Cho H, Ahn H, Lee D H, Lee J-H, Jung Y J, Chang Y, Nam J Y, Cho Y Y, Lee D H, Cho E J, Yu S J, Lee J M, Kim Y J, Yoon J-H
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
J Viral Hepat. 2018 Jun;25(6):707-717. doi: 10.1111/jvh.12855. Epub 2018 Feb 6.
Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.
核苷(酸)类似物(NAs)已被证明可降低肝细胞癌(HCC)复发风险。本研究评估了高效能NAs(恩替卡韦和替诺福韦酯富马酸盐[TDF])在根治性治疗乙型肝炎病毒(HBV)相关HCC后,是否比低效能NAs更有效地降低肿瘤复发风险。本研究纳入了607例连续接受手术切除或射频消融治疗的HBV相关HCC患者。根据抗病毒治疗情况将患者分为三组:A组(未接受抗病毒治疗;n = 261)、B组(低效能NA;n = 90)和C组(高效能NA;n = 256)。主要终点是无复发生存期(RFS)。在随访期间,A组、B组和C组的中位RFS分别为29.4个月、25.1个月和88.2个月(P <.001,对数秩检验)。多因素Cox分析表明,C组的RFS显著长于A组(调整后风险比[HR] = 0.39,P <.001)和B组(调整后HR = 0.47,P <.001)。当使用逆概率加权使基线特征平衡时,C组的RFS仍显著长于A组(调整后HR = 0.46,P <.001)和B组(调整后HR = 0.59,P =.007)。C组的病毒突破风险显著低于B组(HR = 0.19,P <.001)。病毒突破是B组和C组中RFS较短的独立危险因素(调整后HR = 2.03,P =.007,时间依赖性Cox分析)。与其他抗病毒药物和未进行抗病毒治疗相比,具有高耐药基因屏障的抗病毒药物(恩替卡韦和TDF)可降低HCC复发风险,尤其是在基线病毒载量高的患者中。