Predictive score for hepatocellular carcinoma after hepatitis B e antigen loss in patients treated with entecavir or tenofovir

Tae Seop Lim, Hyun Woong Lee, Jung Il Lee, In Hee Kim, Chang Hun Lee, Byoung Kuk Jang, Woo Jin Chung, Hyung Joon Yim, Sang Jun Suh, Yeon Seok Seo, Han Ah Lee, Jung Hwan Yu, Jin Woo Lee, Sang Gyune Kim, Young Seok Kim, Soo Young Park, Won Young Tak, Soon Sun Kim, Jae Youn Cheong, Soung Won JeongJae Young Jang, Woo Sun Rou, Byung Seok Lee, Seung Up Kim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The risk of developing hepatocellular carcinoma (HCC) after hepatitis B e antigen seroclearance (ESC) remains unclear. We established and validated a new risk prediction model for HCC development after ESC in patients with chronic hepatitis B (CHB) receiving antiviral therapy (AVT). Between 2006 and 2016, 769 patients (training cohort) and 1,061 patients (validation cohort) with CHB who experienced ESC during AVT using entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were recruited. In the multivariate analysis, male sex (hazard ratio [HR] = 2.092; 95% confidence interval [CI] = 1.152-3.800), cirrhosis (HR = 5.141; 95% CI = 2.367-11.167) and fibrosis-4 index (FIB-4) of '3.25 (HR = 2.070; 95% CI = 1.184-3.620) were the independent risk factors for HCC development (all P '.05). Accordingly, a novel HCC-ESCAVT model was developed (1x[sex: male = 1, female = 0] + 3x(cirrhosis = 1, noncirrhosis = 0) + 1x(FIB-4: '3.25 = 1, ≤3.25 = 0). The cumulative risk for HCC development was significantly different among the risk groups based on the HCC-ESCAVT category (0-1, 2-4 and 5 for the low-, intermediate- and high-risk groups, respectively) (overall P '.001, log-rank test). The area under the receiver operating characteristic curve (AUC) for predicting HCC development 3, 5 and 10 years after ESC was 0.791, 0.771 and 0.790, respectively (all P '.05). The predictive value of the HCC-ESCAVT model was similar in the validation cohort (AUC = 0.802, 0.774 and 0.776 at 3, 5 and 10 years, respectively; all P '.05). Hence, we have developed and validated a new HCC-ESCAVT model for HCC development, which includes male sex, cirrhosis and FIB-4 of '3.25 as constituent variables.

Original languageEnglish
Pages (from-to)1052-1060
Number of pages9
JournalJournal of Viral Hepatitis
Issue number10
Publication statusPublished - 2020 Oct 1
Externally publishedYes

Bibliographical note

Funding Information:
This work was in part supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.

Publisher Copyright:
© 2020 John Wiley & Sons Ltd


  • hepatitis B
  • hepatitis B e antigen
  • hepatocellular carcinoma
  • risk prediction

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology
  • Hepatology


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