TP53 and hepatocellular carcinoma: In total, 75.2% of patients with CCA were identified to have signature D of aristolochic acid (AA) exposure, which has been reported in iCCA and HCC in Chinese cohorts.16,17 We observed that patients with iCCA have more AA exposure than patients with eCCA (Figure S1H), and patients with AA exposure showed significantly higher TP53 mutations and immune scores (Figure 1F; Figure S1I), Consistently, AA exposure has been reported to induce TP53 mutation.17 These findings implicated that AA exposure had a critical role in CCA development.