Massimo Colombo on Why It May Be Time to Recommend Low-Dose Aspirin for Patients At Risk of HCC
Mounting research indicates risk reduction for vulnerable patients at risk, with no increased risk of bleeding
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by Diana Swift
Contributing Writer
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With global rates of hepatocellular carcinoma (HCC) surging, Italian researchers including hepatologist Massimo Colombo, MD, of Humanitas Research Hospital in Rozzano, scanned the recent evidence and, based on their review, made a case for low-dose aspirin as an option for mitigating risk of HCC. Recent research has suggested that aspirin at <160 mg/day could be chemoprotective against HCC development and liver-related mortality in chronic hepatitis B and C patients, without increased risk of bleeding. The Italian review was published recently in Gastroenterology.
Colombo discussed the findings in the following interview.
What was the context in which your group undertook this look at aspirin and HCC?
Colombo:
Despite articulated public health interventions to contain world population exposure to risk factors for HCC, such as hepatitis B and C viruses, as well as increased access to effective hepatitis therapy with unprecedented cure rates, the incidence of this tumor is soaring globally.
In the United States, HCC is the fastest-increasing cause of cancer-related death, with a disproportionate burden in racial/ethnic minorities and people of low socioeconomic status. All in all, this advocates for additional approaches of prevention. Chemoprevention by low-dose aspirin is emerging as an attractive option.
What has the research to date shown about the impact of aspirin on various cancers?
Colombo:
Cohort and population studies have highlighted a reduction in both incidence and mortality for colorectal cancer and in incidence for hepatobiliary cancer, HCC, and, in the context of Lynch syndrome, for endometrial, ovarian, pancreatic, brain, small bowel, gall bladder, ureter, stomach, and kidney cancers. In the Nurses' Health Study, aspirin use after diagnosis of breast cancer was also associated with a reduction in death risk.
Did any of the findings in your current review come as a surprise?
Colombo:
While chemoprevention of HCC by aspirin was expected, following both experimental and epidemiological investigations, what we didn't fully expect was the finding of a reduction in liver-related mortality with low-dose aspirin in such a low-age population of patients 45 years or younger versus the reduction found for the 10-year older average age of Mediterranean patients. Also, quite surprising was the absence of increased bleeding risk.
Could you talk about the probable mechanisms of the protective action of aspirin?
Colombo:
Low-dose aspirin inactivates the immune pathological mechanisms of viral hepatitis that cause inflammation, regeneration, and transformation of liver cells. It suppresses the formation of platelet aggregates and the intrahepatic accumulation of pathogenic CD8+ T cells and other platelet-derived products potentially supporting tumor growth. These include platelet-derived growth factor, vascular endothelial growth factor, insulin-like growth factor, hepatocyte growth factor, and epidermal growth factor, as well as small molecules stimulating hepatocellular proliferation such as serotonin.
What effect would higher or longer doses have?
Colombo:
A dose-response relationship of aspirin in HCC chemoprevention has been highlighted in only a few studies. In the recent New England Journal of Medicine study by Simon et al., there was a duration-risk relationship, and the prevention of metastatic cancer has more often been reported in trials using high-dose aspirin at 300 mg daily.
Have any gastroenterological societies officially embraced low-dose aspirin for risk reduction?
Colombo:
Based on the preliminary 5-year data from the U.K.'s CAPP2 trial, the National Institute for Health and Care Excellence recommended offering aspirin for the prevention of bowel cancer in adults with Lynch syndrome. And the U.S. Preventive Services Task Force recommends initiating low-dose aspirin for the primary prevention of colorectal cancer in adults ages 50 to 59 years who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. The recommendation is conditional for persons ages 60 to 70 years, and aspirin is not recommended for patients older than 70 and younger than 50.
So what's the next step?
Colombo:
We need to do randomized controlled trials.
You can read a summary of the article here, and about the clinical implications of the study here.
No specific funding for this review was disclosed.
Colombo reported ties to Gilead Sciences, MSD, Roche, Bayer, Intercept, Wasserman, Target HCC, Exelixis, and Galapagos.
Co-author Guidotti reported relationships with Genenta Science, Epsilen Bio, and Gilead Sciences. La Vecchia disclosed ties to Teofarma.
Primary Source
Gastroenterology
Source Reference: Guidotti LG, et al "Is it time to recommend low-dose aspirin treatment for the prevention of hepatocellular carcinoma?" Gastroenterology 2020; DOI: 10.1053/j.gastro.2020.09.007.