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Abstract Details
Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease
J Hepatol. 2021 Jun 3;S0168-8278(21)00343-3. doi: 10.1016/j.jhep.2021.05.008.Online ahead of print.
Ramy Younes1, Gian Paolo Caviglia2, Olivier Govaere3, Chiara Rosso2, Angelo Armandi2, Tiziana Sanavia2, Grazia Pennisi4, Antonio Liguori5, Paolo Francione6, Rocío Gallego-Durán7, Javier Ampuero7, Maria J Garcia Blanco8, Rocio Aller9, Dina Tiniakos10, Alastair Burt3, Ezio David11, Fabio M Vecchio12, Marco Maggioni13, Daniela Cabibi14, María Jesús Pareja15, Marco Y W Zaki16, Antonio Grieco17, Anna L Fracanzani6, Luca Valenti18, Luca Miele17, Piero Fariselli2, Salvatore Petta4, Manuel Romero-Gomez7, Quentin M Anstee19, Elisabetta Bugianesi20
Author information
1The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Boehringer Ingelheim International, GmbH, Ingelheim, Germany.
2Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
3The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
4Sezione di Gastroenterologia, PROMISE, Università di Palermo, Palermo, Italy.
5Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
6Unit of Medicine and Metabolic Disease Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan Italy.
7UCM Digestive Diseases and SeLiver Group, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Spain.
8Hospital Universitario de La Princesa, Medicina Interna, Madrid, Spain.
9Hospital Clínico de Valladolid, Valladolid, Spain.
10The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Dept of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
11Department of Pathology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy.
12Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; Area Anatomia Patologica. Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
13Department of Pathology, Ca' Granda IRCCS Foundation, Milan, Italy.
14Pathology Institute, PROMISE, University of Palermo, Palermo, Italy.
15Pathology Unit, Valme University Hospital, Seville, Spain.
16The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Biochemistry Department, Faculty of Pharmacy, Minia University, Egypt.
17Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; Area Medicina Interna, Gastroenterologia e Oncologia Medica, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
18Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
19The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address: quentin.anstee@ncl.ac.uk.
20Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. Electronic address: elisabetta.bugianesi@unito.it.
Abstract
Background & aims: Non-Invasive Scoring Systems (NSS) are used to identify NAFLD patients at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extra-hepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain.
Methods: The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet Fibrosis Score (HFS) were assessed in 1,173 NAFLD European patients from tertiary centres. Performance in fibrosis risk stratification and prediction ability of long-term hepatic/extra-hepatic events, hepatocarcinoma (HCC) and overall mortality was evaluated in terms of area under the curve (AUC) and Harrell's C-index. For longitudinal data, NSS-based Cox proportional hazard models were trained on the whole cohort with repeated 5-fold cross validation, sampling for testing from the 607 patients with all NSS available.
Results: Cross-sectional analysis revealed HFS as the best performer for the identification of significant (F0-1 vs F2-4, AUC=0.758) and advanced fibrosis (F0-2 vs F3-4, AUC=0.805), while NFS and FIB-4 showed the highest performance in detecting histological cirrhosis (range AUCs 0.85-0.88). Considering longitudinal data (follow-up between 62 and 110 months), NFS and FIB-4 were the best at predicting liver-related events (c-indices>0.7), NFS for HCC (c-index=0.9 on average), while FIB-4 and HFS for overall mortality (c-indices>0.8). All NSS showed scarce performance (c-indices<0.7) for extra-hepatic events.
Conclusions: Overall, NFS, HFS and FIB-4 outperformed APRI and BARD in both cross-sectional identification of fibrosis and prediction of long-term outcomes, showing to be useful tools for clinicians in managing NAFLD patients at increased fibrosis risk and liver-related complications or death.