Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease.

Abstract

OBJECTIVE:

Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death.

DESIGN:

We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate.

RESULTS:

Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 µg/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 µg/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 µg/L and 272 µg/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65).

CONCLUSIONS:

This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.

• Authors: Angelo Armandi, Tiziana Sanavia, Ramy Younes, Gian Paolo Caviglia, Chiara Rosso, Olivier Govaere, Antonio Liguori, Paolo Francione, Rocìo Gallego-Duràn, Javier Ampuero, Grazia Pennisi, Rocio Aller, Dina Tiniakos, Alastair Burt, Ezio David, Fabio Vecchio, Marco Maggioni, Daniela Cabibi, Duncan McLeod, Maria Jesus Pareja, Marco Y W Zaki, Antonio Grieco, Per Stål, Stergios Kechagias, Anna Ludovica Fracanzani, Luca Valenti, Luca Miele, Piero Fariselli, Mohammed Eslam, Salvatore Petta, Hannes Hagström, Jacob George, Jörn M Schattenberg, Manuel Romero-Gómez, Quentin Mark Anstee, Elisabetta Bugianesi
• Journal: Gut (Gut) Vol. 73 Issue 5 Pg. 825-834 (Apr 05 2024) ISSN: 1468-3288 [Electronic] England
• PMID: 38199805 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Ferritins

Topics

• Humans
• Non-alcoholic Fatty Liver Disease (pathology)
• Liver Cirrhosis (pathology)
• Fibrosis
• Metabolic Diseases
• Liver Neoplasms (complications)
• Ferritins