Serum Ferritin Levels Lack Diagnostic Accuracy for Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Abstract

Background & Aim Series studies have associated increased serum levels of ferritin with liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the accuracy with which measurements of serum ferritin determine the presence and severity of liver fibrosis, and whether combining noninvasive scoring systems with serum ferritin analysis increases the accuracy of diagnosis of advanced liver fibrosis. Methods We performed a retrospective analysis of data from 1014 patients with liver biopsy-confirmed NAFLD. Three cut-points of serum ferritin level, adjusted for sex, were established based on receiver operating characteristics curve analysis: 1.0 (the upper limit of normal [ULN]), 1.5-fold ULN, and 2.0-fold ULN. Three multiple logistic regression models were created to determine the association of these cutoff values with liver fibrosis, adjusting for age, sex, race, diabetes, body mass index, and level of alanine aminotransferase. Results A greater proportion of patients with increased serum levels of ferritin had definitive NASH and more-advanced fibrosis than patients without increased levels. In all models, serum level of ferritin was significantly associated with the presence and severity of liver fibrosis. However, for all 3 cutoff values, area under the receiver operating characteristic curve values were low (less than 0.60) for the presence of fibrosis or any stage of liver fibrosis; ferritin level identified patients with fibrosis with 16%–41% sensitivity and 70%–92% specificity. The accuracy with which noninvasive scoring systems identified patients with advanced fibrosis did not change with inclusion of serum ferritin values. Conclusions Although serum levels of ferritin correlate with more-severe liver fibrosis, based on adjusted multiple logistic regression analysis, serum ferritin levels alone have a low level of diagnostic accuracy for the presence or severity of liver fibrosis in patients with NAFLD.

Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease

“…Although it is known that ferritin is an acute-phase protein that can be increased in the context of systemic inflammation [45], it is not clear whether rifaximin can act directly on ferritin. Several studies using larger sample populations have shown that increased serum ferritin concentrations are associated with an increased risk of metabolic syndrome and diabetes [46,47].…”

Hyperferritinemia in patients with nonalcoholic fatty liver disease

“…23,27 Nevertheless, it was observed that noninvasive scores have diagnostic accuracy to distinguish between the presence or absence of advanced fibrosis, which did not increase with the addition of ferritin as a variable. 1 Cippà et al considered HPF as a predictor of hemochromatosis only for values above 2,000 mg/L. 23 Angulo et al showed that ferritin correlates positively with fibrosis severity but cannot be used to diagnose the presence or severity of liver fibrosis.…”

“…23 Angulo et al showed that ferritin correlates positively with fibrosis severity but cannot be used to diagnose the presence or severity of liver fibrosis. 1 The manifestations of MetS are influenced by visceral adiposity (VA), but unlike hyperinsulinemia and IR, VA does not determine greater severity of liver damage in patients with NAFLD. In contrast, adiponectin, an insulin-sensitizing adipokine characteristically decreased in obesity, is an independent risk factor for NAFLD.…”

“…It is therefore a marker that allows to discriminate patients who must undergo liver biopsy, pointing out any association with inflammation and fibrosis. Angulo et al 1 assessed the accuracy of serum ferritin and its association with noninvasive scores (NAFLD fibrosis score, BARD, APRI and FIB-4) to determine the presence and severity of liver fibrosis. They retrospectively studied 1,014 patients undergoing liver biopsy and concluded that serum ferritin levels identify fibrosis with 16-41% sensitivity and 70-92% specificity, and correlate positively with fibrosis severity (p<0.001).…”

“…1,2 NAFLD is the most common cause of liver disease today. The spectrum includes steatosis and steatohepatitis (nonalcoholic steatohepatitis, NASH) with increased potential for fibrosis, cirrhosis and hepatocellular carcinoma, and is often associated with increased cardiovascular risk.…”