Combined use of the CLivD score and FIB-4 for prediction of liver-related outcomes in the population

Abstract

Background and Aims: A need exists for effective and practical tools to identify individuals at increased risk of liver-related outcomes (LROs) within the general population. Approach and Results: We externally validated the chronic liver disease (CLivD) score for LROs in the UK Biobank cohort. We also investigated the sequential combined use of CLivD and fibrosis-4 (FIB-4) scores. Our analysis included 369,832 adults without baseline liver disease and with available data for CLivD and FIB-4 computation. LROs reflecting compensated or decompensated liver cirrhosis or HCC were ascertained through linkages with electronic health care registries. Discriminatory performance and cumulative incidence were evaluated with competing-risk methodologies. Over a 10-year follow-up, time-dependent AUC values for LRO prediction were 0.80 for CLivDlab (including gamma-glutamyltransferase), 0.72 for CLivDnon-lab (excluding laboratory values), and 0.75 for FIB-4. CLivDlab demonstrated AUC values exceeding 0.85 for liver-related death and severe alcohol-associated liver outcomes. The predictive performance of FIB-4 increased with rising CLivD scores; 10-year FIB-4 AUC values ranged from 0.60 within the minimal-risk CLivD subgroup to 0.81 within the high-risk CLivD subgroup. Moreover, in the minimal-risk CLivD subgroup, the cumulative incidence of LRO varied from 0.05% to 0.3% across low-to-high FIB-4 strata. In contrast, within the high-risk CLivD subgroup, the corresponding incidence ranged from 1.7% to 21.1% (up to 33% in individuals with FIB-4 >3.25). Conclusions: The CLivD score is a valid tool for LRO risk assessment and improves the predictive performance of FIB-4. The combined use of CLivD and FIB-4 identified a subgroup where 1 in 3 individuals developed LROs within 10 years.