Tenofovir versus entecavir on the prognosis of hepatitis B-related hepatocellular carcinoma after surgical resection: a randomised controlled trial

Background: Nucleot(s)ide analog treatment (entecavir (ETV) and tenofovir (TDF)) is reported to be associated with decreased tumor recurrence and death in HBV-related hepatocellular carcinoma (HCC) patients, yet further work is needed to evaluate the different efficacies of these two agents on the prognosis of early-stage HBV-related HCC patients after curative liver resection. Material and methods: From July 2017 to January 2019, 148 patients with HBV-related HCC who underwent curative liver resection were randomized to receive TDF (n=74) or ETV (n=74) therapy. The primary end point was tumor recurrence in the intention-to-treat (ITT) population. Overall survival (OS) and tumor recurrence of patients were compared by multivariable-adjusted Cox regression and competing risk analyses. Results: During the follow-up with continued antiviral therapy, 37 (25.0%) patients developed tumor recurrence, and 16 (10.8%) patients died (N=15) or received liver transplantation (N=1). In the ITT cohort, the recurrence-free survival for the TDF group was significantly better than that for the ETV group ( P =0.026). In the multivariate analysis, the relative risks of recurrence and death/liver transplantation for ETV therapy were 3.056 (95% confidence interval (CI): 1.015-9.196; P =0.047) and 2.566 (95% CI: 1.264-5.228; P =0.009), respectively. Subgroup analysis of the PP population indicated a better OS and RFS of patients receiving TDF therapy ( P =0.048; HR =0.362; 95% CI: 0.132-0.993 and P =0.014; HR =0.458; 95% CI: 0.245-0.856). Additionally, TDF therapy was an independent protective factor against late tumor recurrence ( P =0.046; hazard ratio (HR)=0.432; 95% CI: 0.189-0.985) but not against early tumor recurrence ( P =0.109; HR =1.964; 95% CI: 0.858-4.494). Conclusion: HBV-related HCC patients treated with consistent TDF therapy had a significantly lower risk of tumor recurrence than those treated with ETV after curative treatment.