Geisinger Commonwealth School of Medicine Scranton, PA
Introduction: Increased serum ferritin is a commonly used blood test that reflects iron stores including liver iron overload. However, the interpretation of ferritin levels is influenced both by iron stores and inflammation. In patients with obesity, ferritin levels may be elevated with iron overload and with inflammation. This study investigated the clinical factors associated with hyperferritinemia in patients with severe obesity and hepatic iron overload.
Methods: This study included 4359 patients that had a wedge liver biopsy and documented pre-operative serum ferritin at time of primary metabolic surgery between 2004 and 2021. The standard Perls’/Prussian Blue iron stain was used to diagnose hepatic iron overload. Patients with iron deficiency (ferritin< 30 ng/ml) and extremely high ferritin levels (ferritin >1000 ng/ml) were excluded. Elevated ferritin was defined as 300-999 ng/ml in males and 200-999 ng/ml in females. Clinical data collected on each patient included sex, age, BMI, race/ethnicity, smoking, transferrin saturation, diabetes, hypertension, hyperlipidemia, liver steatosis, liver fibrosis, and type of cells involved in liver iron overload. Multiple logistic regression was used to determine which clinical factors were independently associated with elevated ferritin.
Results: The 4351 metabolic surgery patients included 703 (16%) with hepatic iron overload. These 703 patients included 441 (63%) females with a mean age of 47.8 years (SD=10.6), mean BMI of 47.1 kg/m2 (SD=8.1), and 37% (n=258) with elevated ferritin. The types of cells involved with the liver iron overload included Kupffer (34%), hepatocyte (37%), and both (29%) but cell type was not associated with elevated ferritin (p=0.317). Factors that were independently related to high ferritin included increasing levels of steatosis, increasing level of fibrosis, presence of hypertension, normal transferrin saturation (≥20%), male sex, and age 40-59 years (see Table).
Discussion: The histopathological and demographic parameters significantly associated with hyperferritinemia in metabolic surgery patients with hepatic iron overload suggest the role of ferritin in clinical evaluation. The results support the potential association of chronic low-grade systemic inflammation with steatosis, fibrosis, and hypertension when differentiating between hyperferritinemia and normal ferritin levels in patients with severe obesity and excess hepatic iron.
