Dear Editor,
I read with great interest the insightful response to my editorial on the recent article addressing “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis,” and I would like to express my appreciation to Prof. Hur, Prof. Shin and Prof. Kim for providing thoughtful and scientific insights into some concerns previously raised [
1-
3].
Ahn et al.’s important study suggests the potential preventive role of aspirin in hepatocellular carcinoma (HCC) among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) by employing multiple robust statistical approaches [
1]. In my editorial, I raised concerns regarding safety, optimal timing and duration of therapy, and appropriate patient selection [
2]. As acknowledged by the authors, these issues remain critical areas for future investigation and require more robust evidence before aspirin can be considered for the prevention of hepatocarcinogenesis in the MASLD population.
Importantly, the decision to use aspirin as an adjuvant therapy should be based on a careful balance between potential benefits and risks. In this context, several clinical guidelines have historically recommended initiating aspirin at around 50 years of age for the primary prevention of colorectal cancer. The U.S. Preventive Services Task Force (USPSTF) in 2016 recommended low-dose aspirin for the primary prevention of both cardiovascular disease and colorectal cancer in adults aged 50–59 years, provided that daily low-dose aspirin is taken for at least 10 years [
4]. However, the USPSTF revised its guidelines in 2022 and removed the recommendation for aspirin use in the primary prevention of colorectal cancer based on contradictory evidence [
5-
7]. These findings underscore the practical challenge of establishing strong evidence for adjuvant aspirin use while appropriately balancing its benefits and risks.
Nevertheless, numerous studies have demonstrated additional benefits of aspirin beyond the prevention of thromboembolic complications in cancer, including a reduced risk of cancer development and decreased metastatic spread [
8]. The potential mechanisms underlying the preventive and therapeutic effects of aspirin in cancer have been suggested to involve immune modulation, DNA repair pathways, regulation of cellular metabolism, anti-inflammatory effects, and antiplatelet activity [
9]. A recent study further demonstrated that aspirin may prevent metastasis by limiting platelet-derived thromboxane A
2 (TXA
2)–mediated suppression of T-cell immunity [
10].
Although many challenges remain to be addressed, the authors’ study contributes to a more nuanced understanding of aspirin’s potential role in MASLD-related hepatocarcinogenesis and stimulates future prospective studies. Finally, I would like to commend the authors for their efforts to address cancer prevention in patients with MASLD, which is an increasingly prevalent condition with no established preventive strategies, by integrating large population-based epidemiologic data with complementary genetic analyses.
FOOTNOTES
-
Conflicts of Interest
The author has no conflicts to disclose.
Abbreviations
metabolic dysfunction-associated steatotic liver disease
U.S. Preventive Services Task Force
REFERENCES
- 1. Ahn J, Hur MH, Shin H, Park MK, Won S, Park J, et al. Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis. Clin Mol Hepatol 2026;32:339-352.
- 2. Baek YH. Aspirin for hepatocellular carcinoma prevention in MASLD: How far are we ready to proceed?: Editorial on “Aspirin and HCC risk in MASLD: Nationwide cohort study with genetic risk analysis”. Clin Mol Hepatol 2026;32:1429-1432.
- 3. Hur MH, Shin H, Kim YJ. Correspondence to editorial 1 on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis”. Clin Mol Hepatol 2026;32:e378-e380.
- 4. Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 2016;164:836-845.
- 5. McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018;379:1519-1528.
- 6. McNeil JJ, Gibbs P, Orchard SG, Lockery JE, Bernstein WB, Cao Y, et al. Effect of aspirin on cancer incidence and mortality in older adults. J Natl Cancer Inst 2021;113:258-265.
- 7. Guirguis-Blake JM, Evans CV, Perdue LA, Bean SI, Senger CA. Aspirin use to prevent cardiovascular disease and colorectal cancer: updated evidence report and systematic review for the US preventive services task force. JAMA 2022;327:1585-1597.
- 8. Elwood P, Morgan G, Watkins J, Protty M, Mason M, Adams R, et al. Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against. Br J Cancer 2024;130:3-8.
- 9. Sun M, Yu J, Wan J, Dou X, Chen X, Ye F. Role of aspirin in cancer prevention. Cancer Treat Res Commun 2025;43:100884.
- 10. Yang J, Yamashita-Kanemaru Y, Morris BI, Contursi A, Trajkovski D, Xu J, et al. Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity. Nature 2025;640:1052-1061.
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