PubMed ID:
22611049
Public Release Type:
Journal
Publication Year: 2012
Affiliation: Virginia Mason Medical Center, Seattle, WA, USA.
DOI:
https://doi.org/10.1002/hep.25856
Authors:
Hoofnagle JH,
Vuppalanchi R,
Kleiner DE,
Nguyen A,
Chalasani N,
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,
Brunt EM,
Buie S,
Byam E,
Clark JM,
Coffey M,
Collins J,
Colvin R,
Contos MJ,
Cosme Y,
Cummings OW,
Dasarathy J,
Dasarathy S,
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,
Isaacson M,
Jacques K,
Jin WK,
Jones A,
Kerkar N,
Kigongo C,
Killenberg P,
King D,
Klipsch A,
Kohli R,
Kowdley KV,
Kowdley KV,
Kwan S,
Lake K,
Langlois C,
Lavine JE,
Lavine JE,
Liu YC,
Loomba R,
Luketic VA,
Lydecker A,
Mann P,
May KP,
McCullough AJ,
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,
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,
Wang C,
White M,
Whitington PF,
Whitwell J,
Wilson L,
Xanthakos S,
Yates K,
Yeh M,
Yerian L,
Zein C
Studies:
Nonalcoholic Steatohepatitis Clinical Research Network
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.