Serum Ferritin Is An Independent Predictor of Histologic... : Hepatology (original) (raw)

Liver Biology/Pathobiology

Serum Ferritin Is An Independent Predictor of Histologic Severity and Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Kowdley, Kris V.1,7,*,†; Belt, Patricia2; Wilson, Laura A.2; Yeh, Matthew M.3; Neuschwander–Tetri, Brent A.4; Chalasani, Naga5; Sanyal, Arun J.6; Nelson, James E.7 for the NASH Clinical Research Network.

1_Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA_

2_Johns Hopkins University School of Public Health, Baltimore, MD_

3_University of Washington Medical Center, Seattle, WA_

4_Saint Louis University, St Louis, MO_

5_Indiana University, Indianapolis, IN_

6_Virginia Commonwealth University, Richmond, VA_

7_Benaroya Research Institute at Virginia Mason Medical Center, Seattle, WA_

*Address reprint requests to: Benaroya Research Institute and Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA 98101

Email: [email protected]

Received 5 August 2011; Accepted 26 September 2011

Grant sponsor: Intramural Research Program of the National Cancer Institute; Grant sponsor: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN); Grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Grant Numbers: U01DK061718 U01DK061728 U01DK061731 U01DK061732 U01DK061734 U01DK061737 U01DK061738 U01DK061730 U01DK061713; Grant sponsor: National Institute of Child Health and Human Development; Grant sponsor: National Institutes of Health; Grant Numbers: K24DK002957 R56DK087696; Grant sponsor: General Clinical Research Centers or Clinical and Translational Science Awards in conduct of NASH CRN Studies; Grant Numbers: UL1RR024989 M01RR000750 M01RR00188 UL1RR02413101 M01RR000827 UL1RR02501401 M01RR000065 M01RR020359.

Potential conflict of interest: Nothing to report.

†fax: 206–341–1934

Abstract

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥18 years) with biopsy–proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin–iron saturation, iron stain grade, and decreased platelets ( P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH ( P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05–2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06–3.75; P = 0.033). Conclusions: A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. (Hepatology 2012)