Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis.
aspirin
hepatocellular carcinoma
liver resection
metformin
statin
survival
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
22
08
2023
received:
26
11
2022
accepted:
11
09
2023
medline:
23
10
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHOD
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.
RESULTS
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.
CONCLUSION
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.
Identifiants
pubmed: 37737550
doi: 10.1002/cam4.6569
pmc: PMC10587989
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Metformin
9100L32L2N
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19548-19559Informations de copyright
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Dig Dis Sci. 2008 Nov;53(11):2989-94
pubmed: 18363104
PLoS One. 2021 Mar 4;16(3):e0247231
pubmed: 33661912
Am J Gastroenterol. 2012 Jan;107(1):46-52
pubmed: 22085817
PLoS One. 2015 Jun 01;10(6):e0127967
pubmed: 26030161
Eur J Gastroenterol Hepatol. 2020 Aug;32(8):1030-1035
pubmed: 31764404
Leukemia. 2002 Apr;16(4):508-19
pubmed: 11960327
J Gastrointest Surg. 2021 May;25(5):1193-1202
pubmed: 32378092
Eur J Epidemiol. 2013 Jun;28(6):485-92
pubmed: 23681775
JAMA Oncol. 2018 Dec 1;4(12):1683-1690
pubmed: 30286235
Anticancer Res. 2019 Oct;39(10):5639-5643
pubmed: 31570461
Cancer. 2016 Nov 15;122(22):3430-3446
pubmed: 27622302
J Hepatol. 2018 Mar;68(3):526-549
pubmed: 28989095
Nat Med. 2005 Nov;11(11):1167-9
pubmed: 16258538
Liver Int. 2018 Nov;38(11):2018-2027
pubmed: 29956875
Eur J Cancer Prev. 2022 Jan 1;31(1):35-43
pubmed: 33470689
Surgery. 2018 Feb;163(2):264-269
pubmed: 29167018
BMC Cancer. 2021 Jan 15;21(1):70
pubmed: 33446127
Biosci Trends. 2017 Nov 20;11(5):574-580
pubmed: 29081488
Ann Surg Oncol. 2016 Dec;23(Suppl 5):874-883
pubmed: 27541812
Front Pharmacol. 2022 Mar 01;13:764854
pubmed: 35300300
Medicine (Baltimore). 2016 Sep;95(36):e4639
pubmed: 27603355
Am J Med Sci. 2011 Apr;341(4):301-4
pubmed: 21441859
Hepatology. 2016 Jul;64(1):47-57
pubmed: 26891205
Pharmacol Rev. 2012 Jan;64(1):102-46
pubmed: 22106090
J Clin Oncol. 2013 Apr 20;31(12):1514-21
pubmed: 23509319
Medicine (Baltimore). 2016 Apr;95(17):e3527
pubmed: 27124061
Liver Int. 2017 Mar;37(3):434-441
pubmed: 27775209
Transplant Proc. 2010 Nov;42(9):3823-7
pubmed: 21094864
Ann Surg. 2015 Mar;261(3):521-6
pubmed: 24950265
N Engl J Med. 2019 Apr 11;380(15):1450-1462
pubmed: 30970190
Int J Cancer. 2017 Feb 15;140(4):798-806
pubmed: 27861855
Ann Hepatol. 2020 May - Jun;19(3):320-328
pubmed: 31980358
Cancer Res. 2010 Oct 1;70(19):7699-709
pubmed: 20876807
Front Immunol. 2021 Feb 02;11:586760
pubmed: 33603734
Pharmacol Res. 2020 Sep;159:104982
pubmed: 32502639
Cancers (Basel). 2020 Mar 13;12(3):
pubmed: 32183029
Cancer Res. 2011 Jul 1;71(13):4366-72
pubmed: 21540236
Curr Cancer Drug Targets. 2005 Dec;5(8):579-94
pubmed: 16375664
Nat Rev Clin Oncol. 2013 Nov;10(11):625-42
pubmed: 24080598
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934
pubmed: 24239923
Nat Med. 2019 Apr;25(4):641-655
pubmed: 30936549
Cell Signal. 2021 Nov;87:110122
pubmed: 34438015
Clin Cancer Res. 2003 Jan;9(1):10-9
pubmed: 12538446
Hepatobiliary Surg Nutr. 2021 Aug;10(4):454-463
pubmed: 34430524
Surgery. 2015 Mar;157(3):454-62
pubmed: 25633732
BMJ Open. 2014 Sep 16;4(9):e005399
pubmed: 25227628
Diabetologia. 2017 Sep;60(9):1639-1647
pubmed: 28776080
Clin Cancer Res. 2011 Jun 15;17(12):3993-4005
pubmed: 21543517
Cancer Med. 2023 Oct;12(19):19548-19559
pubmed: 37737550
Ann Surg. 2011 Mar;253(3):453-69
pubmed: 21263310
Updates Surg. 2016 Jun;68(2):191-7
pubmed: 27164985
BMC Cancer. 2022 Jan 21;22(1):91
pubmed: 35062904