Tenofovir versus entecavir for hepatocellular Carcinoma prevention in an international consortium of chronic hepatitis B

Abstract

Background: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are among the recommended first‐line antiviral therapies for chronic hepatitis B (CHB). Whether they differ in their effectiveness in the prevention of hepatocellular carcinoma (HCC) development remains controversial. Methods: This was a retrospective cohort study based on analysis of the international REAL‐B (Real‐World Evidence from the Asia‐Pacific Rim Liver Consortium for HBV) consortium that encompassed 19 centers from 6 countries or regions. In this analysis, we identified previously untreated CHB patients who were then continuously treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within one year of therapy were excluded. Eligible patients were observed for HCC occurrence until December 23, 2018. The association between antiviral regimen and HCC risk was evaluated using competing‐risk survival regression. We also applied 1:1 propensity score matching (PSM) to balance the two treatment cohorts by baseline features. Results: A total of 5,537 patients met the inclusion and exclusion criteria (n= 4,837 received ETV and n=700 received TDF). Prior to PSM, the TDF cohort was significantly younger (mean age, 45.7 vs. 50.8 years; P<0.001) and had generally less severe liver diseases such as fewer patients with liver cirrhosis (18.7% vs. 27.8%; P<0.001) and higher platelet count (mean count, 196.8 vs. 178.8 103/μL; P<0.001). In the unadjusted analysis, TDF was associated with a lower risk of HCC (sub‐distribution hazard ratio [SHR], 0.45; 95% CI, 0.26~0.79; P=0.005) among all eligible patients. 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 differences in HCC incidences between the two matched cohorts (P=0.51) and no difference in the association between TDF or ETV, with HCC risk in the multivariable‐adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41~1.92; P=0.77). Conclusion: TDF and ETV did not significantly differ in the prevention of HCC in CHB patients. These findings suggest that both regimens may be considered similarly effective in the prevention of HCC.