Longitudinal frailty trajectories and risk of incident chronic liver disease among middle-aged and older Chinese adults: the mediating role of depressive symptoms

Background Chronic liver disease imposes a substantial global health burden, a challenge further compounded by population aging. Prior studies have predominantly relied on frailty index assessments at a single baseline time point, the study is the first to apply group‑based trajectory modeling to construct longitudinal frailty index trajectories, with the aim of elucidating their independent association with incident CLD among middle‑aged and older Chinese adults and further exploring the potential mediating role of depressive symptoms. Methods To examine the association between frailty and incident chronic liver disease (CLD) and the mediating role of depressive symptoms, we enrolled 7,363 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS) and performed Cox proportional hazards regression and mediation analyses. Results Over 5 years, 385 participants developed chronic liver disease. After adjustment for confounders, individuals in the frailty‑worsening trajectory group had a 48% increased risk of incident chronic liver disease (CLD) (HR = 1.48, 95% CI: 1.16–1.90). Depressive symptoms mediated 25.6% of the total effect, which was statistically significant yet relatively modest in magnitude Conclusion Among middle‑aged and older Chinese adults, a frailty‑worsening trajectory was significantly associated with the risk of incident chronic liver disease, and depressive symptoms partially mediated this association. This finding suggests that regular comprehensive assessment of both physical function and mental health in older adults may represent an important strategy for CLD prevention.