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Association of aspirin with hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis.
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Aspirin Prevents HCC in People With HBV, But Not if They Have Cirrhosis
AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
In a nationwide Korean analysis of people with chronic HBV, those prescribed aspirin ran a lower risk of hepatocellular carcinoma (HCC) and liver mortality [1]. But aspirin did not protect people who already had cirrhosis in this matched comparison of thousands of pairs with or without an aspirin prescription.
Studies exploring the HCC-preventing potential of aspirin in people with viral hepatitis are huge, multilayered, and sometimes contradictory. A nationwide 8-year study of people in Sweden with chronic HBV or HCV linked low-dose aspirin to a significantly lower risk of HCC or liver-related death, with no higher risk of gastrointestinal bleeding [2]. A nationwide Korean case-control study initially found a lower HCC risk with aspirin or statins in HBV patients without cirrhosis [3]. But aspirin's protective effect disappeared in further analyses, in which statin use appeared to confound the impact of aspirin.
Like the Korean aspirin-statin analysis [3], the Korean aspirin study drew data from people covered in the Korean National Health Insurance Service database, in this case from January 2002 through December 2017 [1]. The researchers included people with chronic HBV infection and excluded those with HCV, HIV, no health exam data, or a cancer diagnosis or major bleeding before the index date. They defined treated people as those prescribed aspirin for at least 90 consecutive days and untreated people as those never prescribed any antiplatelet. The index date was 180 days after the first aspirin prescription for the treated group and the first health exam date for the untreated group.
The researchers matched each aspirin-treated person with one untreated person by age, sex, total cholesterol, serum glucose or history of diabetes, body mass index, blood pressure or history of hypertension, AST, ALT, GTP, liver cirrhosis, decompensated cirrhosis, antiviral agent, metformin, statin, and anticoagulant.
That exercise yielded 19,003 aspirin-treated people and 19,003 people never prescribed an antiplatelet drug. There were 16,507 pairs without cirrhosis and 2479 pairs with cirrhosis. Because of matching, the overall treated and untreated groups were similar in age (55 and 54), proportions of men (75.4% and 75.8%), and body mass index (25.1 and 25.1 kg/m2). The treated group had a minimally but significantly lower proportion with cirrhosis (13.2% vs 13.3%, P = 0.004) and a small but significantly lower proportion who got antiviral therapy (13.5% vs 13.8%, P = 0.009).
Through a median 6.7 years of follow-up, HCC developed in 2697 people. Those prescribed aspirin had a 15% lower risk of HCC (adjusted hazard ratio [aHR] 0.85, 95% confidence interval [CI] 0.78 to 0.92, P < 0.001). The lower risk with prophylactic aspirin held true in people without cirrhosis (aHR 0.87, 95% CI 0.79 to 0.95, P < 0.001). But limiting the analysis to people with cirrhosis completely wiped out aspirin's protective effect against HCC (aHR 1.00, 95% CI 0.85 to 1.18, P = 0.51).
In the overall population, aspirin prophylaxis cut the risk of liver-related death 20% (aHR 0.80, 95% CI 0.71 to 0.90, P < 0.001). Again that protective effect held firm in people without cirrhosis (aHR 0.84, 95% CI 0.73 to 0.97, P = 0.001) but not in those with cirrhosis (aHR 0.91, 95% CI 0.72 to 1.1, P = 0.10).
In the whole study group, an aspirin prescription inflated the risk of major bleeding almost 10%, but that association lacked statistical significance (aHR 1.09, 95% CI 0.99 to 1.21, P = 0.15). Aspirin did significantly swell the risk of major bleeding in people without cirrhosis (aHR 1.15, 95% CI 1.03 to 1.28, P = 0.03) but not in those with cirrhosis (aHR 1.05, 95% CI 0.84 to 1.31, P = 0.64).
The researchers concluded that aspirin is associated with a lower risk of HCC in people with chronic HBV infection, but not if they already have cirrhosis. Having cirrhosis also erases the lower risk of liver mortality seen in people taking aspirin.
References
1. Jang H, Lee YB, Moon H, et al. Association of aspirin with hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 159.
2. Simon TG, Duberg AS, Aleman S, Chung RT, Chan AT, Ludvigsson JF. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020;382:1018-1028. doi: 10.1056/NEJMoa1912035.
3. Choi WM, Kim HJ, Ko MJ, et al. Association of aspirin and statin use with hepatocellular carcinoma risk in treatment-naive non-cirrhotic patients with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 137. (Reported separately by NATAP.)
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