Low-dose Aspirin and Mortality in chronic Viral Hepatitis

In liver clinic, you are seeing a 47-year-old patient with chronic hepatitis C infection and are accompanied by a medical student rotating on the hepatology service. The patient has been doing well, and his last ultrasound scan showed no evidence of cirrhosis. As you close out the visit, the medical student asks whether you will prescribe aspirin, reminding you of a study discussed in the recent journal club. The study found that low-dose aspirin reduced the risk of cancer and liver-related death in patients with chronic viral hepatitis. You discuss the results of the trial and implications for potential aspirin use with the patient and medical student.

Aspirin’s anti-inflammatory effects, particularly via effects on the cyclooxygenase-2 (COX-2) enzyme, may be beneficial in the treatment of chronic liver disease. In an earlier prospective study, researchers demonstrated that daily aspirin use slowed the progression to fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Now, the same authors reported the efficacy of aspirin in a nationwide study of patients in Sweden with chronic hepatitis B or C infection. They found that during the 10-year study, daily use of low-dose aspirin reduced the rate of progression to hepatocellular carcinoma and liver-related mortality. Aspirin delivered this benefit without increasing the risk of gastrointestinal bleeding. These results strengthen the case for aspirin use in patients with NAFLD.

The following NEJM Journal Watch summary explains the study in more detail.

Atif Zaman, MD, MPH reviewing Simon TG et al. N Engl J Med 2020 Mar 12

In several experimental and clinical studies, aspirin use is associated with reduced progression of liver disease and hepatocellular carcinoma (HCC) risk. Possible mechanisms include modulation of bioactive lipids, which is in line with recent evidence that statins might reduce HCC risk (NEJM JW Gastroenterol Oct 2019 and Ann Intern Med 2019;171:318).

To investigate this link further using detailed epidemiologic data, researchers conducted a propensity score–matched cohort study in Swedish residents with chronic hepatitis B or C infection diagnosed between 2005 and 2015. Data on use of low-dose aspirin (≤160 mg daily), liver-related mortality, incident HCC, and gastrointestinal bleeding came from national health registries and were prospectively collected. 

The study cohort included about 14,000 aspirin users (14% with cirrhosis) and about 36,000 nonusers (14% with cirrhosis). During a median follow-up of 7.9 years, the estimated 10-year cumulative incidence of HCC was significantly lower in aspirin users than in nonusers (4% vs. 8%; adjusted hazard ratio, 0.69), and this inverse risk relationship was duration-dependent based on years of aspirin use. Ten-year liver-related mortality was also significantly lower in aspirin users versus nonusers (11% vs. 18%; adjusted HR, 0.73). The gastrointestinal bleeding risk did not differ between groups (7%–8%).

Comment: These are the same national registries from which researchers initially demonstrated that statin users had reduced risk for HCC. Based on the current analysis, like statin use, low-dose aspirin use should not be discouraged in patients with chronic viral hepatitis, even in those with cirrhosis. If these results are replicated in future studies, including randomized, controlled trials, then use of both statins and low-dose aspirin should be encouraged in patients with chronic HBV or HCV infection.

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Krista is a 2019-2020 editorial fellow at the New England Journal of Medicine. She is from Nassau, Bahamas where she is training in general surgery at the University of the West Indies.