| Title: | Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study |
| Journal: | The Lancet |
| Published: | 9 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37572680/ |
| DOI: | https://doi.org/10.1016/s0140-6736(23)01174-1 |
Publication 10175
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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.</p>
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).</p>
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.</p>
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.</p>
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).</p>
177 Authors
- Miquel Serra-Burriel
- Adrià Juanola
- 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 Hernández
- Jordi Hoyo
- Matilde Fuentes
- Carmen Expósito
- Alba Martínez
- Patricia Such
- Anita Madir
- Sönke Detlefsen
- Marta Tonon
- Andrea Martini
- Ann T
- 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
- Michael Manns
- Phillip N Newsome
- Rubén Hernáez
- Alina Allen
- Paolo Angeli
- Robert J de Knegt
- Tom H Karlsen
- Peter Galle
- Vincent Wai-Sun Wong
- Núria Fabrellas
- Laurent Castera
- Aleksander Krag
- Frank Lammert
- Patrick S Kamath
- Pere Ginès
- LiverScreen Consortium Investigators
- Marifé Alvarez
- Peter Andersen
- Paolo Angeli
- Alba Ardèvol
- Anita Arslanow
- Luca Beggiato
- Zahia Ben Abdesselam
- Lucy Bennett
- Bajiha Boutouria
- Alessandra Brocca
- M. Teresa Broquetas
- Llorenç Caballeria
- Valeria Calvino
- Judith Camacho
- Aura Capdevila
- Marta Carol
- Laurent Castera
- Marta Cervera
- Fernando Cucchietti
- Anna de Fuentes
- Rob de Knegt
- Harry J de Koning
- Sonke Detlefsen
- Alba Diaz
- José Diéguez Bande
- Vanessa Esnault
- Núria Fabrellas
- Josep Lluis Falcó
- Rosa Fernández
- Céline Fournier
- Matilde Fuentes
- Peter Galle
- Edgar García
- Montserrat García-Retortillo
- Esther Garrido
- Pere Ginès
- Rosa Gordillo Medina
- Jordi Gratacós-Ginès
- Isabel Graupera
- Ivica Grgurevic
- Indra Neil Guha
- Eva Guix
- Johanne Kragh Hansen
- Rebecca Harris
- Elena Hernández Boluda
- Rosario Hernández-Ibañez
- Jordi Hoyo
- Arfan Ikram
- Simone Incicco
- Mads Israelsen
- Marta Juan
- Adrià Juanola
- Ralf Kaiser
- Patrick S Kamath
- Tom H Karlsen
- Maria Kjærgaard
- Marko Korenjak
- Aleksander Krag
- Marcin Krawczyk
- Philippe Laboulaye
- Irina Lambert
- Frank Lammert
- Simon Langkjær Sørensen
- Cristina Laserna-Jiménez
- Sonia Lazaro Pi
- Elsa Ledain
- Vincent Levy
- Katrine Prier Lindvig
- Anne Llorca
- Vanessa Londoño
- Guirec Loyer
- Ann T.
- Anita Madir
- Michael Manns
- Denise Marshall
- M. Lluïsa Martí
- Sara Martínez
- Ricard Martínez Sala
- Roser Masa-Font
- Jane Møller Jensen
- Rosa M Morillas
- Laura Muñoz
- Ruth Nadal
- Laura Napoleone
- JM Navarrete
- Phillip N Newsome
- Vibeke Nielsen
- Martina Pérez
- Juan Manuel Pericás-Pulido
- Salvatore Piano
- Judit Pich
- Elisa Pose
- Judit Presas Escobet
- Matthias Reichert
- Carlota Riba
- Dominique Roulot
- Ana Belén Rubio
- Maria Sánchez-Morata
- Jörn Schattenberg
- Miquel Serra-Burriel
- Feliu Serra-Burriel
- Louise Skovborg Just
- Milan Sonneveld
- Anna Soria
- Christiane Stern
- Patricia Such
- Maja Thiele
- Marta Tonon
- Pere Toran
- Antoni Torrejón
- Emmanuel A Tsochatzis
- Laurens van Kleef
- Paulien van Wijngaarden
- Vanessa Velázquez
- Ana Viu
- Susanne Nicole Weber
- Tracey Wildsmith
Enabling scientific discoveries that improve human health