Heejoon Jang,^1,2* Yun Bin Lee,^1* Hyemi Moon,^3* Jong-Won Chung,⁴ Joon Yeul Nam,¹ Eun Ju Cho,¹ Jeong-Hoon Lee,¹ Su Jong Yu,¹ Yoon Jun Kim,¹ Juneyoung Lee,³ Jung-Hwan Yoon¹

¹Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea ²Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea ³Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea ⁴Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

^*These authors contributed equally to this work.

Address all correspondence and requests for reprints to: Yun Bin Lee, MD, PhD or Juneyoung Lee, PhD

Background & Aims
Studies on differential effect of aspirin therapy on hepatocellular carcinoma (HCC) risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-related death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis.

Approach & 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). The risks of HCC, liver-related 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, the 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% confidence interval [CI], 0.78–0.92). However, among cirrhotics (2,479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85–1.18). The cirrhosis status had a significant effect on the association between aspirin use and HCC risk (P_interaction=0.04). Aspirin use was also associated with lower liver-related 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-related mortality in adults with CHB. The cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.