Association Between Depressive Symptoms and Risk of New-Onset Chronic Liver Disease Among Middle-Aged and Elderly Chinese Adults: A Prospective Cohort Study Based on the China Health and Retirement Longitudinal Study

Abstract

Background: Chronic liver disease (CLD) imposes a heavy global burden, particularly among middle-aged and elderly adults. Prospective evidence on whether depressive symptoms independently predict new-onset CLD remains scarce. Methods: This prospective cohort study used CHARLS (2011–2020) data and enrolled 9549 participants without baseline CLD. Depressive symptoms were assessed using the CES-D-10 and categorized into four severity levels. Multivariable Cox regression, Kaplan–Meier analysis, and ROC curves were used. Subgroup analyses were conducted across demographic and behavioral strata to assess consistency. Results: During a mean follow-up of 8.77 years, 746 (7.8%) participants developed new-onset CLD. Higher baseline depression severity was associated with increased CLD risk. In the fully adjusted model, compared with the non-depressed group, the HR for mild depression was 1.34 (95% CI: 1.12–1.59, p = 0.001), for moderate depression 1.65 (95% CI: 1.34–2.04, p < 0.001), and for severe depression 2.16 (95% CI: 1.26–3.72, p = 0.005). Cumulative incidence increased with depression severity, with group differences widening over time (log-rank p < 0.0001). Subgroup analyses showed consistent associations across different demographic and behavioral strata. Conclusions: Across the total population, the analyses consistently demonstrate an independent, graded association between baseline depressive symptom severity and incident CLD that persists after multivariable adjustment. The stratified analyses further reveal that this association is primarily driven by female participants and middle-aged adults (45–60 years), highlighting these subgroups as priority populations for depression-informed CLD prevention and screening strategies.