Associations of ClivD score with Dementia, Cardiovascular Disease, Cancer, and Mortality in the General Population using data from UK Biobank: a prospective cohort study

Background The ClivD score, a non-invasive marker for liver disease risk, shows strong predictive value for advanced liver disease. Given emerging links between chronic liver diseases and systemic conditions, this study examines ClivD's association with risks of cardiovascular disease, dementia, cancer, and all-cause mortality. Methods This prospective cohort study included eligible adult participants from the UK Biobank who had calculable ClivD scores between 2006 and 2010. Data were analyzed using Cox proportional hazards models, Kaplan–Meier (KM) survival curves, and restricted cubic spline (RCS) functions. Results This prospective cohort study included 84,469 UK Biobank participants with calculable ClivD scores (2006–2010) and a mean 9.77-year follow-up. During follow-up, 4,664 participants died, and 966 developed dementia; 8,347 experienced CVD events, and 15,152 were diagnosed with cancer. Compared to the lowest ClivD quartile (Q1), the highest quartile (Q4) was associated with significantly elevated risks of dementia (HR = 4.30 for ClivD _lab ; 3.31 for ClivD _nonlab ), CVD (HR = 2.72 for ClivD _lab ; 2.36 for ClivD _nonlab ), cancer (HR = 2.05 for ClivD _lab ; 1.86 for ClivD _nonlab ), and mortality (HR = 3.91 for ClivD _lab ; 3.28 for ClivD _nonlab ), all p < 0.001. Associations with secondary outcomes (e.g., Alzheimer’s disease, vascular dementia, stroke, coronary heart disease, heart failure) were also significant. KM curves showed higher event incidence in high-risk groups; RCS analysis revealed mostly nonlinear associations, except for stroke in relation to ClivD _nonlab (linear trend). Subgroup and sensitivity analyses supported the robustness of findings. Conclusions Higher ClivD scores are strongly associated with increased risks of dementia, CVD, cancer, and mortality in the general population. These findings support integrating ClivD into chronic disease risk stratification frameworks to enable earlier detection and liver-informed preventive strategies.