Comparison of the on-treatment risks for hepatocellular carcinoma between entecavir and tenofovir: A propensity score matching analysis

J Gastroenterol Hepatol. 2020 Oct;35(10):1774-1781. doi: 10.1111/jgh.15031. Epub 2020 Mar 20.

Abstract

Background and aim: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) may reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). However, it is not clear whether there is difference in the on-treatment HCC risks between ETV and TDF.

Methods: In this retrospective cohort study, we compared the on-treatment HCC incidence of ETV and TDF in 1340 consecutive nucleos(t)ide analog-naïve CHB patients by propensity score (PS) matching analysis. PS was calculated by using age, sex, drinking history, diabetes, liver cirrhosis, hepatitis B e antigen positivity, hepatitis B virus DNA, hepatitis B s antigen titer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein, albumin, bilirubin, prothrombin time, platelet count, and calendar year of treatment initiation as covariates. The HCC risk was assessed by Cox regression with death and liver transplantation as competing risks in the 1:1 PS-matched cohorts (n = 596).

Results: TDF had higher cumulative virologic response (P = 0.027) whereas ETV showed higher AST and ALT normalization rates (P = 0.005 and < 0.001, respectively) in PS-matched cohorts. HCC risk was similar between ETV and TDF, either by PS-matching analysis (hazard ratio [HR] for TDF over ETV = 2.06, 95% confidence interval [CI] = 0.98-4.33, P = 0.058) or inverse probability of treatment weighting analysis (HR = 1.30, 95% CI = 0.81-2.10; P = 0.276).

Conclusions: ETV and TDF treatment was associated with similar risk for HCC development in CHB patients.

Keywords: entecavir; hepatocellular carcinoma; risk; tenofovir.

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects*
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology*
  • Cohort Studies
  • Female
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Propensity Score
  • Retrospective Studies
  • Risk
  • Tenofovir / adverse effects*

Substances

  • Antiviral Agents
  • entecavir
  • Guanine
  • Tenofovir