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Background: The aim of this study was to explore the impact of antiviral therapy (AVT) on short- and long-term outcomes after rehepatectomy for patients with recurrent hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Study Design: We analyzed data from 583 consecutive patients who underwent rehepatectomy for intrahepatic recurrence of HBV-related HCC after initial hepatectomy, between 2006 and 2011 at the Eastern Hepatobiliary Surgery Hospital. Tumor re-recurrence, recurrence to death survival (RTDS), and overall survival (OS) were compared using the Kaplan-Meier method and log-rank test. The independent risk factors of prognoses were analyzed using the Cox proportional hazards model. Postoperative viral reactivation, surgical morbidity, and mortality were also observed.Results: Preoperative AVT reduced viral reactivation rate after rehepatectomy (5.8% for AVT patients, 16.3% and 16.6% for non-AVT patients with viral level ≤ or >2,000 IU/mL, respectively; p ≤ 0.028). Viral reactivation and non-AVT were independent risk factors of tumor re-recurrence (hazard ratios 1.446 and 1.778, respectively), RTDS (1.691 and 2.457, respectively), and OS (1.781 and 1.857, respectively). The AVT improved long-term outcomes as compared with non-AVT with a viral level of ≤ or >2,000 IU/mL (5-year re-recurrence rate: 69% vs 81% vs 96%, respectively; 5-year RTDS rate: 47% vs 27% vs 17%, respectively; all p ≤ 0.016). Pre- plus postoperative AVT achieved a better 5-year OS rate than postoperative AVT alone (83% vs 60%; p = 0.045); there were insignificant differences in 5-year re-recurrence and RTDS rates (61% vs 77%, p = 0.102; 50% vs 44%, p = 0.395).Conclusions: Preoperative AVT decreased viral reactivation rate, and AVT initiated either before or after rehepatectomy contributed to better long-term prognoses after rehepatectomy for recurrent HBV-related HCC. [ABSTRACT FROM AUTHOR]