Assessing whether serum ceruloplasmin promotes non-alcoholic steatohepatitis via regulating iron metabolism

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). The diagnostic gold standard for detecting NASH still relies upon an invasive pathological biopsy. There is, therefore, a need to identify non-invasive diagnostic markers. Oxidative stress mediates fatty liver progression to NASH. Imbalanced iron metabolism produces many reactive oxygen species (ROS). Ceruloplasmin is associated with oxidase and iron metabolism-related activities. The current study aimed to determine whether there was a correlation between ceruloplasmin levels and NASH and whether such a relationship may be associated with altered iron metabolism in NASH patients. Methods: A total of 135 NAFLD patients were enrolled in this study. A pathological biopsy confirmed that 60 of those patients had NAFLD activity scores (NAS) 5, while the remaining 75 had NAS<5. Results: Receiver operating characteristic (ROC) curves confirmed that serum ceruloplasmin and ferritin levels were predictors of NAS 5 and NAS<5, with area under the curve (AUC) values of 0.80 and 0.81, respectively. The serum ceruloplasmin levels in NAS 5 patients were significantly lower than those in NAS<5 patients (p< 0.001). Serum ceruloplasmin levels were also negatively correlated with ferritin levels. Lower serum ceruloplasmin levels were associated with more severe histopathological findings. Conclusions: Low serum ceruloplasmin and high serum ferritin are correlated with NASH. A high concentration of serum ferritin is a viable clinical biomarker of NASH, and low serum ceruloplasmin may participate in the occurrence of NASH by regulating iron load, which can be used as a non-invasive diagnostic marker of NASH.