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A multi‐center 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
First published: 27 August 2020
https://doi.org/10.1111/jvh.13384
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/jvh.13384
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Abstract 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/day were stratified into three groups according to entecavir start time: early (2007–2010), middle (2011–2012), and late (2013–2014) cohorts Among 2,442 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>0.05 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<0.001), whereas entecavir start time (early vs. middle vs. late cohorts) did not affect the risk of HCC development (p=0.457). 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<0.05). 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 non‐viral factors are required.
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