核苷类似物与肝切除术后乙型肝炎病毒相关肝细胞癌复发的风险之间的关联。
Association between nucleoside analogues and risk of hepatitis B virus–related hepatocellular carcinoma recurrence following liver resection.
机构信息
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
出版信息
JAMA. 2012 Nov 14;308(18):1906-14. doi: 10.1001/2012.jama.11975.
CONTEXT
Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection.
OBJECTIVE
To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery.
DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010.
MAIN OUTCOME MEASURES
The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality.
RESULTS
The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).
CONCLUSION
Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.
背景
肿瘤复发是接受根治性肝切除术后肝细胞癌（HCC）患者的主要问题。
目的
研究核苷类似物的使用与乙型肝炎病毒（HBV）相关 HCC 患者根治性手术后肿瘤复发风险之间的关系。
设计、地点和参与者：这是一项 2003 年 10 月至 2010 年 9 月期间开展的全国性队列研究，数据来自台湾全民健康保险研究数据库。在 100938 例新诊断 HCC 患者中，我们确定了 4569 例接受 HCC 根治性肝切除术的 HBV 相关 HCC 患者。
主要结局测量
比较未接受核苷类似物治疗的患者（未治疗组，n = 4051）和接受核苷类似物治疗的患者（治疗组，n = 518）的首次肿瘤复发风险。在调整竞争死亡率后，计算累积发生率和风险比（HR）。
结果
与未治疗组相比，治疗组的肝硬化发生率更高（48.6% vs 38.7%；P <.001），但 HCC 复发风险较低（n = 106 [20.5%] vs n = 1765 [43.6%]；P <.001），总死亡率较低（n = 55 [10.6%] vs n = 1145 [28.3%]；P <.001）。在调整竞争死亡率后，治疗组 HCC 复发的 6 年累积发生率显著降低（45.6%；95%CI，36.5%-54.6% vs 未治疗组，54.6%；95%CI，52.5%-56.6%；P <.001）。治疗组的 6 年总死亡率为 29.0%（95%CI，20.0%-38.0%），未治疗组为 42.4%（95%CI，40.0%-44.7%；P <.001）。在改良 Cox 回归分析中，核苷类似物使用（HR，0.67；95%CI，0.55-0.81；P <.001）、他汀类药物使用（HR，0.68；95%CI，0.53-0.87；P =.002）和非甾体抗炎药或阿司匹林使用（HR，0.80；95%CI，0.73-0.88；P <.001）与 HCC 复发风险降低独立相关。多变量分层分析证实了所有亚组患者的相关性，包括非肝硬化（HR，0.56；95%CI，0.42-0.76）和糖尿病患者（HR，0.52；95%CI，0.31-0.89）。
结论
核苷类似物的使用与 HBV 相关 HCC 患者肝切除术后 HCC 复发风险降低相关。
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