PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B

Ho Soo Chun, George V. Papatheodoridis, Minjong Lee*, Hye Ah Lee, Yeong Hwa Kim, Seo Hyun Kim, Yun Seo Oh, Su Jin Park, Jihye Kim, Han Ah Lee, Hwi Young Kim, Tae Hun Kim, Eileen L. Yoon, Dae Won Jun, Sang Hoon Ahn, Vana Sypsa, Cihan Yurdaydin, Pietro Lampertico, Jose Luis Calleja, Harry LA JanssenGeorge N. Dalekos, John Goulis, Thomas Berg, Maria Buti, Seung Up Kim, Yoon Jun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background & Aims: 

Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. 


This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012–2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. 


Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00–7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). 


The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. Impact and implications: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5–8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5–8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Original languageEnglish
Pages (from-to)20-30
Number of pages11
JournalJournal of Hepatology
Issue number1
Early online date19 Sept 2023
Publication statusPublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 European Association for the Study of the Liver


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