Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease

Kris V. Kowdley, Patricia Belt, Laura A. Wilson, Matthew M. Yeh, Brent A. Neuschwander-Tetri, Naga Chalasani, Arun J. Sanyal, James E. Nelson

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalHepatology
Volume55
Issue number1
DOIs
StatePublished - Jan 2012

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Ferritins
Fibrosis
Iron
Serum
Liver
Odds Ratio
Confidence Intervals
Biopsy
Non-alcoholic Fatty Liver Disease
Transferrin
Aspartate Aminotransferases
Alanine Transaminase
Coloring Agents
Blood Platelets
Demography
Inflammation

ASJC Scopus subject areas

  • Hepatology

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Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. / Kowdley, Kris V.; Belt, Patricia; Wilson, Laura A.; Yeh, Matthew M.; Neuschwander-Tetri, Brent A.; Chalasani, Naga; Sanyal, Arun J.; Nelson, James E.

In: Hepatology, Vol. 55, No. 1, 01.2012, p. 77-85.

Research output: Contribution to journalArticle

Kowdley, KV, Belt, P, Wilson, LA, Yeh, MM, Neuschwander-Tetri, BA, Chalasani, N, Sanyal, AJ & Nelson, JE 2012, 'Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease', Hepatology, vol. 55, no. 1, pp. 77-85. https://doi.org/10.1002/hep.24706
Kowdley, Kris V. ; Belt, Patricia ; Wilson, Laura A. ; Yeh, Matthew M. ; Neuschwander-Tetri, Brent A. ; Chalasani, Naga ; Sanyal, Arun J. ; Nelson, James E. / Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. In: Hepatology. 2012 ; Vol. 55, No. 1. pp. 77-85.
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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.",
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T1 - Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease

AU - Kowdley, Kris V.

AU - Belt, Patricia

AU - Wilson, Laura A.

AU - Yeh, Matthew M.

AU - Neuschwander-Tetri, Brent A.

AU - Chalasani, Naga

AU - Sanyal, Arun J.

AU - Nelson, James E.

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N2 - 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.

AB - 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.

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