Aspirin, NSAID Use Linked to Lower Cancer, Mortality Risk in Chronic Liver Diseases

Exposure to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with a reduced risk of cancer, including liver cancer, and overall mortality in patients with chronic liver diseases, according to findings from a recent study.1

Results from the population-based cohort study of inpatients and outpatients with chronic liver diseases in Sweden suggest a significant risk reduction in overall cancer incidence and mortality with aspirin or NSAID use, even after taking comorbidities and the severity of the liver disease into account.1

“To the best of our knowledge, this is the first study demonstrating a reduced cancer risk among patients with liver diseases exposed to aspirin and NSAIDs,” Knut Stokkeland, of the Stockholm Centre for Dependency Disorders and the department of clinical neuroscience at Karolinska Institutet in Sweden, and colleagues wrote.1

According to the American Liver Foundation, more than 100 million people in the US have some form of liver disease which, left untreated, can lead to liver failure and liver cancer.2 Given the role that inflammation plays in the progression of chronic liver diseases, anti-inflammatory drugs may be beneficial for these patients, although aspirin and NSAIDs are currently widely viewed as harmful for patients with liver disease.1

To explore the effects of exposure to anti-inflammatory drugs on the risk of adverse liver events, cancers, and mortality in patients with chronic liver diseases, investigators conducted a population-based cohort study of inpatients and outpatients between July 2005 and December 2020 using the Patient Register at the Swedish Board of Health and Welfare. They additionally searched the database for primary care in the central healthcare utilization data warehouse at the Stockholm Center for Health Data during the same period, merging the 2 registers to create a single primary cohort.1

Investigators then collected data on all prescribed dispensed drugs from the Swedish Prescribed Drug Registry during the study period for aspirin; NSAIDs; antivirals; antibiotics; immunosuppressants; and glucocorticoids. Exposure to a drug was defined as ≥ 2 dispensations after the patient had been diagnosed with a liver disease. Exposure time was calculated from the first dispensation.1

In total, the study cohort comprised 21,439 patients, the majority of whom had alcohol-associated liver disease (ALD; n = 9472), viral hepatitis (n = 7731), and autoimmune hepatitis (n = 493).1

During 147,065.3 patient-years of follow-up, 10,279 (47.9%) patients died. Investigators noted more than half (51.1%) of patients with ALD died during the study period. Additionally, they pointed out the number of patients who developed any cancer was highest among those with primary biliary cholangitis (41.4%), and the greatest proportion of liver cancers was observed in patients with ALD (8.3%).1

Results showed exposure to aspirin, NSAIDs, antivirals, and immunosuppressants was associated with a reduced risk for mortality, with the largest reduction in the crude hazard rate observed in patients exposed to NSAIDs (crude hazard ratio [cHR], 0.64; 95% CI, 0.61–0.68, P <.001). Of note, exposure to aspirin was also associated with a reduction in mortality risk (cHR, 0.92; 95% CI 0.88–0.97, p = 0.003), and reduced risks for all cancers and liver cancer were seen in patients exposed to aspirin (cHR, 0.73; 95% CI, 0.68–0.79; P <.001 for all cancers and cHR, 0.51; 95% CI, 043–0.59; P <.001 for liver cancers).1

In adjusted analyses, there was a reduced risk for all cancers when patients were exposed to aspirin (adjusted hazard ratio [aHR], 0.68; 95% CI, 0.63–0.73) and NSAIDs (aHR, 0.80; 95% CI, 0.75–0.86). Additionally, investigators observed a reduced risk of liver cancer in patients exposed to aspirin (aHR, 0.48; 95% CI, 0.41–0.57) and NSAIDs (aHR, 0.71; 95% CI, 0.62–0.82).1

For mortality, results showed an overall risk reduction for patients exposed to NSAIDs (aHR, 0.68; 95% CI, 0.64–0.72) and a reduced risk for patients exposed to aspirin (aHR, 0.86; 95% CI, 0.82–0.91) after adjusting for comorbidities and severity of the liver disease.1

“Whereas the observed risk reductions should be interpreted with caution, the results may inform future design of explorative clinical trials of aspirin or NSAIDs in selected patients with liver diseases,” investigators concluded.1 “Larger cohort studies could even explore if a dose-response relationship exists with regards to aspirin and NSAIDs and adverse events in patients with liver diseases.”

References

1. Stokkeland K, Söderberg-Löfdal K, Villner P, et al. Aspirin and NSAIDs are Associated With Reduced Cancer and Mortality Risk in Patients With Chronic Liver Diseases—A Swedish Cohort Study. Liver International Communications. https://doi.org/10.1002/lci2.70011

2. American Liver Foundation. How Many People Have Liver Disease? September 11, 2023. Accessed February 10, 2025. https://liverfoundation.org/about-your-liver/facts-about-liver-disease/how-many-people-have-liver-disease/