetoprotein (AFP) level, higher des-gamma-carboxyprothrombin level, higher Lens culinaris agglutinin-reactive AFP level, and a performance status of 3-4 were independent risk factors in HCC. The independent homogenizing ability and stratification value of the bm-JIS score were higher than those of the c-JIS score and the BCLC system (χ(2) = 972.7581, 758.1041 and 679.6832, respectively). Moreover, the bm-JIS score had the lowest Akaike Information Criteria value, followed by the c-JIS score and the BCLC system (9,844.278, 10,054.93 and 10,131.35, respectively).

Conclusions: Our results suggest that the bm-JIS score offers good stratification ability and is a better prognostic predictor than the c-JIS score and the BCLC system.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers / metabolism
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cross-Sectional Studies
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Japan
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging / methods*
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors / metabolism
  • Prothrombin / metabolism
  • Spain
  • Survival Analysis
  • alpha-Fetoproteins / metabolism


  • Biomarkers
  • Biomarkers, Tumor
  • Protein Precursors
  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Prothrombin