Prediction Model with HLA-A*33:03 Reveals Number of Days to Develop Liver Cancer from Blood Test

Int J Mol Sci. 2023 Mar 1;24(5):4761. doi: 10.3390/ijms24054761.


The development of liver cancer in patients with hepatitis B is a major problem, and several models have been reported to predict the development of liver cancer. However, no predictive model involving human genetic factors has been reported to date. For the items incorporated in the prediction model reported so far, we selected items that were significant in predicting liver carcinogenesis in Japanese patients with hepatitis B and constructed a prediction model of liver carcinogenesis by the Cox proportional hazard model with the addition of Human Leukocyte Antigen (HLA) genotypes. The model, which included four items-sex, age at the time of examination, alpha-fetoprotein level (log10AFP) and presence or absence of HLA-A*33:03-revealed an area under the receiver operating characteristic curve (AUROC) of 0.862 for HCC prediction within 1 year and an AUROC of 0.863 within 3 years. A 1000 repeated validation test resulted in a C-index of 0.75 or higher, or sensitivity of 0.70 or higher, indicating that this predictive model can distinguish those at high risk of developing liver cancer within a few years with high accuracy. The prediction model constructed in this study, which can distinguish between chronic hepatitis B patients who develop hepatocellular carcinoma (HCC) early and those who develop HCC late or not, is clinically meaningful.

Keywords: cox proportional-hazards regression model; hepatitis B virus; hepatocellular carcinoma; human leukocyte antigen; prediction.

MeSH terms

  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / virology
  • HLA-A Antigens* / genetics
  • Hematologic Tests
  • Hepatitis B, Chronic* / complications
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / virology
  • ROC Curve


  • HLA-A Antigens