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

被引:73
作者
Bonkovsky, Herbert L.
Naishadham, Deepa
Lambrecht, Richard W.
Chung, Raymond T.
Hoefs, John C.
Nash, S. Russell
Rogers, Thomas E.
Banner, Barbara F.
Sterling, Richard K.
Donovan, John A.
Fontana, Robert J.
Di Bisceglie, Adrian M.
Ghany, Marc G.
Morishima, Chihiro
机构
[1] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA
[2] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT 06030 USA
[3] Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06030 USA
[4] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT 06030 USA
[5] New England Res Inst, Watertown, MA 02172 USA
[6] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA
[7] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA
[8] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA
[9] Univ Colorado, Dept Pathol, Denver, CO 80202 USA
[10] Hlth Sci Ctr, Denver, CO 80202 USA
[11] Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75216 USA
[12] Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA
[13] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA
[14] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA
[15] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA
[16] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA
[17] NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[18] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA
关键词
D O I
10.1053/j.gastro.2006.08.036
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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收藏
页码:1440 / 1451
页数:12
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