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

Authors
 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 Janssen  ;  George N Dalekos  ;  John Goulis  ;  Thomas Berg  ;  Maria Buti  ;  Seung Up Kim  ;  Yoon Jun Kim 
Citation
 JOURNAL OF HEPATOLOGY, Vol.80(1) : 20-30, 2024-01 
Journal Title
JOURNAL OF HEPATOLOGY
ISSN
 0168-8278 
Issue Date
2024-01
MeSH
Antiviral Agents / therapeutic use ; Carcinoma, Hepatocellular* / chemically induced ; Carcinoma, Hepatocellular* / etiology ; Child, Preschool ; Cohort Studies ; DNA, Viral ; Hepatitis B e Antigens ; Hepatitis B virus / genetics ; Hepatitis B, Chronic* / complications ; Hepatitis B, Chronic* / drug therapy ; Humans ; Liver Neoplasms* / chemically induced ; Liver Neoplasms* / etiology ; Persistent Infection ; Risk Factors
Keywords
HBeAg-positive chronic hepatitis B ; HBeAg-positive chronic infection ; hepatocellular carcinoma ; risk prediction model
Abstract
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.

Methods: 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.

Results: 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).

Conclusions: 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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0168827823050961
DOI
10.1016/j.jhep.2023.09.011
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198548
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