Aspirin and Nonsteroidal Anti-inflammatory Drug Applications in Hepatocellular Carcinoma Management

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) exert antineoplastic effects in hepatocellular carcinoma (HCC) primarily through cyclooxygenase inhibition, leading to reduced prostaglandin synthesis, modulation of inflammatory cascades and attenuation of platelet–tumour interactions. Epidemiological evidence indicates that long-term aspirin use in high-risk cohorts can lower HCC incidence and overall mortality without a significant increase in major bleeding. Mechanistic studies in cellular and animal models reveal that aspirin and select NSAIDs downregulate immunosuppressive ligands such as PD-L1, reprogramme the tumour microenvironment and can synergise with targeted therapies, including sorafenib, to suppress tumour growth and metastasis. These findings underscore the global potential of aspirin and related agents as cost-effective chemopreventive and adjuvant adjuncts in HCC management, while ongoing research seeks to optimise dosing strategies and delineate patient subgroups most likely to benefit.

Research from Nature Portfolio

In rodent models of chemically induced HCC, aspirin administration significantly reduced tumour number and liver weight ratio by attenuating inflammatory mediators and inhibiting PD-L1 expression. These interventions enhanced CD4+ T-cell infiltration, decreased CD8+ lymphocyte exhaustion and ameliorated biochemical markers of liver injury, thereby limiting fibrotic encapsulation around neoplastic nodules. Separately, a large population-based cohort study in a region endemic for viral hepatitis demonstrated that regular aspirin consumption correlated with a dose-dependent reduction in HCC risk, with combined NSAID use yielding additive protective effects. Together, these studies integrate mechanistic insight and real-world epidemiology to validate the role of aspirin in HCC prevention and immunomodulation.

Aspirin and Nonsteroidal Anti-inflammatory Drug Applications in Hepatocellular Carcinoma Management publication trend

The graph below shows the total number of articles in aspirin and nonsteroidal anti-inflammatory drug applications in hepatocellular carcinoma management across all publications each year (not limited to Nature Index journals).

Technical terms

Cyclooxygenase (COX): Enzyme family (COX-1 and COX-2) responsible for prostaglandin synthesis and platelet aggregation, inhibited by aspirin and NSAIDs.

Programmed death ligand-1 (PD-L1): Immune checkpoint protein on tumour cells that binds PD-1 on T cells to suppress antitumour immunity.

Propensity score matching: Statistical method used in observational studies to balance baseline characteristics between treated and control groups and reduce confounding.

Tumour microenvironment: The surrounding stromal cells, immune infiltrates, extracellular matrix and signalling molecules that influence tumour behaviour.

References

1. Daily Aspirin Reduced the Incidence of Hepatocellular Carcinoma and Overall Mortality in Patients with Cirrhosis. Cancers (2023).
2. Hepatoprotective effects of aspirin on diethylnitrosamine-induced hepatocellular carcinoma in rats by reducing inflammation levels and PD-L1 expression. Scientific Reports (2023).
3. Aspirin Use and Risk of Hepatocellular Carcinoma in a National Cohort Study of Korean Adults. Scientific Reports (2018).
4. Aspirin Minimized the Pro-Metastasis Effect of Sorafenib and Improved Survival by Up-Regulating HTATIP2 in Hepatocellular Carcinoma. PLOS ONE (2013).
5. Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study. BMC Gastroenterology (2020).
6. Antiplatelet Therapy Improves the Prognosis of Patients with Hepatocellular Carcinoma. Cancers (2020).