Hyperferritinemia and the Risk of Liver Fibrosis and Liver-Related Events in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease

高铁蛋白血症与2型糖尿病和代谢功能障碍相关脂肪肝患者发生肝纤维化和肝脏相关事件的风险

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Abstract

Background and Objectives: This study evaluated the correlation between hyperferritinemia and markers of liver steatosis, fibrosis, and risk of liver-related events in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Material and Methods: This study included 271 patients that underwent a comprehensive medical evaluation. Hyperferritinemia was defined by values >200 ng/mL (females) and >300 ng/mL (males). Liver fibrosis and steatosis were evaluated by several non-invasive indexes, and Liver Risk Score (LRS) was calculated to determine the risk of liver-related events. Their correlation with serum ferritin was investigated by bivariate and multiple regression analyses. Receiver Operating Characteristic (ROC) analyses were used to assess the accuracy to predict advanced fibrosis and increased LRS. Statistical significance was set at p < 0.05. Results: The median serum ferritin level was 94.4 [128.1] ng/mL. Metabolic hyperferritinemia was present in 12.54% of patients. Patients with hyperferritinemia had higher liver enzymes, HbA1c, HOMA-IR, and increased markers of liver steatosis and fibrosis, with a higher prevalence of advanced fibrosis (OR = 3.744 [1.481, 9.460], p = 0.0081). LRS was highest in patients with hyperferritinemia (7.99 ± 2.01 vs. 7.12 ± 1.32 vs. 6.54 ± 1.06, p < 0.0001). Serum ferritin levels were correlated with LRS (β = 0.190 [0.001; 0.003], p < 0.001), liver fibrosis (Fibrotic NASH Index) (β = 0.198 [0.000; 0.001], p < 0.001), and steatosis, while haptoglobin concentrations were correlated negatively with them. Serum ferritin predicted the moderate risk of liver-related outcomes with an acceptable performance (area under the ROC curve = 0.726 [0.590; 0.862], p = 0.001). Conclusions: Hyperferritinemia is associated with liver fibrosis and steatosis and a higher risk of liver-related events in patients with T2DM and MASLD.

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