Liver and Bile

Lancet. 2023;402(10406):988–96

Serra-Burriel M, Juanola A, Serra-Burriel F, Thiele M, Graupera I, Pose E, Pera G, Grgurevic I, Caballeria L, Piano S, van Kleef L, Reichert M, Roulot D, Pericàs JM, Schattenberg JM, Tsochatztis EA, Guha IN, Garcia-Retortillo M, Hernández R, Hoyo J, Fuentes M, Expósito C, Martínez A, Such P, Madir A, Detlefsen S, Tonon M, Martini A, Ma AT, Pich J, Bonfill E, Juan M, Soria A, Carol M, Gratacós-Ginès J, Morillas RM, Toran P, Navarrete JM, Torrejón A, Fournier C, Llorca A, Arslanow A, de Koning HJ, Cucchietti F, Manns M, Newsome PN, Hernáez R, Allen A, Angeli P, de Knegt RJ, Karlsen TH, Galle P, Wong VWS, Fabrellas N, Castera L, Krag A, Lammert F, Kamath PS, Ginès P; LiverScreen Consortium Investigators

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: A multicohort study

Background: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. The aim of this study was to develop a novel score to identify individuals at risk for future liver-related outcomes.
Methods: The LiverRisk score was derived from an international prospective cohort of individuals from 6 countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and 6 standard laboratory variables. The authors created 4 groups: minimal risk, low risk, medium risk, and high risk according to selected cut-off values of the LiverRisk score (6, 10, and 15). The model’s discriminatory accuracy and calibration were externally validated in 2 prospective cohorts from the general population. Moreover, they ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort).
Findings: 14,726 participants were included: 6357 (43.2%) in the derivation cohort, 4370 (29.7%) in the first external validation cohort, and 3999 (27.2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC: 0.83 [95% confidence interval {CI}: 0.78–0.89]) versus the fibrosis-4 index (FIB-4; AUC: 0.68 [95% CI: 0.61–0.75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalization, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI: 347–641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0.90 (95% CI: 0.88–0.91) versus 0.84 (95% CI: 0.82–0.86) for FIB-4.

Interpretation: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care.

DOI: 10.1016/s0140-6736(23)01174-1