Associations of CLivD score with dementia, cardiovascular disease, cancer, and mortality in the general population from the UK biobank

Abstract

Abstract Background The Chronic Liver Disease (CLivD) score is a non-invasive marker of advanced liver disease risk. We evaluated its associations with dementia, cardiovascular disease (CVD), cancer, and all-cause mortality. Methods This prospective cohort study included UK Biobank participants with calculable CLivD scores at baseline (2006–2010). Two previously validated versions of the score were calculated: a laboratory-based CLivD (CLivD lab ), incorporating age, sex, waist-hip ratio, alcohol consumption, diabetes, smoking, and gamma-glutamyltransferase (GGT), and a non-laboratory CLivD (CLivD nonlab ), based on the same predictors without GGT. Data were analyzed using Cox proportional hazards models, Kaplan–Meier survival curves, and restricted cubic spline functions. Additional models adjusted for centered age and sex. Results This prospective cohort study included 88,449 UK Biobank participants with calculable CLivD scores (2006–2010) and a mean 9.76-year follow-up. During follow-up, 1,052 (1.19%) developed dementia, 8,814 (9.97%) experienced CVD, 15,882 (17.96%) were diagnosed with cancer, and 4,944 (5.59%) participants died. Compared to the lowest CLivD quartile (Q1), the highest quartile (Q4) was associated with significantly elevated risks of dementia (CLivD lab : HR = 5.57, 95% CI [4.37–7.11]; CLivD nonlab : HR = 4.39, 95% CI [3.51–5.50] ), CVD (CLivD lab : HR = 4.23, 95% CI [3.93–4.55]; CLivD nonlab : HR = 3.59, 95% CI [3.34–3.85] ), cancer (CLivD lab : HR = 2.27, 95% CI [2.17–2.38]; CLivD nonlab : HR = 2.11, 95% CI [2.01–2.21] ), and mortality (CLivD lab : HR = 4.77, 95% CI [4.31–5.28]; CLivD nonlab : HR = 4.14, 95% CI [3.76–4.56] ), all p values < 0.001. Associations were attenuated after additional adjustment for centered age and sex, but the highest CLivD lab quartile remained associated with all four outcomes. Higher CLivD scores were also associated with Alzheimer’s disease, vascular dementia, stroke, coronary heart disease, and heart failure. Kaplan–Meier curves showed higher cumulative incidence across increasing CLivD quartiles, and most dose–response associations were nonlinear. Conclusions Higher CLivD scores identified individuals at increased risk of dementia, cardiovascular disease, cancer, and all-cause mortality in the general population. These findings support CLivD as a broad risk stratification marker, while its interpretation should account for demographic components embedded in the score and requires validation in more diverse populations.