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.
Glossary
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
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.