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他汀类药物在肝癌患者接受肝移植中的抗肿瘤作用。

Anticancer Effect of Statins in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

机构信息

Division of HepatologyDepartment of Internal MedicineCollege of Medicine The Catholic University of Korea Seoul Republic of Korea The Catholic Liver Research CenterCollege of Medicine The Catholic University of Korea Seoul Republic of Korea Department of SurgeryCollege of Medicine The Catholic University of Korea Seoul Republic of Korea.

出版信息

Liver Transpl. 2022 Mar;28(3):397-406. doi: 10.1002/lt.26258. Epub 2021 Aug 29.

Abstract

The anticancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC. Consecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effects of statins on HCC recurrence and mortality were compared between statin user and statin nonuser groups. We performed the analyses in a variety of ways, including inverse probability treatment weighting (IPTW) methods to balance any confounders and the landmark method to avoid immortal time bias. A total of 430 patients were enrolled, among whom 323 (75.1%) were statin nonusers and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1-122.6 months) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was a predictor of HCC recurrence (adjusted hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.1-0.6; P = 0.002), all-cause mortality (adjusted HR, 0.3; 95% CI, 0.2-0.5; P < 0.001), and HCC-related mortality (adjusted HR, 0.4; 95% CI, 0.2-0.9; P = 0.03). The effects of statin use on clinical outcomes were also identified through IPTW analysis. There was a dose-dependent relationship between statin use and HCC recurrence. The anticancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. Statin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

摘要

他汀类药物的抗癌作用引起了关注。然而,目前尚不清楚他汀类药物的使用是否会降低因肝细胞癌(HCC)而行肝移植(LT)患者的 HCC 复发风险。本研究纳入了 1995 年至 2019 年间因 HCC 行 LT 的连续患者。比较了他汀类药物使用者和非使用者两组患者的 HCC 复发和死亡率。我们通过各种方法进行了分析,包括逆概率治疗加权(IPTW)方法来平衡任何混杂因素,以及里程碑方法来避免不朽时间偏倚。共纳入 430 例患者,其中 323 例(75.1%)为他汀类药物非使用者,107 例(24.9%)为他汀类药物使用者。在中位随访 64.9 个月(IQR,26.1-122.6 个月)期间,79 例患者(18.4%)发生 HCC 复发,111 例患者(25.8%)死亡。在死亡患者中,53 例(47.7%)为 HCC 相关死亡。他汀类药物的使用是 HCC 复发的预测因素(调整后的危险比[HR],0.3;95%置信区间[CI],0.1-0.6;P=0.002)、全因死亡率(调整后的 HR,0.3;95%CI,0.2-0.5;P<0.001)和 HCC 相关死亡率(调整后的 HR,0.4;95%CI,0.2-0.9;P=0.03)。通过 IPTW 分析也确定了他汀类药物使用对临床结果的影响。他汀类药物的使用与 HCC 复发之间存在剂量依赖性关系。他汀类药物对 HCC 复发的抗癌作用在多变量分层和敏感性分析中始终具有显著意义。他汀类药物的使用显著降低了 HCC 复发的风险,改善了因 HCC 而行 LT 患者的生存率。

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