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Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B

  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Yao-Chun Hsu
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan

    Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan

    Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan

    Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Terry Cheuk-Fung Yip
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong

    Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong

    State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong
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  • Hsiu J. Ho
    Affiliations
    Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan
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  • Vincent Wai-Sun Wong
    Affiliations
    Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong

    Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong

    State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong
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  • Yen-Tsung Huang
    Affiliations
    Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
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  • Hashem B. El-Serag
    Affiliations
    Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA
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  • Teng-Yu Lee
    Affiliations
    Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

    Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
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  • Ming-Shiang Wu
    Affiliations
    Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Jaw-Town Lin
    Affiliations
    Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan

    Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
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  • Author Footnotes
    ‡ These authors contributed equally as the corresponding senior authors.
    Grace Lai-Hung Wong
    Correspondence
    Corresponding authors. Addresses: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong (G.L.-H. Wong) or Division of Gastroenterology, Taichung Veterans General Hospital, Number 1650, Section 4, Taiwan Avenue, Taichung 40705, Taiwan, (C.-Y. Wu).
    Footnotes
    ‡ These authors contributed equally as the corresponding senior authors.
    Affiliations
    Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong

    Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong

    State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally as the corresponding senior authors.
    Chun-Ying Wu
    Correspondence
    Corresponding authors. Addresses: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong (G.L.-H. Wong) or Division of Gastroenterology, Taichung Veterans General Hospital, Number 1650, Section 4, Taiwan Avenue, Taichung 40705, Taiwan, (C.-Y. Wu).
    Footnotes
    ‡ These authors contributed equally as the corresponding senior authors.
    Affiliations
    Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

    Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

    Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Department of Public Health, China Medical University, Taichung, Taiwan

    National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
    ‡ These authors contributed equally as the corresponding senior authors.
Published:March 15, 2018DOI:https://doi.org/10.1016/j.jhep.2018.02.032

      Highlights

      • A risk score that predicts HCC during antiviral therapy in patients with chronic hepatitis B is developed and validated.
      • The CAMD (cirrhosis, age, male sex, and diabetes mellitus) score requires only simple easily available information.
      • Patients with a CAMD score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.

      Background & Aims

      The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment.

      Methods

      This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26–3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong.

      Results

      The c indices for HCC in the development cohort were 0.83 (95% CI 0.81–0.84), 0.82 (95% CI 0.81–0.84), and 0.82 (95% CI 0.80–0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71–0.77), 0.75 (95% CI 0.73–0.78), and 0.75 (95% CI 0.72–0.77) during the first three years, and 0.76 (95% CI 0.74–0.78) and 0.76 (95% CI 0.74–0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks.

      Conclusions

      The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy.

      Lay summary

      This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75–80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.

      Graphical abstract

      Keywords

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