Tenofovir Versus Entecavir on Recurrence of Hepatitis B Virus–Related Hepatocellular Carcinoma After Surgical Resection

Background and Aims Studies have suggested that tenofovir disoproxil fumarate (TDF) treatment is associated with a significantly lower risk of hepatocellular carcinoma (HCC) occurrence when compared with entecavir (ETV) therapy in patients with chronic hepatitis B. We aimed to compare HCC recurrence and survival of patients treated with TDF or ETV after surgical resection for hepatitis B virus (HBV)–related HCC. Approach and Results This historical cohort study included 1,695 consecutive patients treated with ETV (n = 813) or TDF (n = 882) after curative‐intent hepatectomy for HBV‐related HCC of Barcelona Clinic Liver Cancer stage 0 or A in Korea between 2010 and 2018. HCC recurrence and overall survival of patients were compared between ETV and TDF groups by propensity score–matched and multivariable‐adjusted Cox regression analyses from the date of hepatectomy for HCC. The mean age of the study patients was 54.8 years, and 1,294 patients (76.3%) were male. During the median follow‐up duration of 37.6 months with continued ETV or TDF therapy, 561 (33.1%) patients developed HCC recurrence, 144 (8.4%) died, and 22 (1.3%) received liver transplant. Compared with ETV, TDF therapy was associated with significantly higher recurrence‐free ( P = 0.02) and overall survival ( P = 0.03) rates by propensity score–matched analysis. By multivariable‐adjusted analysis, the TDF group was associated with significantly lower rates of HCC recurrence (hazard ratio [HR], 0.82; 95% confidence interval, 0.68‐0.98; P = 0.03), and death or transplantation (HR, 0.62; 95% confidence interval, 0.44‐0.88; P = 0.01). TDF therapy was an independent protective factor for both early (<2 years; HR, 0.79; P = 0.03) and late (≥2 years; HR, 0.68; P = 0.03) postoperative HCC recurrence. Conclusions Among patients who underwent curative hepatectomy for HBV‐related HCC, TDF therapy was associated with a significantly lower risk of HCC recurrence and better overall patient survival compared with ETV therapy.