Aspirin use associated with lower risk of liver cancer

Taking aspirin about twice a week for five years or more may reduce the risk of developing hepatocellular carcinoma (HCC) by about half, according to research presented this week at the AASLD Liver Meeting in San Francisco.

Over years or decades, chronic hepatitis B or C virus (HBV or HCV) infection, heavy alcohol use, fatty liver disease or other causes of liver damage can lead to the development of cirrhosis and HCC, the most common type of cancer that originates in the liver. HCC is often diagnosed at a late stage, is difficult to treat and is a leading cause of cancer deaths worldwide.

A growing body of research suggests that aspirin may help reduce cancer risk. Daily low-dose aspirin, recommended to prevent cardiovascular disease in those at high risk, has also been shown to lower the risk of colorectal cancer. It also appears to reduce the likelihood of developing other types of cancer. But regular aspirin use also carries risks, including gastrointestinal bleeding.

Dr Tracey Simon of Massachusetts General Hospital in Boston and colleagues evaluated the effect of aspirin use on the risk of developing liver cancer in two large cohort studies. The Nurses Health Study enrolled 121,706 women in 1976 and the Health Professionals Follow-Up Study enrolled 51,529 men in 1986. The pooled analysis included 133,371 individuals who answered baseline health questions.

Regular aspirin use was defined as taking at least 325mg of aspirin at least twice a week. A total of 58,855 individuals said they regularly used aspirin, while 74,516 did not.

In both groups, about two thirds were women, almost all were white, the mean age was in the early sixties and just over 10% were current smokers. Regular aspirin users were more likely than non-users to have high blood pressure (37% vs 26%, respectively) and to use statins (12% vs 6%). About 20% also reported using non-aspirin non-steroidal anti-inflammatory medications (NSAIDs).

During follow-up, 37 cases new cases of HCC were diagnosed among regular aspirin users (1,738,231 person-years of follow-up) and 71 cases were detected among non-users (2,493,957 person-years).

The risk of developing HCC was reduced by 49% among aspirin users compared with non-users in a multivariate analysis that included demographics, body mass index, alcohol use, smoking, physical activity and cardiovascular risk factors. A similar degree of risk reduction was observed for both women and men (51% and 46%, respectively).

Looking at cumulative doses over time, a significant reduction in HCC risk was seen among people who used at least 1.5 aspirin tablets (487.5mg) per week, or the equivalent of about 70mg per day.

Looking at duration of use, among current aspirin users there was greater HCC risk reduction with longer use. Regular use for up to five years was associated with a 13% reduction, five to 10 years with a 41% reduction and 10 or more years with a 49% reduction in risk. Among those who previously used aspirin, HCC risk returned to the level of non-users eight years after stopping.

Taken together, a significant benefit of aspirin was apparent after five or more years of use at an average dose of at least 1.5 tablets per week, according to Simon. In contrast, there was no apparent HCC risk reduction associated with use of acetaminophen or non-aspirin NSAIDs.

"Our findings suggest that the potential chemopreventive effects of aspirin may extend beyond colorectal cancer," the researchers concluded. "Understanding the mechanistic basis for these associations may help inform the development of novel anti-inflammatory HCC primary prevention strategies."

Regarding the biological mechanisms underlying the effect, Simon suggested that aspirin's anti-inflammatory effect might either delay progression of fibrosis or directly reduce HCC risk. She said there is also data showing that aspirin reduces lipid accumulation in the liver, which could play a role in HCC prevention among people with fatty liver disease.