Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease
Open accessAbstract
Background & aims Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic 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 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of 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 (F0-2 vs. F3-4, AUC = 0.805) fibrosis, while NFS and FIB-4 showed the best performance for 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), and FIB-4 and HFS for overall mortality (c-indices >0.8). All NSS showed limited performance (c-indices <0.7) for extrahepatic events.Conclusions Overall, NFS, HFS and FIB-4 outperformed APRI and BARD for both cross-sectional identification of fibrosis and prediction of long-term outcomes, confirming that they are useful tools for the clinical management of patients with NAFLD at increased risk of fibrosis and liver-related complications or death.Lay summary Non-invasive scoring systems are increasingly being used in patients with non-alcoholic fatty liver disease to identify those at risk of advanced fibrosis and hence clinical complications. Herein, we compared various non-invasive scoring systems and identified those that were best at identifying risk, as well as those that were best for the prediction of long-term outcomes, such as liver-related events, liver cancer and death.
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Retrospective analyses have provided further evidence of the potential of FIB-4, NFS and ELF to predict progression to cirrhosis and liver-related events.
“Retrospective analyses have provided further evidence of the potential of FIB-4, NFS and ELF to predict progression to cirrhosis and liver-related events. 181,182”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [182]
The Results (p. 4) report that FIB-4 and NFS detected histological cirrhosis and were the best predictors of subsequent liver-related events. The paper does not evaluate ELF, and its cirrhosis-detection analysis was cross-sectional rather than a longitudinal test of progression to cirrhosis (Statistical Analysis, p. 9). (LLM, conf=0.88)
Experimental — accuracy not yet measuredNAFLD fibrosis score (NFS) has a reported c-index of up to 0.9 for the prediction of HCC in a longitudinal study of 1,173 European individuals with MASLD.
“The NAFLD fi brosis score (NFS) had a reported c-index of up to 0.9 for the prediction of HCC in a longitudinal study of 1,173 European individuals with MASLD. 182”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [182]
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- Authors
- Younes, R., Caviglia, G. P., Govaere, O., Rosso, C., Armandi, A., Sanavia, T., Pennisi, G., Liguori, A., Francione, P., Gallego-Durán, R., Ampuero, J., Garcia Blanco, M. J., Aller, R., Tiniakos, D., Burt, A., David, E., Vecchio, F. M., Maggioni, M., Cabibi, D., Pareja, M. J., Zaki, M. Y. W., Grieco, A., Fracanzani, A. L., Valenti, L., Miele, L., Fariselli, P., Petta, S., Romero-Gomez, M., Anstee, Q. M., & Bugianesi, E.
- Affiliations
- Boehringer Ingelheim (Germany) (DE)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Newcastle University (GB)
- University of Palermo (IT)
- Università Cattolica del Sacro Cuore (IT)
- University of Milan (IT)
- Instituto de Biomedicina de Sevilla (ES)
- Hospital Clínico Universitario de Valladolid (ES)
- National and Kapodistrian University of Athens (GR)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Hospital Universitario de Valme (ES)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Anstee, Quentin M.
- Bugianesi, Elisabetta
- ORCID
- Younes, Ramy
- Caviglia, Gian Paolo
- Govaere, Olivier
- Rosso, Chiara
- Armandi, Angelo
- Sanavia, Tiziana
- Pennisi, Grazia
- Liguori, Antonio
- Ampuero, Javier
- Garcia Blanco, Maria J.
- Aller, Rocio
- Tiniakos, Dina
- Burt, Alastair
- David, Ezio
- Maggioni, Marco
- Cabibi, Daniela
- Pareja, María Jesús
- Zaki, Marco Y.W.
- Grieco, Antonio
- Fracanzani, Anna L.
- Valenti, Luca
- Miele, Luca
- Fariselli, Piero
- Petta, Salvatore
- Anstee, Quentin M.
- Bugianesi, Elisabetta
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 75
- Issue
- 4
- Pages
- 786-794
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W3162991784
- Cited by
- 196
- References
- 29
- Citations by year
- 2026: 23 · 2025: 34 · 2024: 38 · 2023: 44 · 2022: 47 · 2021: 8
- FWCI
- 24.67
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
- Funders
- MIUR
- Ministero della Salute
- Horizon 2020
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, liver fibrosis, FIB-4, APRI, bards, NAFLD fibrosis score, hepatocellular carcinoma, liver-related mortality, extrahepatic complications, long-term outcomes, risk prediction, liver cirrhosis, prognostic performance
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Humans, Liver, Male, Middle Aged, Predictive Value of Tests, Prognosis, Research Design, ROC Curve, Severity of Illness Index, Time, Reproducibility of Results, Area Under Curve, Non-alcoholic Fatty Liver Disease
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