Low-dose aspirin was associated with lower rates of hepatocellular carcinoma (HCC) and 10-year liver-related mortality among patients with hepatitis B (HBV) or hepatitis C virus (HCV), according to results from a Swedish registry study.1

Chronic HBV or HCV infection are associated with a high risk of developing HCC. Based on experimental and clinical data, it has been hypothesized that aspirin may prevent the progression of liver disease or carcinogenesis due to its mechanisms of action, such as inhibition of the proinflammatory enzyme COX-2, modulation of bioactive lipids, and inhibition of platelet degranulation.

The purpose of this study was to determine the relationship between low-dose aspirin use and HCC, liver-related mortality, and bleeding risks among patients with chronic HBV or HCV infection.

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The study included 50,275 adults with chronic HBV or HCV infection between 2005 and 2015 who did not have a prior history of aspirin use from the nationwide Swedish Registry for Surveillance of Communicable Diseases. Of these patients, 14,205 were identified as beginning low-dose aspirin based on their first filled prescription of at least 90 consecutive doses of aspirin, which had to occur 180 days after their diagnosis of HBV or HCV infection. Among these patients, 84% filled subsequent aspirin prescriptions. Non–aspirin users were considered those who did not fill an aspirin prescription. In Sweden, low-dose aspirin is available by prescription only.

Patients with HIV, prior HCC, or prior filled prescriptions of aspirin or other antiplatelet agents before the 180-day period were excluded from the analysis.

Aspirin users were significantly less likely to develop HCC, with a 10-year cumulative incidence of 4.0% (95% CI, 3.6-4.4) compared with 8.3% (95% CI, 8.1-8.5) among non-aspirin users. After multivariable adjustment, this translated to a 31% decrease in risk of HCC (subhazard ratio [SR], 0.69; 95% CI, 0.62-0.76).

Longer duration of use was associated with lower HCC risk. Low-dose aspirin use of 1 to 3 years was not protective, whereas aspirin use of 3 to 5 years decreased the risk of HCC by 34% (adjusted SR, 0.66; 95% CI, 0.56-0.78) and aspirin use for 5 years or longer decreased the risk by 43% (adjusted SR, 0.57; 95% CI, 0.42-0.70). The protective effect diminished after aspirin discontinuation. 

Low-dose aspirin use was also associated with lower 10-year liver-related mortality. The rate of liver-related mortality was 11.0% (95% CI, 10.8-11.2) among aspirin users compared with 17.9% (95% CI, 17.8-18.0) among non-aspirin users.

The incidence of 10-year cumulative gastrointestinal bleeding was similar between aspirin users and nonusers at 7.8% and 6.9%, respectively.

“Our findings support the need for randomized clinical trials designed to test the benefits of aspirin for primary prevention of HCC,” the authors concluded.


Simon TG, Duberg A-S, Aleman S, et al. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020;382:1018-1028.