Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany.
Cancer Med. 2023 Oct;12(19):19548-19559. doi: 10.1002/cam4.6569. Epub 2023 Sep 22.
Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear.
Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence-free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed.
Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non-metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers.
Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.
他汀类药物、二甲双胍和阿司匹林已被报道可降低肝细胞癌(HCC)的发生率。然而,其在根治性肝切除术后对 HCC 患者生存结局的影响仍不清楚。
共纳入 353 例首次诊断为 HCC 并接受根治性肝切除术的患者。对每种药物(他汀类药物、二甲双胍和阿司匹林)进行倾向评分匹配的用户:非用户比例为 1:2。评估总生存期(OS)和无复发生存期(RFS),并进行多变量 Cox 比例风险分析。
62 例患者接受他汀类药物治疗,48 例患者使用二甲双胍,53 例患者在术前至少 90 天开始使用阿司匹林。这些药物均未改善 OS。在匹配队列中,他汀类药物使用者的 RFS 明显长于非使用者(p=0.021)。亲水性他汀类药物使用者的 RFS 明显长于非使用者,而疏水性他汀类药物使用者则不然。多变量分析显示,他汀类药物的使用显著改善了 RFS(风险比[HR]:0.41,95%置信区间[CI]:0.17-0.97,p=0.044)。二甲双胍使用者与非使用者的 RFS 无差异。在糖尿病患者中,在匹配队列中,二甲双胍使用者的 RFS 长于非二甲双胍使用者(84.1% vs. 60.85%,p=0.069)。阿司匹林使用者与非使用者之间的术后 RFS 无差异。
HCC 患者术前使用他汀类药物可增加根治性肝切除术后的 RFS,但二甲双胍和阿司匹林与改善生存无关。需要进行随机对照试验来证实本研究的结果。