Although studies have compared the use of tenofovir disoproxil fumarate (TDF) with entecavir (ETV) in patients with chronic hepatitis B (CHB), further evidence of superiority of one treatment over the other is needed before making changes in practice, according to a review published in Gastroenterology.1

A previous retrospective study demonstrated that TDF was associated with a lower risk of HCC compared with ETV in a general cohort of 29,350 patients.1,2 It was a well-designed study that accounted for the substantial differences in several variable of the 2 groups of patients by using a 1:5 propensity score matching analysis and thus found consistent results. 

However, this study had several issues including that the number of patients in the TDF group (n=1309) was much smaller compared with the ETV group (n=28,041). At total of 8 patients in the TDF group developed HCC, compared with 1386 patients in the ETV group. In addition, this study has some notable differences compared with other studies that evaluated ETV and TDF. For example, the number of patients with cirrhosis was substantially lower in this study compared with other studies,1-5 which can affect the results as presence of cirrhosis in CHB increases the risk for HCC. A strength of this study, however, was the inclusion of patients with decompensated cirrhosis, which are often excluded in other studies.1,2

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The investigators concluded that, “Both ETV and TDF are commonly used in treatment of CHB and proving superiority of one treatment over the other may lead to widespread

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changes in practice.”1 They added that, “Given that a randomized controlled trial (RCT) to evaluate these outcomes may not be feasible, more concrete evidence of superiority of one treatment over the other from high quality and multicenter observational studies including both compensated and decompensated cirrhosis patients is required before making any changes in practice.”


  1. Kamal F, Khan MA. Is tenofovir associated with lower risk of hepatocellular carcinoma in patients with chronic hepatitis B compared to entecavir [published online March 19, 2020]? Gastroenterology. doi:10.1053/j.gastro.2020.02.062
  2. Yip TC-F, Wong VW-S, Chan HL-Y, et al. Tenofovir is associated with lower risk of hepatocellular carcinoma than entecavir in patients with chronic HBV infection in China. Gastroenterology. 2020;158(1):215-225.e6.
  3. Hsu YC, Wong GL, Chen CH, et al. Tenofovir versus entecavir for hepatocellular carcinoma prevention in an international consortium of chronic hepatitis B [published online October 11, 2019]. Am J Gastroenterol. doi:10.14309/ajg.0000000000000428
  4. Kim BG, Park NH, Lee SB, et al. Mortality, liver transplantation and hepatic complications in patients with treatment-naïve chronic hepatitis B treated with entecavir vs tenofovir. J Viral Hepat. 2018;25:1565-1575.
  5. Kim SU, Seo YS, Lee HA, et al. A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naïve chronic hepatitis B in South Korea. J Hepatol. 2019;71(3):456-464.