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SAN FRANCISCO -- Taking aspirin a couple of times per week appeared to significantly lower the risk of developing hepatocellular carcinoma (HCC), researchers said here.

In two large cohorts of health professionals, regular aspirin use was associated with about a 50% reduction in liver cancer incidence, with greater benefits accruing to those who took it more often or for a longer duration, reported Tracey Simon, MD, of Massachusetts General Hospital in Boston the annual annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

A growing body of evidence indicates that aspirin may help reduce cancer risk. The recommends that people ages ≥50 with elevated cardiovascular risk consider low-dose aspirin to prevent cardiovascular disease, noting that it has also been shown to reduce the risk of colorectal cancer. But regular aspirin use also caries risks, including gastrointestinal bleeding and hemorrhagic stroke.

Simon and colleagues evaluated the influence of aspirin use, dose, and duration on the risk of developing HCC in two prospective cohort studies. The enrolled 121,706 women in 1976 and the enrolled 51,529 men in 1986. The pooled analysis included a total of 133,371 individuals who answered baseline health questions at the midpoint of follow-up in 1996. (The study was also published recently in JAMA Oncology.)

Regular aspirin use was defined as taking at least 325 mg at least twice weekly. Among the 58,855 people who regularly used aspirin, 62% were women and the mean age was 64. Among the 74,516 aspirin non-users, 68% were women and the mean age was 62. In both groups, almost all participants were white and just over 10% were current smokers.

As expected, regular aspirin users were significantly more likely than non-users to have hypertension (37% versus 26%) and to be using statins (12% versus 6%). In addition, about 20% also reported using non-aspirin NSAIDs.

A total of 108 new cases of HCC were diagnosed during follow-up: 37 cases during 1,738,231 person-years among regular aspirin users, and 71 cases during 2,493,957 person-years among non-users.

The risk of incident HCC was 49% lower among aspirin users compared with non-users in a multivariate analysis that included age, sex, race, body mass index, alcohol use, smoking, physical activity, diabetes, hypertension, dyslipidemia, and regular use of multivitamins, diabetic medications, and statins. Similar risk reduction was observed for women (51%) and men (46%), Simon said.

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

Among current aspirin users, there was a significant trend of greater risk reduction with longer use. Regular use for up to 5 years was associated with a 13% reduction, 5 to 10 years with a 41% reduction, and ≥10 years with a 49% reduction in risk. Among those who previously used aspirin, HCC risk returned the level of non-users 8 years after stopping.

Taken together, a significant benefit was apparent after ≥5 years of use at an average dose of at least 1.5 tablets per week, Simon said. In contrast, there was no apparent HCC risk reduction associated with use of acetaminophen or non-aspirin nonsteroidal anti-inflammatory drugs (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."

Asked to speculate about possible biological mechanisms underlying the link between aspirin use and HCC risk, Simon suggested a few possibilities.

"One of the most obvious low-hanging fruits would be that, by inhibiting platelet degranulation, it reduces the release of pro-inflammatory cytokines and chemokines, and that might either delay the progression of fibrosis -- and thus secondarily prevent the incidence of HCC -- or the anti-inflammatory effect might itself lead to the reduction in HCC risk," Simon told MedPage Today. "There's also some data showing that aspirin reduces intrahepatic lipid accumulation, so in the setting of patients with NASH [non-alcoholic steatohepatitis], that might be the mechanism."

AASLD session moderator W. Ray Kim, MD, of Stanford University Medical Center in California, emphasized that it's important to understand the effect of aspirin earlier in the process that leads to the development of HCC.

"Most of the time HCC is a two-step process. You first need to get to chronic liver disease, which is present in 90%-plus of [HCC] patients, and then you develop HCC," he told MedPage Today. "When I hear data on a population-wide basis that something increases the risk of HCC, I ask, does it increase the risk of chronic liver disease as a first step? It's important to try to stratify the population -- for example, in patients with chronic liver disease, does taking aspirin reduce HCC? That would be a smaller study and I look forward to seeing that data."

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