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Publication Information
Affiliation
Virginia Mason Medical Center, Seattle, WA, USA.
Authors
Abdelmalek MF, Abrams SH, Ackermann S, Angeli L, Aouizerat B, Bambha K, Barlow S, Bass M, Bass NM, Behling C, Belt P, Boyett S, Brancati FL, Brandt P, Bringman D, Brunt EM, Buie S, Byam E, Chalasani N, Clark JM, Coffey M, Collins J, Colvin R, Contos MJ, Cosme Y, Cummings OW, Dasarathy J, Dasarathy S, Derdoy J, Devadason C, DeVore S, Diehl AM, Donithan M, Doo EC, Dunne K, Durelle J, Ferrell LD, Filipowski D, Fishbein MH, Fleck S, Fuchs M, Galdzicka S, Ghabril M, Gottfried M, Grave GD, Green M, Gu B, Guy C, Hameed B, Hanna M, Hassanein T, Hawkins C, Hollick R, Hoofnagle JH, Isaacson M, Jacques K, Jin WK, Jones A, Kerkar N, Kigongo C, Killenberg P, King D, Kleiner DE, Klipsch A, Kohli R, Kowdley KV, Kwan S, Lake K, Langlois C, Lavine JE, Liu YC, Loomba R, Luketic VA, Lydecker A, Mann P, May KP, McCullough AJ, Mencin A, Merriman R, Miriel L, Mohan P, Molleston JP, Mooney J, Morgan A, Morris A, Murray K, Nair K, Narayanappa S, Nelson J, Nelson JE, Neuschwander-Tetri BA, Nguyen A, Noble K, Nonalcoholic Steatohepatitis Clinical Research Network, Ovchinsky N, Pabst M, Pagadala M, Pan YP, Park J, Patton H, Pfeifer K, Pierce T, Piercy D, Puri P, Quinn A, Ragozzino L, Riazi C, Robuck PR, Rogers N, Rosenthal M, Rosenthal P, Rose S, Sandhu B, Sanyal AJ, Sargeant C, Sargent R, Scheimann A, Schwimmer JB, Shaw C, Sherker A, Siegner J, Sirlin C, Smith M, Srivastava S, Stager M, Stead A, Steel T, Stein T, Sternberg A, Stewart S, Subbarao G, Suchy F, Tandra S, Thompson J, Tonascia J, Torbenson M, Unalp-Arida A, Van Natta M, Vaughn I, Vuppalanchi R, Wang C, White M, Whitington PF, Whitwell J, Wilson L, Xanthakos S, Yates K, Yeh M, Yerian L, Zein C
Citation
Nelson JE, Brunt EM, Kowdley KV, Nonalcoholic Steatohepatitis Clinical Research Network. Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations. Hepatology 2012 Nov;56(5):1730-40. Epub 2012 Sep 20.Abstract
Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild-type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (odds ratio [OR], ≥1.4; 95% confidence interval [CI]: >1.0, ≤2.5; P ≤ 0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR, ≤0.62; 95% CI: >0.39, <0.94; P ≤ 0.024), compared to WT subjects.