• Gi-Ae Kim, Young-Suk Lim, Seungbong Han, Gwang Hyeon Choi, Won-Mook Choi, Jonggi Choi, Dong Hyun Sinn, Yong-Han Paik, Jeong-Hoon Lee, Yun Bin Lee, Ju-Yeon Cho, Nae-Yun Heo, Man-Fung Yuen, Vincent Wai-Sun Wong, Stephen L Chan, Hwai-I Yang, and Chien-Jen Chen.
• Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea (G.-A.K.).
• Ann. Intern. Med. 2024 Oct 1; 177 (10): 130813181308-1318.

BackgroundA nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB).ObjectiveTo develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation.DesignMultinational cohort study.SettingA community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts).ParticipantsModel development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong.MeasurementsIncidence of HCC.ResultsOver median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold.LimitationValidation in cohorts of other races and receiving antiviral treatment was lacking.ConclusionOur new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment.Primary Funding SourceKorean government.

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