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

Miquel Serra-Burriel, Adrià Juanola, LiverScreen Consortium Investigators, Feliu Serra-Burriel, Maja Thiele, Isabel Graupera, Elisa Pose, Guillem Pera, Ivica Grgurevic, Llorenç Caballeria, Salvatore Piano, Laurens van Kleef, Mathias Reichert, Dominique Roulot, Juan M. Pericàs, Jörn M. Schattenberg, Emmanuel A. Tsochatztis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosario HernándezJordi Hoyo, Matilde Fuentes, Carmen Expósito, Alba Martínez, Patricia Such, Anita Madir, Sönke Detlefsen, Marta Tonon, Andrea Martini, Ann T. Ma, Judith Pich, Eva Bonfill, Marta Juan, Anna Soria, Marta Carol, Jordi Gratacós-Ginès, Rosa M. Morillas, Pere Toran, J. M. Navarrete, Antoni Torrejón, Céline Fournier, Anne Llorca, Anita Arslanow, Harry J. de Koning, Fernando Cucchietti, Rob de Knegt, Lucy Bennett, Arfan Ikram, Milan Sonneveld, Paulien van Wijngaarden

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

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. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. Methods: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we 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: We included 14 726 participants: 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% CI [0·78–0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61–0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, 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 (0·88–0·91) versus 0.84 (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. Funding: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

Original languageEnglish
Pages (from-to)988-996
Number of pages9
JournalThe Lancet
Volume402
Issue number10406
Early online date9 Aug 2023
DOIs
Publication statusPublished - 16 Sept 2023

Bibliographical note

Role of the funding source:
The funders of the study had no role in study design,
data collection, data analysis, data interpretation,
writing, or the decision to submit the report.

Publisher Copyright:
© 2023 Elsevier Ltd

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