Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C.
OBJECTIVE
Recent evidence implicates iron as a comorbid factor for development of non-hemochromatotic liver diseases. Mutations or polymorphisms in the HFE gene or the TfR1 gene may influence the accumulation of iron in the liver or other tissues or may influence chronic viral hepatitis apart from effects on iron homeostasis. The aim of this study was to assess the role of hepatic iron, HFE and TfR1 variations on development and progression of chronic hepatitis C infection.


METHODS
We studied 119 consecutive patients with chronic hepatitis C, correlating clinical, laboratory, histopathological, and genetic data. Frequencies of genetic variations were compared with local and national controls.


RESULTS
HFE mutations were more common in patients than controls (48% vs. 38%, P=0.04), and advanced degrees of fibrosis developed at younger ages in subjects with the C282Y mutation (38.6 vs. 46.5 years, P=0.03). Patients carrying C282Y had higher mean hepatic iron concentrations (P=0.02), hepatic iron indices (P<=0.0001), and hepatic fibrosis scores (P=0.01). Hepatic fibrosis was correlated with hepatic iron concentration (P=0.03). TfR1 polymorphisms bore no detectable relation to disease severity or response to therapy.


CONCLUSIONS
Hepatic iron and HFE mutations are comorbid factors that increase development and progression of chronic hepatitis C.
Bonkovsky
Herbert L
HL
Liver-Biliary-Pancreatic Center, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Troy
Nicole
N
McNeal
Kristina
K
Banner
Barbara F
BF
Sharma
Ashish
A
Obando
Jorge
J
Mehta
Savant
S
Koff
Raymond S
RS
Liu
Qin
Q
Hsieh
Chung-Cheng
CC
D000328:Adult; D018450:Disease Progression; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D019698:Hepatitis C, Chronic / Q000209:etiology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011990:Receptors, Transferrin / Q000235:genetics*
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D007501:Iron