March 11, 2020
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Aspirin may reduce risk for hepatocellular carcinoma, liver-related mortality in chronic viral hepatitis

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Tracey Simon, MD, MPH
Tracey Simon

Low-dose aspirin use appeared associated with significantly lower risk for hepatocellular carcinoma and lower liver-related mortality among patients with chronic viral hepatitis, according to results of a retrospective study published in The New England Journal of Medicine.

Moreover, low-dose aspirin did not significantly increase risk for gastrointestinal bleeding in this patient population.

“There is growing evidence that aspirin may offer unique benefits for patients with liver disease,” Tracey Simon, MD, MPH, hepatologist in the division of gastroenterology and instructor of medicine at Harvard Medical School, told Healio. “Several recent studies from our group and others have linked aspirin use to a reduced risk for liver fibrosis progression and to a lower risk for developing liver cancer. In animal models, there is also compelling evidence that aspirin may prevent the development of liver cancer by acting on anti-inflammatory pathways within the liver.”

Experimental and clinical data have suggested that aspirin may prevent liver disease progression and hepatocarcinogenesis by preventing platelet degranulation, modulating bioactive lipids and inhibiting the proinflammatory cyclooxygenase-2 (COX-2) enzyme, among other potential mechanisms.

Low-dose aspirin use appeared associated with significantly lower risk for HCC and lower liver-related mortality among patients with chronic viral hepatitis.

However, limited data exist regarding the long-term effects of low-dose aspirin, defined as less than 160 mg, on incidence of hepatocellular carcinoma, liver-related mortality and gastrointestinal bleeding among patients with chronic hepatitis B or hepatitis C, according to the researchers.

“Our study adds to the body of evidence because it is the first analysis in a nationwide, unselected Western population with confirmed viral hepatitis,” Simon told Healio. “It is important because it confirms prior evidence and also demonstrates significant benefits with longer duration of aspirin use.”

Simon and colleagues used nationwide registries to identify all adults in Sweden diagnosed with hepatitis B or hepatitis C between 2005 and 2015 who did not have a prior history of aspirin use (n = 50,275). They identified individuals who started to take low-dose aspirin (n = 14,205) by their first filled prescription for 90 or more consecutive doses of aspirin.

Researchers created a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between the aspirin user and nonuser (n = 36,070) groups. Cox proportional hazards regression modeling enabled investigators to estimate risk for hepatocellular carcinoma and liver-related mortality while accounting for competing events.

Median follow-up was 7.9 years (range, 2-9.8).

Results showed an estimated 10-year cumulative incidence of hepatocellular carcinoma of 4% among aspirin users and 8.3% among nonusers, for a difference of 4.3 percentage points (95% CI, 5 to 3.6). Multivariable-adjusted analysis showed aspirin users had a 31% lower risk for hepatocellular carcinoma vs. nonusers (adjusted HR [aHR] = 0.69; 95% CI, 0.62-0.76).

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The inverse association appeared to be dependent upon duration of aspirin use.

When compared with short-term aspirin use, defined as 3 months to less than 1 year, researchers observed aHRs of 0.9 (95% CI, 0.76-1.06) for aspirin use of 1 year to less than 3 years, 0.66 (95% CI, 0.56-0.78) for 3 years to less than 5 years of use, and 0.57 (95% CI, 0.42-0.7) for 5 or more years of use.

Results also showed a 10-year liver mortality rate of 11% among aspirin users and 17.9% among nonusers (aHR = 0.73; 95% CI, 0.67-0.81).

However, 10-year risk for gastrointestinal bleeding appeared similar between aspirin users and nonusers (7.8% vs. 6.9%; difference, 0.9 percentage points; 95% CI, 0.6 to 2.4).

A lack of information on smoking, hepatitis B DNA levels, hepatitis C eradication, specific fibrosis stages, hepatocellular carcinoma screening, aflatoxin exposure, coffee consumption and aspirin adherence served as a limitation to this study.

“Our findings are very exciting and will hopefully pave the way for future randomized clinical trials of aspirin use among at-risk patients with liver disease,” Simon said. “However, before aspirin can be recommended to patients with liver disease, we must first determine its safety and efficacy in different types and severities of liver disease. We are looking forward to conducting randomized clinical trials to test the safety and efficacy aspirin use in patients with chronic liver disease.” – by John DeRosier

For more information:

Tracey Simon, MD, MPH, can be reached at Gastroenterology Associates, 55 Fruit St., Boston, MA 02114-2696; email: tgsimon@mgh.harvard.edu.

Disclosures: Simon reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.