Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions.
OBJECTIVE
Liver iron accumulation has been described in patients with chronic active hepatitis (CAH) C, and could play a role in the course of liver disease and negatively influence the response to interferon. The aim of this study was to determine the prevalence and severity of liver iron accumulation in CAH C, to assess its relationship with the HFE C282Y and H63D mutations, and to study its interactions with hepatic histological lesions.


METHODS
Two hundred and nine patients (131 men, 78 women, mean age 44.3+/-12.0 years) with CAH C, including 19 patients with cirrhosis (9.1%) were studied. A semiquantitative grading system from 0 to 3 was used for histological assessment of liver iron accumulation on Perls' staining. The HFE C282Y and H63D mutations were screened for by restriction enzyme analysis performed on PCR-amplified products. Histological scores of activity and fibrosis were determined according to a previously validated METAVIR score system.


RESULTS
Liver iron accumulation was found in 88/209 patients (42.1%), and was generally mild. The C282Y and H63D allele frequencies were in 23 (11.0%), and 50 (23.9%), respectively. No association was found between the presence of liver iron accumulation and the detection of the C282Y and H63D mutations. A significant relationship was found between the severity of histological activity and liver iron accumulation of macrophagic or mixed (i.e. both macrophagic and hepatocytic) type (p = 0.04). Although the number of cirrhotic patients was small, cirrhosis was more frequently observed in patients with than without liver iron accumulation (17.2% vs. 3.3%, p = 0.004).


CONCLUSIONS
Overall, these data suggest that the liver iron accumulation in patients with CAH C is significantly associated with histological activity and cirrhosis, whereas the two missense hemochromatosis gene mutations are not major determinants.
Hézode
C
C
Department of Hepatology-Gastroenterology, Hôpital Henri Mondor, Université Paris XII, Créteil, France.
Cazeneuve
C
C
Coué
O
O
Roudot-Thoraval
F
F
Lonjon
I
I
Bastie
A
A
Duvoux
C
C
Pawlotsky
J M
JM
Zafrani
E S
ES
Amselem
S
S
Dhumeaux
D
D
D000328:Adult; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron