Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD), defined by excessive liver fat deposition related to the metabolic syndrome, is a leading cause of progressive liver disease, for which accurate non-invasive staging systems and effective treatments are still lacking. Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome, and higher hepatic iron and fat content. Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD, and iron depletion reduced insulin resistance and liver enzymes. Recently, Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD, and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis. These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD, and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.

Keywords: Ferritin; Fibrosis; Iron overload; Nonalcoholic fatty liver disease; Steatohepatitis; Steatosis.

Figure 1

Proposed mechanisms explaining iron induced liver damage associated with steatosis and hepatic iron overload in hepatocytes (brown), macrophages (grey), and hepatic stellate cells (yellow). Cp: Ceruloplasmin; Fe-Tf: Ferric-transferrin; Fp-1: Ferroportin-1; HCC: Hepatocellular carcinoma; HFE: Hemochromatosis gene; HSCs: Hepatic stellate cells; MDA: Malonyl-dialdehyde; ROS: Reactive oxygen species; SOD2: Mn superoxide dismutase; Tf-R: Transferrin receptor. Modified from Dongiovanni et al[19].