Liver and Bile
Gut. 2024;73(5):825–34
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.