. 2024 Apr 5;73(5):825-834.

doi: 10.1136/gutjnl-2023-330815.

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

Angelo Armandi^#^{1

2}, Tiziana Sanavia^#³, Ramy Younes⁴, Gian Paolo Caviglia⁵, Chiara Rosso⁵, Olivier Govaere⁶, Antonio Liguori^{7

8

9}, Paolo Francione¹⁰, Rocìo Gallego-Duràn¹¹, Javier Ampuero¹¹, Grazia Pennisi¹², Rocio Aller¹³, Dina Tiniakos^{6

14}, Alastair Burt⁶, Ezio David¹⁵, Fabio Vecchio¹⁶, Marco Maggioni¹⁷, Daniela Cabibi¹⁸, Duncan McLeod¹⁹, Maria Jesus Pareja²⁰, Marco Y W Zaki^{6

21

22}, Antonio Grieco²³, Per Stål^{24

25}, Stergios Kechagias²⁶, Anna Ludovica Fracanzani^{10

27}, Luca Valenti^{27

28}, Luca Miele^{7

8

9}, Piero Fariselli³, Mohammed Eslam²⁹, Salvatore Petta¹², Hannes Hagström^{24

25}, Jacob George²⁹, Jörn M Schattenberg^{2

30}, Manuel Romero-Gómez¹¹, Quentin Mark Anstee^{6

31}, Elisabetta Bugianesi⁵

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy angelo.armandi@unito.it.
² Metabolic Liver Disease Research Program, I. Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Computational Biomedicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy.
⁴ Boehringer Ingelheim International GmbH, Ingelheim, Germany.
⁵ Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy.
⁶ Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
⁷ Internal Medicine and Liver Transplant Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁸ CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁹ Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
¹⁰ Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹¹ UCM Digestive Diseases and SeLiver Group, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain.
¹² Sezione di Gastroenterologia, PROMISE, Università di Palermo, Palermo, Italy.
¹³ Hospital Clínico de Valladolid, Valladolid, Spain.
¹⁴ Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹⁵ Department of Pathology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy.
¹⁶ Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Area Anatomia Patologica. Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
¹⁷ Department of Pathology, Ca' Granda IRCCS Foundation, Milan, Italy.
¹⁸ Pathology Institute, PROMISE, University of Palermo, Palermo, Italy.
¹⁹ Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia.
²⁰ Pathology Unit, Hospital Universitario de Valme, Seville, Spain.
²¹ Biochemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
²² Centre for Research and Sustainability, Deraya University, New Minia, Minia, Egypt.
²³ Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
²⁴ Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
²⁵ Department of Medicine, Huddinge Karolinska Institutet, Stockholm, Sweden.
²⁶ Department of Health, Medicine and Caring Sciences, Linköping University, Linkoping, Sweden.
²⁷ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
²⁸ Biological Resource Center Unit and Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
²⁹ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
³⁰ Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
³¹ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

^# Contributed equally.

PMID: 38199805
DOI: 10.1136/gutjnl-2023-330815

Free article

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

Angelo Armandi et al. Gut. 2024.

Free article

. 2024 Apr 5;73(5):825-834.

doi: 10.1136/gutjnl-2023-330815.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy angelo.armandi@unito.it.
² Metabolic Liver Disease Research Program, I. Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Computational Biomedicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy.
⁴ Boehringer Ingelheim International GmbH, Ingelheim, Germany.
⁵ Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy.
⁶ Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
⁷ Internal Medicine and Liver Transplant Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁸ CEMAD, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁹ Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
¹⁰ Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹¹ UCM Digestive Diseases and SeLiver Group, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain.
¹² Sezione di Gastroenterologia, PROMISE, Università di Palermo, Palermo, Italy.
¹³ Hospital Clínico de Valladolid, Valladolid, Spain.
¹⁴ Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
¹⁵ Department of Pathology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy.
¹⁶ Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Area Anatomia Patologica. Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
¹⁷ Department of Pathology, Ca' Granda IRCCS Foundation, Milan, Italy.
¹⁸ Pathology Institute, PROMISE, University of Palermo, Palermo, Italy.
¹⁹ Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia.
²⁰ Pathology Unit, Hospital Universitario de Valme, Seville, Spain.
²¹ Biochemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
²² Centre for Research and Sustainability, Deraya University, New Minia, Minia, Egypt.
²³ Dipartimento Universitario Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
²⁴ Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
²⁵ Department of Medicine, Huddinge Karolinska Institutet, Stockholm, Sweden.
²⁶ Department of Health, Medicine and Caring Sciences, Linköping University, Linkoping, Sweden.
²⁷ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
²⁸ Biological Resource Center Unit and Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
²⁹ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
³⁰ Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
³¹ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

^# Contributed equally.

PMID: 38199805
DOI: 10.1136/gutjnl-2023-330815

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.

Keywords: FIBROSIS; NONALCOHOLIC STEATOHEPATITIS.

PubMed Disclaimer

Conflict of interest statement

Competing interests: LM is supported by Investigator Driven Grants: Gilead, Intercept, Siemens Healthineers. Advisor/Consultancy: Alfa-Sigma, Boehringer-Ingelheim, BMS, Echosens, Galmed, Gilead Sciences, IBSA, Intercept, MEDA, MyGenomics, Merck Sharp & Dohme, Novartis, Pfizer, ProLon, Promethera, Resalis, Rottapharm-Madaus, Siemens Healthineers, Synageva. HH’s institutions have received research funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer. He has served as consultant or on advisory boards for Astra Zeneca, Bristol Myers-Squibb, MSD and Novo Nordisk and has been part of hepatic events adjudication committees for Boehringer Ingelheim, KOWA and GW Pharma.

Comment in

Ferritin-a promising biomarker in MASLD.
Zoller H, Tilg H. Zoller H, et al. Gut. 2024 Apr 5;73(5):720-721. doi: 10.1136/gutjnl-2023-331848. Gut. 2024. PMID: 38538068 No abstract available.
The validity of serum ferritin levels in predicting cardiovascular events of metabolic dysfunction-associated steatotic liver disease patients may need more consideration.
Yang J, Liu Q, Li J, Sun C. Yang J, et al. Hepatobiliary Surg Nutr. 2024 Aug 1;13(4):755-756. doi: 10.21037/hbsn-24-217. Epub 2024 Jul 22. Hepatobiliary Surg Nutr. 2024. PMID: 39175730 Free PMC article. No abstract available.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- HighWire
- Ovid Technologies, Inc.
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical