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Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C.

Abstract：

BACKGROUND & AIMS:Iron overload may cause or contribute to hepatic injury and fibrosis. Mutations in the HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on baseline features and response to lead-in therapy in subjects with advanced chronic hepatitis C enrolled in the Hepatitis C Anti-viral Long-term Treatment to prevent Cirrhosis (HALT-C) Trial. METHODS:Entry criteria included an Ishak fibrosis score >2 and lack of iron overload (Scheuer iron grade <3+) according to local study pathologists. All baseline biopsy specimens were rescored by consensus of study pathologists, and detailed assessment of stainable iron was performed. Hepatic iron concentrations were measured on portions of 144 liver biopsy specimens. A total of 1051 out of 1145 subjects agreed to HFE mutational testing (C282Y, H63D, S65C). RESULTS:Thirty-five percent carried at least one HFE gene mutation. There were no significant differences in the prevalence of HFE gene mutations among subjects with fibrosis (35.5%) versus cirrhosis (32.9%). Thirty-three percent of subjects had end-of-treatment and 16% sustained virologic responses. Presence of HFE mutations, in particular the H63D variation, was associated with increased end-of-treatment (40% vs 29%, P = .0078) and sustained virologic responses (20% with HFE mutation vs 14% sustained virologic response without HFE mutation; P = .009). CONCLUSIONS:Although HFE mutations (especially the most frequent H63D mutation) are associated with increased iron loading, they are also associated with increased sustained virologic responses in US patients with advanced chronic hepatitis C.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Bonkovsky HL,Naishadham D,Lambrecht RW,Chung RT,Hoefs JC,Nash SR,Rogers TE,Banner BF,Sterling RK,Donovan JA,Fontana RJ,Di Bisceglie AM,Ghany MG,Morishima C,HALT-C Trial Group.

doi

10.1053/j.gastro.2006.08.036

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1440-51

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(06)01796-3

journal_volume

131

pub_type

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Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C.