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.

Background/Aims: Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients.Methods: Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias.Results: Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04).Conclusions: After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.