Antiviral Therapy Influences Short-term And Long-term Prognosis After Repeated Hepatectomy For Recurrent HBV-related Hepatocellular Carcinoma

Objective:Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second leading cause of cancer-related death worldwide. Hepatitis B virus (HBV) infection is the main causative factor of HCC, especially in the majority of Asian and African regions. High HBV deoxyribonucleic acid (HBV DNA) level has been reported to be an important risk factor for disease development.The aim of this study is to explore the effects antiviral therapy (AVT) on short-and long-term outcomes of patients who underwent re-hepatectomy for intrahepatic recurrent HBV-related hepatocellular carcinoma (HBV-HCC).Methods:Between 2002 and 2011,a total of 595 HBV-related HCC patients who underwent re-hepatectomy were included at the EHBH and a database was established. After exclusion,559 patients were included to analyze the perioperative surgical complications including mobidity and motality.538 patients were included for analyzing the impact of preopetative-AVT on the mobidity of HBV-related complications (perioperative HBV reactivation, liver hepatitis, and liver failure).Based on preoperative viral level, and whether accepted AVT,538 patients were divided into Preoperative-AVT group (n=69), Non-preoperative-AVT-low group (n=191) and Non-preoperative-AVT-high (n=178), and the tumor re-recurrence and recurrence-to-death survival (RTDS) were observed and compared between the groups. Then 481 patients were included for analyzing the impact of preoperative HBV DNA level and AVT on the long-term prognosis. Based on the different viral levels,481 patients were divided into high viral level (n=285) and low viral level (n=196). Based on whether AVT was accepted and viral level,481 patients were divided into AVT-high (n=86), AVT-low (n=53), Non-AVT-high (n=199) and Non-AVT-low (n=143), and the tumor re-recurrence and recurrence-to-death survival were observed and compared between the groups. Based on the start and duration of the AVT, 481 patients were divided into Non-AVT group (n=342), Pre-&postoperative-AVT group (n=66), and Postoperative-AVT group (n=73), and the tumor re-recurrence and recurrence-to-death survival were observed and compared between the groups. In the baseline characteristics of the study, the continuous variables were expressed as mean ± standard deviation, and the categorical variables as the numbers and percentage. The Mann-Whitney U-test was used to compare measurement data, and the chi-square test was used to analyze enumeration data. Cumulative re-recurrence and survival rates were calculated by the Kaplan-Meier method, and the differences were compared by the log-rank test. The Cox proportional hazards model was applied to analyze post-re-hepatectomy prognosis, and categorical variables were used in univariate and multivariate analysis. Statistical significance was defined as P<0.05 at both sides. All statistical analyses were performed by using SPSS version 19.0(SPSS, Chicago, IL, USA).Results:The 5-year re-recurrence and RTDS rates of patients with pre-re-hepatectomy viral level> or≤2000 IU/ml (n=279 and 202) were 94% vs.74% and 12% vs.29%, respectively (all P<0.001). Viral level> 2000 IU/ml was an independent risk factor for these prognostic measurements in the whole cohort (Hazard Ratio and 95% confidence interval:1.649,1.095-2.483; 1.674,1.078-2.599). AVT decreased re-recurrence and improved postoperative survival for cirrhotic patients with low or high viral level(all P<0.001), but only decreased re-recurrence and improved postoperative survival for non-cirrhotic patients with high viral level (all P<0.001).For non-cirrhotic patients with low viral level, only re-recurrence rates were decreased significantly(P=0.015). In the non-AVT, pre-&postoperative-AVT and postoperative-AVT groups, the 5-year re-recurrence rates were 92% vs.53% vs.76%, respectively (all P<0.001); RTDS rates were 14%vs.50% vs.29%, respectively (all P< 0.047).Conclusions:The pre-re-hepatectomy viral level had significant impacts on re-recurrence and long-term survival of patients with HBV-related recurrent HCC who underwent re-hepatectomy, and the implementation of pre-and post-reoperative AVT could evidently improve surgical prognosis. Patients should receive AVT regardless of viral level and cirrhosis.