Tenofovir Versus Entecavir for Hepatocellular Carcinoma Prevention in an International Consortium of Chronic Hepatitis B

Am J Gastroenterol. 2020 Feb;115(2):271-280. doi: 10.14309/ajg.0000000000000428.


Introduction: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).

Methods: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases.

Results: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77).

Discussion: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / prevention & control*
  • China
  • Cohort Studies
  • Disease Progression
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Hong Kong
  • Humans
  • International Cooperation
  • Japan
  • Liver Neoplasms / etiology
  • Liver Neoplasms / prevention & control*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Republic of Korea
  • Retrospective Studies
  • Taiwan
  • Tenofovir / therapeutic use*
  • Treatment Outcome
  • United States


  • Antiviral Agents
  • entecavir
  • Guanine
  • Tenofovir