Chronic
inflammation plays a pivotal role in the pathogenesis of
hepatocellular carcinoma (HCC) and
intrahepatic cholangiocarcinoma (ICC), the two most common types of
liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (
NSAIDs), including
aspirin and
ibuprofen, may potentially protect against
liver cancer. However, no observational study has examined the association between
aspirin duration and dose or other over-the-counter non-
aspirin NSAIDs, such as
ibuprofen, and
liver cancer incidence. Furthermore, the association between
NSAID use and risk of ICC is unclear. As part of the
Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current
aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-
aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between
aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage.
Ibuprofen use was not associated with HCC risk.
Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between
aspirin use and
liver cancer in our study, together with previous data, suggests the merit of future intervention studies of
aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.