Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease

Authors

  • James E. Nelson,

    1. Benaroya Research Institute, Digestive Disease Institute, Virginia Mason Medical Center, Seattle WA
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  • Laura Wilson,

    1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • Elizabeth M. Brunt,

    1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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  • Matthew M. Yeh,

    1. Department of Pathology, University of Washington Medical Center, Seattle WA
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  • David E. Kleiner,

    1. Laboratory of Pathology, National Cancer Institute, Bethesda, MD
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  • Aynur Unalp-Arida,

    1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • Kris V. Kowdley

    Corresponding author
    1. Benaroya Research Institute, Digestive Disease Institute, Virginia Mason Medical Center, Seattle WA
    2. Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, Seattle WA
    • Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, 1201 Ninth Ave Seattle WA 98101
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    • fax: 206-341-1934

    • The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713) and by the National Institute of Child Health and Human Development. Kris V. Kowdley is supported by the National Institutes of Health (K24 grant DK-02957). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards to conduct studies for the Nonalcoholic Steatohepatitis Clinical Research Network (grants UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065, and M01RR020359). This work was supported in part by the Intramural Research Program of the National Cancer Institute.


  • Potential conflict of interest: Nothing to report.

  • A list of the members of the Nonalcoholic Steatohepatitis Clinical Research Network can be found in the supporting information.

Abstract

Previous studies examining the relationship between hepatic iron deposition and histological severity in nonalcoholic fatty liver disease (NAFLD) have been inconclusive. The goal of this study was to examine the relationship between hepatic iron deposition and liver histology in 849 patients enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Hepatic iron staining was performed in a central laboratory, and the stains were scored for grade and cellular and parenchymal localization by a central pathology committee; the relationship between the grade and pattern of iron deposition and the clinical, laboratory, and histological variables was examined with univariate and multivariate analyses. Stainable hepatic iron was present in 293 of 849 patients (34.5%) in one of three histological patterns: a hepatocellular (HC) pattern [63/849 (7.4%)], a reticuloendothelial system (RES) cell pattern [91/849 (10.7%)], or a mixed RES/HC pattern [139/849 (16.4%)]. Patients with the RES iron-staining pattern were more likely to have advanced fibrosis compared to those with those with HC iron (P = 0.01). Patients with RES iron were also more likely to have advanced histological features such as fibrosis (P = 0.049), portal inflammation (P = 0.002), HC ballooning (P = 0.006), and definite nonalcoholic steatohepatitis (P = 0.007) compared to those with patients with HC or mixed iron patterns. The presence of RES iron (odds ratio = 1.60, 95% confidence interval = 1.10-2.33, P = 0.015) was independently associated with advanced hepatic fibrosis on multiple regression analysis after adjustments for age, gender, diabetes status, and body mass index. Conclusion: The presence and pattern of hepatic iron deposition are associated with distinct histological features in patients with NAFLD and may have implications for pathophysiology and therapy. (HEPATOLOGY 2011;53:448-457)

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