Liver and Bile

Gut. 2024;73(5):825–34

Armandi A, Sanavia T, Younes R, Caviglia GP, Rosso C, Govaere O, Liguori A, Francione P, Gallego-Duràn R, Ampuero J, Pennisi G, Aller R, Tiniakos D, Burt A, David E, Vecchio F, Maggioni M, Cabibi D, McLeod D, Pareja MJ, Zaki MYW, Grieco A, Stål P, Kechagias S, Fracanzani AL, Valenti L, Miele L, Fariselli P, Eslam M, Petta S, Hagström H, George J, Schattenberg JM, Romero-Gómez M, Anstee QM, Bugianesi E

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

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. The authors assessed the role of serum ferritin in predicting long-term outcomes or death.
Design: They 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 5-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 hazard ratio [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 metabolic dysfunction-associated steatotic liver disease.

DOI: 10.1136/gutjnl-2023-330815