HFE mutations in α-1-antitrypsin deficiency: An examination of cirrhotic explants

Maggie Lam, Michael Torbenson, Matthew M. Yeh, Perumal Vivekanandan, Linda Ferrell

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Increased iron deposition is often seen in liver explants with α-1-antitrypsin deficiency, but it remains unclear if this is a nonspecific effect of end-stage liver disease or if individuals with α-1-antitrypsin deficiency and excess iron are at increased risk for HFE mutations. To further examine this question, 45 liver explants with α-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 α-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 α-1-antitrypsin deficiency were as follows: C282Y2%, H63D42%. H63D mutations were more frequent in α-1-antitrypsin deficiency cases than in controls (42 vs 27%), but was not statistically significant, P0.17. However, there was a significant association with HFE mutations in α-1-antitrypsin deficiency livers with grade 3 or 4 iron, P0.02. In contrast, livers with hepatitis C showed a similar frequency of HFE mutations as the general population: C282Y15%, H63D27%. 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 α-1-antitrypsin deficiency and there was a significant association between HFE mutations and high levels of iron accumulation.

Original languageEnglish (US)
Pages (from-to)637-643
Number of pages7
JournalModern Pathology
Issue number5
StatePublished - May 2010


  • A-1-antitrypsin deficiency
  • C282Y
  • Cirrhosis
  • H63D
  • HFE mutation
  • Hemochromatosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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