Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

Hyperferritinemia in patients with nonalcoholic fatty liver disease

“…Nevertheless, the option of screening and monitoring of NASH and hepatic fibrosis should not be differentiated in lean individuals. 12,27,28 There is controversy regarding the results of phlebotomy to eliminate excess iron. Some believe that there is no improvement in steatosis, liver damage or IR.…”

“…Yoneda et al 12 evaluated serum ferritin dosages, the presence of HFE gene mutations, and insulin resistance in 86 Japanese patients and 20 controls. Study participants had NAFLD on histopathological examination of the liver (24 patients with steatosis and 62 patients with NASH).…”

Usefulness of Magnetic Resonance Imaging for the Diagnosis of Hemochromatosis with Severe Hepatic Steatosis in Nonalcoholic Fatty Liver Disease

“…The complicated pathogenesis of NASH reportedly involves insulin resistance, which is related to the metabolic syndrome, and oxidative damage, which may result from endoplasmic reticulum stress, adipocytokines, endotoxins and/or the degree of hepatic iron accumulation (11). Although its clinical significance and mechanism remain to be clarified, high serum fer-ritin levels are reportedly associated with the pathogenesis of NASH (12). Furthermore, excess iron distributed throughout the liver is common in NASH (13).…”

To Study the Clinical Profile and Viral Markers (Hepatitis B and C) In Acute and Chronic Liver Disease

“…52 The term non-alcoholic fatty liver disease (NAFLD) is used to describe a wide spectrum of fatty liver changes ranging from simple steatosis to steatohepatitis, even to cirrhosis. 53 55 Liver biopsy remains the gold standard in diagnosis and prognosis of NAFLD, but being invasive has limitation for patient consent. Serum ferritin and C-reactive protein (CRP) are nonspecific inflammatory markers, but while it is not specific for diagnosis of NAFLD, once the diagnosis has been established, their level has been shown to be significantly more elevated in patients with NASH compared to with those with simple steatosis (SS).…”