Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disease worldwide and is closely linked to systemic metabolic disorders. In addition to their classical role in hemostasis, platelets are increasingly recognized as active regulators of inflammation and immune responses, yet their contribution to MASLD pathogenesis remains incompletely defined. This review synthesizes current knowledge on how metabolic disturbances and gut microbiota dysbiosis trigger platelet hyperactivation and intrahepatic recruitment. We examined the mechanisms by which activated platelets exacerbate steatosis, amplify inflammation through interactions with immune cells, promote fibrogenic remodeling through hepatic stellate cell activation, and contribute to hepatocarcinogenesis. In the context of MASLD-associated hepatocellular carcinoma, platelet involvement may occur through both inflammation/fibrogenic remodeling–mediated and direct tumor-regulatory mechanisms. Furthermore, the therapeutic potential of antiplatelet agents, particularly aspirin, in attenuating disease progression has been evaluated. We conclude that targeting platelet-related pathways may represent a promising therapeutic strategy to interrupt the interplay between metabolic dysfunction and liver injury in MASLD.
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Juhee Ahn, Moon Haeng Hur, Hyunjae Shin, Min Kyung Park, Sungho Won, Jeayeon Park, Yunmi Ko, Youngsu Park, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
Clin Mol Hepatol 2026;32(1):339-352. Published online November 25, 2025
Background/Aims The association between aspirin use and hepatocellular carcinoma (HCC) risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study evaluated the effect of aspirin on HCC development in MASLD patients using Korean National Health Insurance Service (NHIS) and UK Biobank (UKB) databases.
Methods A retrospective cohort analysis was conducted using the NHIS database with a 3-year landmark design. Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) and 1:3 propensity score matching (PSM). Additionally, Mendelian randomization analysis was performed in the UKB cohort using a genomic risk score (GRS) for salicylic acid, based on genetic variants related to aspirin metabolism, as a proxy for aspirin use.
Results In the NHIS cohort, 6,584,155 eligible patients were included, of whom 1,723,435 had MASLD. After PSM, aspirin use was associated with a significantly lower risk of HCC compared to no aspirin use, in both the overall population (adjusted subdistribution hazard ratio [ASHR]=0.86; 95% confidence interval [CI] 0.78–0.95; P=0.002) and MASLD group (ASHR=0.86; 95% CI 0.75–0.99; P=0.036). Similar results were reproduced in the IPTW population and several sensitivity and subgroup analyses. In the UKB cohort, individuals in the top 95% of GRS had a significantly lower risk of HCC compared to those in the bottom 5%, in both the overall population (ASHR=0.61; 95% CI 0.39–0.95; P=0.028) and MASLD group (ASHR=0.47; 95% CI 0.29–0.76; P=0.002).
Conclusions Findings from both population-based and genetic analyses suggest a possible protective association between aspirin use and HCC in patients with MASLD, which warrants further validation.
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Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.
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Background/Aims This study was performed to determine whether low-dose aspirin and/or clopidogrel can induce gastrointestinal bleeding and gastroduodenal mucosal injury. Methods: A total of 387 patients who underwent coronary angiography at Seoul National University Bundang Hospital were assigned to one of three antiplatelet treatment groups: (1) control, (2) 100-mg enteric coated aspirin, and (3) 100-mg enteric coated aspirin plus clopidogrel. The incidences of gastroduodenal mucosal injury and gastrointestinal bleeding were prospectively evaluated, and risk factors for gastrointestinal bleeding were analyzed. Results: The rate of gastroduodenal mucosal injury was higher in the aspirin-plus-clopidogrel group than in the aspirin group (p=0.012), and higher in the aspirin group than in the control group (p=0.049). The rate of gastrointestinal bleeding was significantly higher in the aspirin-plus-clopidogrel group (9.4%) than in the control group (2.4%, p=0.048). The risk factors for gastrointestinal bleeding were older age (≥60 years) and the presence of at least two comorbid disorders. Conclusions: Low-dose enteric coated aspirin was found to be safe in patients with coronary artery disease, but the addition of clopidogrel increased the rate of gastrointestinal bleeding. Combined clopidogrel and aspirin should be used with caution in older patients having at least two comorbid conditions.
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