Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea.
Liver Int. 2023 Sep;43(9):2017-2025. doi: 10.1111/liv.15653. Epub 2023 Jun 27.
Statins have been reported to reduce overall death and hepatocellular carcinoma (HCC) recurrence in liver transplantation (LT) recipients. However, previous retrospective studies have significant flaws in immortal time bias.
Using data from 658 patients who received LT for HCC, we matched 140 statin users with statin nonusers in a 1:2 ratio at the time of the first statin administration after LT using the exposure density sampling (EDS). The propensity score, calculated using baseline variables (including explant pathology), was used for EDS to equilibrate both groups. HCC recurrence and overall death were compared after adjusting for information at the time of sampling.
Among statin users, the median time to statin start was 219 (IQR 98-570) days, and intensity of statins was mainly moderate (87.1%). Statin users and nonusers sampled using EDS showed well-balanced baseline characteristics, including detailed tumour pathology, and similar HCC recurrence with cumulative incidences of 11.3% and 11.8% at 5 years, respectively (p = .861). In multivariate Cox models (HR 1.04, p = .918) and subgroup analyses, statins did not affect HCC recurrence. Conversely, statin users showed a significantly lower risk of overall death than nonusers (HR 0.28, p < .001). There was no difference in the type and intensity of statin usage between statin users who experienced HCC recurrence and those who did not.
Upon controlling immortal time bias by EDS, statins did not affect HCC recurrence but reduced mortality after LT. Statin usage is encouraged for survival benefits but not for preventing HCC recurrence in LT recipients.
他汀类药物已被报道可降低肝移植（LT）受者的总死亡率和肝细胞癌（HCC）复发率。然而，之前的回顾性研究在无事件时间偏倚方面存在显著缺陷。
我们使用了 658 例因 HCC 接受 LT 的患者的数据，在 LT 后首次使用他汀类药物时，使用暴露密度抽样（EDS）以 1:2 的比例将 140 例他汀类药物使用者与他汀类药物非使用者进行匹配。使用基线变量（包括移植前病理学）计算倾向评分，用于 EDS 来平衡两组。在调整采样时的信息后，比较 HCC 复发和总死亡率。
在他汀类药物使用者中，开始使用他汀类药物的中位时间为 219（IQR 98-570）天，他汀类药物的强度主要为中等（87.1%）。使用 EDS 抽样的他汀类药物使用者和非使用者显示出良好平衡的基线特征，包括详细的肿瘤病理学，并且 5 年时的 HCC 累积发生率分别为 11.3%和 11.8%，差异无统计学意义（p=0.861）。在多变量 Cox 模型（HR 1.04，p=0.918）和亚组分析中，他汀类药物并未影响 HCC 复发。相反，与非使用者相比，他汀类药物使用者的总死亡率明显降低（HR 0.28，p<0.001）。在经历 HCC 复发和未经历 HCC 复发的他汀类药物使用者中，他汀类药物的类型和强度没有差异。
通过 EDS 控制无事件时间偏倚后，他汀类药物并未影响 HCC 复发，但降低了 LT 后的死亡率。建议使用他汀类药物以提高生存率，但不能用于预防 LT 受者的 HCC 复发。
