An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B

J Hepatol. 2022 Feb;76(2):311-318. doi: 10.1016/j.jhep.2021.09.025. Epub 2021 Oct 2.


Background & aims: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk.

Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development.

Results: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up.

Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir.

Lay summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.

Keywords: HBV; HCC; antiviral treatment; chronic hepatitis B; deep neural networking; liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Artificial Intelligence / standards*
  • Artificial Intelligence / statistics & numerical data
  • Asian People / ethnology
  • Asian People / statistics & numerical data
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / physiopathology*
  • Cohort Studies
  • Computer Simulation / standards
  • Computer Simulation / statistics & numerical data
  • Female
  • Follow-Up Studies
  • Guanine / analogs & derivatives
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / physiopathology
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Republic of Korea / ethnology
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use
  • White People / ethnology
  • White People / statistics & numerical data


  • Antiviral Agents
  • entecavir
  • Guanine
  • Tenofovir