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

  • Author Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Hwi Young Kim
    Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Affiliations
    Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
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  • Author Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Pietro Lampertico
    Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Affiliations
    Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy

    CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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  • Author Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Joon Yeul Nam
    Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Affiliations
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Hyung-Chul Lee
    Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    Affiliations
    Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Seung Up Kim
    Affiliations
    Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Dong Hyun Sinn
    Affiliations
    Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Yeon Seok Seo
    Affiliations
    Department of Internal Medicine, Korea University Anam Hospital, Korea University College, Republic of Korea
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  • Han Ah Lee
    Affiliations
    Department of Internal Medicine, Korea University Anam Hospital, Korea University College, Republic of Korea

    Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea
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  • Soo Young Park
    Affiliations
    Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
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  • Young-Suk Lim
    Affiliations
    Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea
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  • Eun Sun Jang
    Affiliations
    Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
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  • Eileen L. Yoon
    Affiliations
    Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea

    Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
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  • Hyoung Su Kim
    Affiliations
    Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
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  • Sung Eun Kim
    Affiliations
    Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Republic of Korea
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  • Sang Bong Ahn
    Affiliations
    Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Republic of Korea
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  • Jae-Jun Shim
    Affiliations
    Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea
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  • Soung Won Jeong
    Affiliations
    Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
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  • Yong Jin Jung
    Affiliations
    Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Republic of Korea
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  • Joo Hyun Sohn
    Affiliations
    Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Republic of Korea
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  • Yong Kyun Cho
    Affiliations
    Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Dae Won Jun
    Affiliations
    Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
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  • George N. Dalekos
    Affiliations
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
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  • Ramazan Idilman
    Affiliations
    Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
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  • Vana Sypsa
    Affiliations
    Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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  • Thomas Berg
    Affiliations
    Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
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  • Maria Buti
    Affiliations
    Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
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  • Jose Luis Calleja
    Affiliations
    Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain
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  • John Goulis
    Affiliations
    4th Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, General Hospital of Thessaloniki “Hippokratio”, Thessaloniki, Greece
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  • Spilios Manolakopoulos
    Affiliations
    2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
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  • Harry L.A. Janssen
    Affiliations
    Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
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  • Myoung-jin Jang
    Affiliations
    Medical Research Collaboration Center, Seoul National University Hospital, Seoul, Republic of Korea
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  • Yun Bin Lee
    Affiliations
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Yoon Jun Kim
    Affiliations
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Jung-Hwan Yoon
    Affiliations
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    ‡ These 2 authors contributed equally to this work as co-corresponding authors.
    George V. Papatheodoridis
    Correspondence
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece; Tel.: +30-2132061115, fax: +30-2107462601.
    Footnotes
    ‡ These 2 authors contributed equally to this work as co-corresponding authors.
    Affiliations
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
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  • Author Footnotes
    ‡ These 2 authors contributed equally to this work as co-corresponding authors.
    Jeong-Hoon Lee
    Correspondence
    Corresponding author. Addresses: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea; Tel.: +82-2-2072-2228, fax: +82-2-743-6701;
    Footnotes
    ‡ These 2 authors contributed equally to this work as co-corresponding authors.
    Affiliations
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    † These 4 authors contributed equally to this work as co-first authors.
    ‡ These 2 authors contributed equally to this work as co-corresponding authors.
Published:October 01, 2021DOI:https://doi.org/10.1016/j.jhep.2021.09.025

      Highlights

      • A new HCC prediction model (PLAN-B) was developed using machine learning algorithms in antiviral-treated patients with chronic hepatitis B.
      • The utility of the model was validated in independent Korean and Caucasian cohorts.
      • PLAN-B comprises 10 baseline parameters: cirrhosis, age, platelet count, ETV/TDF, sex, serum ALT and HBV DNA, albumin and bilirubin levels, and HBeAg status.
      • The PLAN-B model demonstrated satisfactory predictive performance for HCC development and outperformed other risk scores.

      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.

      Graphical abstract

      Keywords

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