Low-Dose Aspirin May Lower Risk of Hepatocellular Carcinoma & Liver-Related Mortality

A nationwide study of patients with chronic viral hepatitis, published in The New England Journal of Medicine, found that low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality compared to no aspirin use, without a significantly higher risk of gastrointestinal bleeding.¹ 

This finding supports the need for randomized clinical trials designed to test the benefits of aspirin for primary prevention of hepatocellular carcinoma. 

“Rates of liver cancer and of mortality from liver disease are rising at an alarming pace in US and European countries,” lead author Tracey Simon, MD, MPH, investigator in the division of gastroenterology and hepatology at Massachusetts General Hospital, said in a press release.² “Despite this, there remain no established treatments to prevent the development of liver cancer, or to reduce the risk of liver-related death.”

Researchers used nationwide Swedish registries to identify 50,275 adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin. They then identified 14,205 patients who were starting to take low-dose aspirin based on their first filled prescriptions for 90 or more consecutive doses of aspirin. Using these data, Cox proportional-hazards regression modeling was used to estimate the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events.

With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was found to be 4.0% among aspirin users and 8.3% among non-users of aspirin (difference, -4.3 percentage points; 95% CI, -5.0 to -3.6; adjusted HR, 0.69; 95% CI, 0.62-0.76). This inverse correlation seemed to be duration-dependent, given that compared with short-term use (3 months to <1 year), the adjusted HRs were 0.90 (95% CI, 0.76-1.06) for 1 to <3 years of use, 0.66 (95% CI, 0.56-0.78) for 3 to <5 years of use, and 0.57 (95% CI, 0.42-0.70) for 5 or more years of use.

Moreover, 10-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted HR, 0.73; 95% CI, 0.67-0.81). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between those who did and did not use aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4). Further, the benefits observed were seen regardless of sex, cause of hepatitis, or underlying compensated cirrhosis, suggesting that the benefits may apply to a broad at-risk population.

“By applying inverse probability of treatment weighting approaches to an unselected population with confirmed viral hepatitis and detailed clinical and medication use data, the current study provides more compelling evidence of the potential hepatoprotective benefits of aspirin,” the authors wrote. “The consistent duration-response associations lend further credence to a potential causal relationship.” 

According to the study, more than 500,000 cases of incident hepatocellular carcinoma are diagnosed each year, primarily related to chronic infection with hepatitis B or hepatitis C virus. Additionally, since the 1990s, the incidences of cirrhosis and hepatocellular carcinoma have dramatically increased in the US and Europe, and mortality from hepatocellular carcinoma is increasing more quickly than that from any other cancer.

References:

1. Simon TG, Duberg A, Aleman S, Chung RT, Chan AT, Ludvigsson JF. Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality. The New England Journal of Medicine. doi:10.1056/NEJMoa1912035.

2. Low-dose aspirin linked to reduced liver cancer risk [news release]. Boston, Massachusetts. Published March 12, 2020. eurekalert.org/pub_releases/2020-03/mgh-lal031220.php. Accessed March 13, 2020.