TY - JOUR
T1 - HFE mutations in α-1-antitrypsin deficiency
T2 - An examination of cirrhotic explants
AU - Lam, Maggie
AU - Torbenson, Michael
AU - Yeh, Matthew M.
AU - Vivekanandan, Perumal
AU - Ferrell, Linda
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - A-1-antitrypsin deficiency
KW - C282Y
KW - Cirrhosis
KW - H63D
KW - HFE mutation
KW - Hemochromatosis
UR - http://www.scopus.com/inward/record.url?scp=77952012348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952012348&partnerID=8YFLogxK
U2 - 10.1038/modpathol.2010.42
DO - 10.1038/modpathol.2010.42
M3 - Article
C2 - 20208481
AN - SCOPUS:77952012348
SN - 0893-3952
VL - 23
SP - 637
EP - 643
JO - Modern Pathology
JF - Modern Pathology
IS - 5
ER -