Low-Dose Aspirin Could Reduce Risk of Liver Cancer

Jonas Ludvigsson, MD, PhD

While low-dose aspirin has long been a staple in treatment for patients at risk of cardiovascular disease, new research from an international team of investigators has found a potential link between the use of aspirin and a reduction in the most common type of liver cancer.

Results of the study, which analyzed data from more than 50,000 patients, found those at high risk of developing hepatocellular carcinoma who were receiving low-dose aspirin saw reductions in cancer and liver-related deaths—with the observed benefit becoming greater the longer a person was taking low-dose aspirin.

"This is the first large-scale, nationwide study to demonstrate that the use of aspirin is associated with a significantly reduced long-term risk of liver cancer and liver-related mortality," said lead investigator Jonas Ludvigsson, MD, PhD, of the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet, in a statement.

With a growing amount of data suggesting that aspirin may prevent progression of liver disease and hepatocarcinogenesis, Ludvigsson and colleagues from Massachusetts General Hospital sought to examine whether the use of low-dose aspirin—defined as 160 mg or less—was associated with a decrease in incident hepatocellular carcinoma, liver-related mortality, or gastrointestinal bleeding. To do so, they pulled information from the nationwide Swedish Register for Surveillance of Communicable Diseases on patients with acute and chronic hepatitis B or hepatitis C monoinfection.

The patient population for the current analysis included 50,275 patients, including 13,276 with hepatitis B and 36,999 with hepatitis C. Of the 50,275, investigators identified 14,205 aspirin users and 36,070 who met their criteria for nonusers. OF the 14,205 aspirin users, 56% had coronary artery disease, 87% had at least 1 cardiovascular risk factor, and 84% filled predictions for 290 or more consecutive cumulative defined daily doses after initial prescription.

Through the use of propensity matching and applied inverse probability, investigators were able to balance baseline characteristics between groups. Use of Cox proportional-hazards regression modeling was used to estimate the risk of hepatocellular carcinoma and liver-related mortality, which were the primary outcomes, over a median of 7.9 years of follow-up. In total, 1612 incident cases of hepatocellular carcinoma and 5017 liver-related deaths were observed during the follow-up.

Results of the analysis indicate the 10-year cumulative incidence of hepatocellular carcinoma was 4.0% among low-dose aspirin users and 8.3% among nonusers(-4.3 percentage point difference; P<.001). This correlated to a 31% lower risk of hepatocellular carcinoma than nonusers after multivariable adjustment (aHR 0.69; 95% CI, 0.62-0.76).

In regard to liver-related mortality, the 10-year rate was 11.0% among low-dose aspirin users and 17.9% in the nonuser group (-6.9 percentage point difference;P<.001). Results of the analysis correlated to a 27% reduction in risk of liver-related mortality after multivariable adjustment (aHR 0.73; 95% CI, 0.67 to 0.81).

Data from the analysis also indicated the benefits of taking low-dose aspirin appeared to increase over time. When comparing to short-term use, which was defined as 3 months to 1 year, use for 1-3 years decreased risk of hepatocellular carcinoma by 10%, 3-5 years decreased the risk by 34%, and use for 5 years or more lowered risk by 43%.

"Rates of liver cancer and of mortality from liver disease are rising at an alarming pace in U.S. and European countries. Despite this, there remain no established treatments to prevent the development of liver cancer, or to reduce the risk of liver-related death," said Tracey Simon, MD, MPH, an investigator in the Division of Gastroenterology and Hepatology at Massachusetts General Hospital, in the aforementioned statement.

This study, “Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality,” was published in the New England Journal of Medicine.