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- Title
HFE mutations in alpha-1-antitrypsin deficiency: an examination of cirrhotic explants.
- Authors
Lam, Maggie; Torbenson, Michael; Yeh, Matthew M; Vivekanandan, Perumal; Ferrell, Linda
- Abstract
Increased iron deposition is often seen in liver explants with alpha-1-antitrypsin deficiency, but it remains unclear if this is a nonspecific effect of end-stage liver disease or if individuals with alpha-1-antitrypsin deficiency and excess iron are at increased risk for HFE mutations. To further examine this question, 45 liver explants with alpha-1-antitrypsin deficiency and 33 control livers with chronic hepatitis C were examined for histological iron accumulation, graded on a scale of 0 to 4+, and HFE mutations. Interestingly, the alpha-1-antitrypsin cirrhotic livers showed a bimodal distribution of iron accumulation, with peaks at grades 1 and 3. In contrast, hepatitis C cirrhotic livers showed a unimodal distribution with a peak at grade 2. HFE mutations in livers with alpha-1-antitrypsin deficiency were as follows: C282Y=2%, H63D=42%. H63D mutations were more frequent in alpha-1-antitrypsin deficiency cases than in controls (42 vs 27%), but was not statistically significant, P=0.17. However, there was a significant association with HFE mutations in alpha-1-antitrypsin deficiency livers with grade 3+ or 4+ iron, P=0.02. In contrast, livers with hepatitis C showed a similar frequency of HFE mutations as the general population: C282Y=15%, H63D=27%. A rare S65C mutation and a novel A271S mutation were also found in this study; the latter patient had 4+ iron in the liver and later developed heart failure with cardiac iron. In conclusion, total H63D mutations were high (42%) in cirrhotics with alpha-1-antitrypsin deficiency and there was a significant association between HFE mutations and high levels of iron accumulation.
- Publication
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2010, Vol 23, Issue 5, p637
- ISSN
1530-0285
- Publication type
Journal Article
- DOI
10.1038/modpathol.2010.42