Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis

Abstract

Background and Aims Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver‐associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis. Approach and Results We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver‐associated mortality, and major bleeding were estimated in a propensity‐score–matched cohort (19,003 pairs), accounting for competing risks. With a median follow‐up of 6.7 years, 10‐year cumulative incidence of HCC was 9.5% in the aspirin‐treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78–0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85–1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (pinteraction, n = 0.04). Aspirin use was also associated with lower liver‐associated mortality (aSHR, 0.80; 95% CI, 0.71–0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99–1.21). Conclusions Aspirin use was associated with reduced risks of HCC and liver‐associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.

Low‐dose aspirin reduces the risk of HBV‐associated HCC even when administered short‐term: Too good to be true?

“…When the analysis was restricted to the 14,689 patients with CHB who had used aspirin for >1 year (and 14,689 untreated), the HR was 0.86 (95% CI 0.78-0.94). [19] A stratified analysis was also provided for patients without cirrhosis versus those with cirrhosis treated or not with aspirin. Among the patients without cirrhosis, 900 cases of HCC were registered in individuals who received aspirin treatment, while there were 1059 HCC cases in untreated individuals, corresponding to an HR of 0.87 (95% CI 0.79-0.95).…”

“…[ 19 ] By defining patients treated with aspirin as those individuals receiving aspirin prescriptions for 90 or more consecutive days, the authors derived a propensity score–matched cohort of 19,003 pairs. [ 19 ] With a median follow‐up of 6.7 years, 2697 patients developed HCC, 1232 in the treated and 1465 in the untreated group. [ 19 ] The 10‐year cumulative incidence of HCC was 9.5% in the treated versus 11.3% in the untreated group, corresponding to an adjusted HR of 0.85 (95% CI, 0.78–0.92).…”

“…The HR was apparently greater in patients with cirrhosis (1.15) than in those without cirrhosis (1.05), but, again, the heterogeneity was not significant. [ 19 ]…”

“…[ 19 ] The 10‐year cumulative incidence of HCC was 9.5% in the treated versus 11.3% in the untreated group, corresponding to an adjusted HR of 0.85 (95% CI, 0.78–0.92). [ 19 ] Aspirin use for 90 or more consecutive days was therefore inversely related to HCC, but there was no evidence of a duration–risk relationship. When the analysis was restricted to the 14,689 patients with CHB who had used aspirin for >1 year (and 14,689 untreated), the HR was 0.86 (95% CI 0.78–0.94).…”

“…Among the patients without cirrhosis, 900 cases of HCC were registered in individuals who received aspirin treatment, while there were 1059 HCC cases in untreated individuals, corresponding to an HR of 0.87 (95% CI 0.79–0.95). [ 19 ] By contrast, there was no association with aspirin use and reduced HCC risk among patients with cirrhosis: 323 and 333 HCCs were observed in aspirin‐treated versus aspirin‐untreated individuals with cirrhosis, corresponding to an adjusted HR of 1.00 (95% CI 0.85–1.15). [ 19 ] The latter finding may depend on cirrhosis‐linked thrombocytopenia, which could have weakened the capacity of aspirin to inhibit platelet function.…”