Life sciences · Journal article

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

Acta Psychologica · September 4, 2026

Strong Evidence Why this matters to you Expert discussion

Well-designed and adequately powered for the question it asks.

AI Summary

This prospective cohort study of 107,363 UK Biobank participants found that adverse childhood experiences show linear dose-response associations with chronic liver disease risk, with those experiencing 4–5 ACEs having twofold higher risk. Mental health, lifestyle, and socioeconomic factors mediate these associations, with overweight/obesity accounting for up to 43.66% of the effect.

What was studied

Prospective cohort study. UK Biobank participants free from chronic liver disease at baseline; ACE assessment conducted in 2016.. Intervention: Adverse childhood experiences (physical neglect, emotional neglect, sexual abuse, emotional abuse, physical abuse); exposure stratified by number (0–5+) and overall intensity.. Compared with: Participants with no or minimal ACE exposure (reference category).. n = 107,363. UK Biobank (United Kingdom).

Key findings

1,888 (1.8%) cases of any CLD identified over mean 13.6-year follow-up Participants with 4–5 ACEs: HR = 2.06 (95% CI: 1.69–2.51) for any CLD and HR = 2.09 (95% CI: 1.66–2.63) for MASLD High overall ACE intensity associated with HR = 1.67 (95% CI: 1.46–1.92) for any CLD and HR = 1.66 (95% CI: 1.41–1.95) for MASLD

Safety

Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.

Who this may help

Clinicians should recognize ACEs as independent risk factors for chronic liver disease and recognize that lifestyle interventions targeting obesity may mitigate a substantial proportion of this risk. Mental health and socioeconomic support may provide additional benefit.

Plain-language summary

Large prospective cohort study with 107,363 participants, hard clinical endpoints (CLD diagnoses from linked medical records), clear dose-response relationships, and rigorous mediation analysis; robust but observational design limits causal inference.

Study design

As stated by the source record.

Methods107,363 UK Biobank participants free from CLD at baseline were followed for a mean of 13.6 years. ACE exposure (physical and emotional neglect, sexual, emotional, and physical abuse) was assessed in 2016. CLD diagnoses, including MASLD, were ascertained through linkage to multiple medical sources. Cox proportional hazards regression was used to estimate hazard ratios; mediation analyses quantified the roles of mental health, lifestyles, and socioeconomic status in the ACE–CLD association. Linear dose-response and non-linearity were tested.

DesignProspective cohort study

PopulationUK Biobank participants free from chronic liver disease at baseline; ACE assessment conducted in 2016.

Sample size107,363

InterventionAdverse childhood experiences (physical neglect, emotional neglect, sexual abuse, emotional abuse, physical abuse); exposure stratified by number (0–5+) and overall intensity.

ComparatorParticipants with no or minimal ACE exposure (reference category).

SettingUK Biobank (United Kingdom)

Reported figures

Quoted from the source exactly as published.

Sample size107363

CLD cases1888

CLD incidence proportion1.8%

Mean follow-up duration13.6 years

HR for any CLD (4–5 ACEs)2.06

95% CI for any CLD (4–5 ACEs)1.69–2.51

HR for MASLD (4–5 ACEs)2.09

95% CI for MASLD (4–5 ACEs)1.66–2.63

Clinical bottom line

Caveats

Observational design; causal inference limited by potential for unmeasured confounding and reverse causality.
ACE exposure assessed retrospectively in 2016; recall bias possible.
UK Biobank cohort may not be fully representative of general population (participation bias).
Absolute risk reduction and baseline CLD risk by ACE category not reported; confidence intervals do not exclude modest effects.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

strong

Prospective cohort with objective CLD ascertainment via medical record linkage.

Directness

strong

Hard clinical endpoints (CLD diagnoses); direct measurement of ACE exposure and mediators.

Consistency

strong

Linear dose-response observed across ACE types and intensity; consistent direction across outcomes.

Risk of bias

moderate

Observational design; potential residual confounding and reverse causality not fully addressed.

Sample adequacy

strong

107,363 participants; 1888 CLD events over 13.6-year mean follow-up provides adequate power.

Source abstract

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 ( P overall < 0.05, P non-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.

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Jinling TangShanshan WuYing LiNana PengShiyu WangJianrong He