A multi-centre study of trends in hepatitis B virus-related hepatocellular carcinoma risk over time during long-term entecavir therapy

Seung Up Kim, Yong Eun Chon, Yeon Seok Seo, Hye Won Lee, Han Ah Lee, Mi Na Kim, In Kyung Min, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Won Young Tak, Beom Kyung Kim, Soo Young Park

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3 Citations (Scopus)


The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P >.05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P <.001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development (P =.457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR = 2.069), liver cirrhosis (aHR = 3.771) and Child-Pugh class B (vs A, aHR = 1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR = 0.993; all P <.05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.

Original languageEnglish
Pages (from-to)1352-1358
Number of pages7
JournalJournal of Viral Hepatitis
Issue number12
Publication statusPublished - 2020 Dec 1

Bibliographical note

Funding Information:
This study was in part supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2019R1A2C4070136), and supported by a fund (2019ER510201) granted by the Research of Korea Centers for Disease Control and Prevention. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2020 John Wiley & Sons Ltd

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Virology
  • Infectious Diseases


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