Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease

Ramy Younes, Gian Paolo Caviglia, Olivier Govaere, Chiara Rosso, Angelo Armandi, Tiziana Sanavia, Grazia Pennisi, Antonio Liguori, Paolo Francione, Rocío Gallego-Durán, Javier Ampuero, Maria J. Garcia Blanco, Rocio Aller, Dina Tiniakos, Alastair Burt, Ezio David, Fabio M. Vecchio, Marco Maggioni, Daniela Cabibi, María Jesús ParejaMarco Y.W. Zaki, Antonio Grieco, Anna L. Fracanzani, Luca Valenti, Luca Miele, Piero Fariselli, Salvatore Petta, Manuel Romero-Gomez, Quentin M. Anstee, Elisabetta Bugianesi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)786-794
JournalJournal of Hepatology
Issue number4
Publication statusPublished - 2021


  • APRI
  • BARD
  • FIB-4
  • HFS
  • NASH
  • NFS
  • NSS

ASJC Scopus subject areas

  • Hepatology


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