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Original research
No difference in hepatocellular carcinoma risk between chronic hepatitis B patients treated with entecavir versus tenofovir
  1. Feng Su1,
  2. Kristin Berry2,
  3. George N Ioannou1,2,3
  1. 1 Division of Gastroenterology, University of Washington, Seattle, Washington, USA
  2. 2 Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, USA
  3. 3 Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, USA
  1. Correspondence to Dr Feng Su, University of Washington, Seattle, WA 98195-0005, USA; fsu{at}


Objective Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line agents for the treatment of chronic hepatitis B (CHB). Recent studies have challenged the assumption that these agents are equally effective at preventing hepatocellular carcinoma (HCC). We aimed to determine whether the risk of HCC and mortality differ in patients with CHB treated with ETV and TDF.

Design We performed a retrospective cohort study of Veterans Affairs patients with CHB in the USA who initiated treatment with ETV or TDF between the dates of Food and Drug Administration approval of these medications and 1 January 2017. Multivariable Cox proportional hazards regression was used to determine the association between antiviral therapy and HCC risk as well as the risk of death or liver transplantation. Propensity score adjustment and competing risks analysis were performed.

Results We identified 2193 ETV-treated and 1094 TDF-treated patients who were followed for a mean of 5.4 years. We found no difference in the risk of HCC in ETV-treated versus TDF-treated patients (adjusted HR (aHR) 1.00, 95% CI 0.76 to 1.32). Results were similar in propensity score adjusted and competing risks analysis, and in multiple sensitivity analyses. We also found no difference in the risk of death or liver transplantation (aHR 1.16, 95% CI 0.98 to 1.39).

Conclusions We found no difference in the risk of HCC between patients with CHB treated with ETV versus TDF. Our results support current guideline recommendations that both agents are appropriate first-line options for the treatment of CHB.

  • hepatitis B
  • hepatobiliary cancer
  • hepatocellular carcinoma
  • liver

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  • Correction notice This article has been corrected since it published Online First. The author order has been amended.

  • Contributors FS conceptualisation, methodology, visualisation, writing of original draft, critical editing and review of final draft. KB formal analysis, methodology, visualisation, review of final draft. GNI supervision, conceptualisation, methodology, critical editing and review of final draft.

  • Funding The study was funded by a VA CSR&D grant I01CX001156 to GNI. FS was supported by NIH T32 grant 5T32DK007742-22.

  • Disclaimer The funding source played no role in study design, collection, analysis or interpretation of data. The contents do not represent the views of the US Department of Veterans Affairs or the US Government.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Institutional Review Board of the VA Puget Sound Healthcare System.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are deideintified participant data, available from KB ( and GNI ( on reasonable request.