Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): Development and validation of a predictive score

Hwai I. Yang, Man Fung Yuen, Henry Lik Yuen Chan, Kwang Hyub Han, Pei Jer Chen, Do Young Kim, Sang Hoon Ahn, Chien Jen Chen, Vincent Wai Sun Wong, Wai Kay Seto

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472 Citations (Scopus)


Background: Therapy for chronic hepatitis B reduces the risk of progressing to hepatocellular carcinoma (HCC); however, there is no suitable and accurate means to assess risk. This study aimed to develop and validate a simple scoring system to predict HCC risk in patients with chronic hepatitis B. Methods: The development cohort consisted of 3584 patients without cirrhosis from the community-based Taiwanese REVEAL-HBV study (of whom 131 developed HCC during follow-up), and a validation cohort of 1505 patients from three hospitals in Hong Kong and South Korea (of whom 111 developed HCC during follow-up). We used Cox multivariate proportional hazards model to predict risk of HCC at 3, 5, and 10 years. Variables included in the risk score were sex, age, serum alanine aminotransferase concentration, HBeAg status, and serum HBV DNA level. We calculated the area under receiver operating curve (AUROC) and calibration of predicted and observed HCC risk. Findings: A 17-point risk score was developed, with HCC risk ranging from 0·0% to 23·6% at 3 years, 0·0% to 47·4% at 5 years, and 0·0% to 81·6% at 10 years for patients with the lowest and highest HCC risk, respectively. AUROCs to predict risk were 0·811 (95% CI 0·790-0·831) at 3 years, 0·796 (0·775-0·816) at 5 years, and 0·769 (0·747-0·790) at 10 years in the validation cohort, and 0·902 (0·884-0·918), 0·783 (0·759-0·806), and 0·806 (0·783-0·828), respectively, after exclusion of 277 patients in the validation cohort with cirrhosis. Predicted risk was well calibrated with Kaplan-Meier observed HCC risk. Interpretation: A simple-to-use risk score that uses baseline clinical variables was developed and validated. The score accurately estimates the risk of developing HCC at 3, 5, and 10 years in patients with chronic hepatitis B. Clinicians can use this score to assess risk of HCC in patients with chronic hepatitis B and subsequently make evidence-based decisions about their clinical management. Funding: The Academia Sinica; the National Health Research Institute, Taiwan; and Bristol-Myers Squibb.

Original languageEnglish
Pages (from-to)568-574
Number of pages7
JournalThe Lancet Oncology
Issue number6
Publication statusPublished - 2011 Jun

Bibliographical note

Funding Information:
The REACH-B Working Group meeting was supported through an educational grant from Bristol-Myers Squibb (Singapore). Writing support was provided by Jesse Quigley Jones (MediTech Media Asia Pacific) and funded by Bristol-Myers Squibb. The REVEAL-HBV study was supported by research grants from the Department of Health, Executive Yuan, Taipei, Taiwan; Academia Sinica, Taipei, Taiwan; National Health Research Institute, Chunan, Taiwan; and Bristol-Myers Squibb (Wallingford, CT, USA) to undertake laboratory tests.

Funding Information:
H-IY and C-JC have received speakers’ honoraria and travel expenses from Bristol-Myers Squibb in relation to the REACH-B working group meeting. C-JC has received research grant support from the Department of Health; Academia Sinica and National Health Research Institute, Taiwan; and Bristol-Myers Squibb. M-FY's institution has received a grant from Research Grants Council and Research Fund for Clinical Infectious Diseases, Hong Kong. M-FY has received payment for lectures from GlaxoSmithKline and Bristol-Myers Squibb for work unrelated to this study. HL-YC has received paid consultancy from Bristol-Myers Squibb, Norvatis, Roche, and Merck. P-JC's institution has received a grant for the HCC BRIDGE study. P-JC has received speakers’ honoraria, travel expenses, and payment for development of educational presentation from Bristol-Myers Squibb. VW-SW is a paid advisory board member of Norvatis, Roche, and Gilead; and has received lecture fees from Norvatis, Abbott, and Echosens. K-HH, D-YK, S-HA, and W-KS declare that they have no conflicts of interest.

All Science Journal Classification (ASJC) codes

  • Oncology


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