Adverse childhood experiences and chronic liver diseases: Dose-response, type-specific associations, and mediation analyses.

BACKGROUND: Adverse childhood experiences (ACEs) are linked to long-term health risks, yet their association with chronic liver diseases (CLDs) and mediating roles of mental health, lifestyles, and socioeconomic status remain undefined. We aimed to investigate these associations. METHODS: This prospective cohort study included 107,363 UK Biobank participants free from CLDs at baseline. CLD diagnoses were ascertained through linkage to multiple sources. The primary outcomes were any CLD and metabolic dysfunction-associated steatotic liver disease (MASLD). Physical and emotional neglect, sexual, emotional, and physical abuse were assessed in 2016. Cox regression and mediation analyses were used. RESULTS: We identified 1888 (1.8%) cases of any CLD over a mean 13.6-year follow-up. Physical neglect and sexual/physical abuse were associated with higher risks of any CLD and MASLD. Linear dose-response relationships were observed between the number and overall intensity of ACE and any CLD and MASLD (Poverall < 0.05, Pnon-linearity > 0.05). Participants with 4-5 ACEs exhibited twofold or greater risks of any CLD (HR = 2.06; 95% CI: 1.69-2.51) and MASLD (HR = 2.09; 95% CI: 1.66-2.63). High overall ACE intensity was associated with more than 60% higher risks of any CLD (HR = 1.67; 95% CI: 1.46-1.92) and MASLD (HR = 1.66; 95% CI: 1.41-1.95). Mental health, lifestyles, and socioeconomic status were significant mediators, among which overweight/obesity mediates the largest proportion (up to 43.66%). CONCLUSIONS: ACEs are independent risk factors for CLDs, mediated by mental disorders, lifestyles, and socioeconomic status. Reducing ACE exposure and addressing overweight/ obesity may be effective strategies to mitigate ACE-related CLD risks.