Hfe mutations and iron overload in patients with alcoholic liver disease
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109706 https://doi.org/10.1590/s0004-28032013000100008 |
Resumo: | Context - Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives - To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods - Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results - ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions - ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity. |
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Hfe mutations and iron overload in patients with alcoholic liver diseaseAlcoholic liver diseaseMembrane proteinsIronHemochromatosisHepatopatias alcoólicasProteínas de membranaFerroHemocromatoseCase-Control StudiesFemaleGenotypeHemochromatosis ProteinHistocompatibility Antigens Class IHumansIron OverloadLiver Diseases, AlcoholicMaleMembrane ProteinsMiddle AgedSeverity of Illness IndexContext - Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives - To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods - Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results - ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions - ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity.Contexto - A doença hepática alcoólica (DHA) está geralmente associada à sobrecarga de ferro, que pode contribuir para a sua patogênese, através do aumento do estresse oxidativo e dano celular. As descrições existentes na literatura sobre a associação entre mutações HFE e a gravidade da DHA nem sempre são concordantes. Objetivos - Comparar a prevalência de mutações HFE entre um grupo de pacientes com DHA e uma população de controle. Avaliar a relação entre mutações HFE e os depósitos de ferro hepático. Avaliar se a presença dessas mutações está associada com a gravidade da DHA. Métodos – Compararam-se 63 pacientes com DHA que efetuaram biopsia hepática com 52 controles saudáveis. A genotipagem HFE (wild type, C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M, W164X) e uma avaliação laboratorial de rotina (incluindo cinética do ferro) foram feitos em todos os indivíduos. Realizou-se regressão logística multivariada nos casos para avaliar se a presença de mutações HFE estava relacionada com risco aumentado de depósitos de ferro hepático aumentados, ferritina sérica anormal, fibrose hepática significativa ou atividade necroinflamatória. Resultados - Os pacientes apresentaram ferritina sérica e saturação da transferrina mais elevadas que os controles, mas não existiram diferenças significativas na distribuição de mutações HFE entre pacientes e controles. Considerando apenas os pacientes, o risco relativo de estes apresentarem pelo menos uma mutação HFE e depósitos de ferro hepático significativos foi de 17.23 (CI 95% 2.09-142.34, P = 0.008). Contudo, a presença de pelo menos uma mutação HFE não esteve associada ao risco significativamente aumentado de fibrose ou atividade necroinflamatória significativas. O fator mais determinante para apresentar ferritina sérica acima do normal foi a presença de alcoolismo ativo, com risco relativo de 8.87 (CI 95% 2.11-34.78, P = 0.003). Conclusões - Não existiram diferenças na distribuição de mutações HFE entre pacientes com DHA e controles normais. Nos pacientes, o achado de pelo menos uma mutação HFE aumentou o risco de ter depósitos de ferro hepático mais elevados, mas não para ter fibrose ou atividade necroinflamatória significativas.Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109706http://hdl.handle.net/10316/109706https://doi.org/10.1590/s0004-28032013000100008engMatos, Luís CostaBatista, PauloMonteiro, NunoHenriques, PedroGirão, FernandoCarvalho, Armandoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-23T10:15:26Zoai:estudogeral.uc.pt:10316/109706Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:51.585163Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Hfe mutations and iron overload in patients with alcoholic liver disease |
title |
Hfe mutations and iron overload in patients with alcoholic liver disease |
spellingShingle |
Hfe mutations and iron overload in patients with alcoholic liver disease Matos, Luís Costa Alcoholic liver disease Membrane proteins Iron Hemochromatosis Hepatopatias alcoólicas Proteínas de membrana Ferro Hemocromatose Case-Control Studies Female Genotype Hemochromatosis Protein Histocompatibility Antigens Class I Humans Iron Overload Liver Diseases, Alcoholic Male Membrane Proteins Middle Aged Severity of Illness Index |
title_short |
Hfe mutations and iron overload in patients with alcoholic liver disease |
title_full |
Hfe mutations and iron overload in patients with alcoholic liver disease |
title_fullStr |
Hfe mutations and iron overload in patients with alcoholic liver disease |
title_full_unstemmed |
Hfe mutations and iron overload in patients with alcoholic liver disease |
title_sort |
Hfe mutations and iron overload in patients with alcoholic liver disease |
author |
Matos, Luís Costa |
author_facet |
Matos, Luís Costa Batista, Paulo Monteiro, Nuno Henriques, Pedro Girão, Fernando Carvalho, Armando |
author_role |
author |
author2 |
Batista, Paulo Monteiro, Nuno Henriques, Pedro Girão, Fernando Carvalho, Armando |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Matos, Luís Costa Batista, Paulo Monteiro, Nuno Henriques, Pedro Girão, Fernando Carvalho, Armando |
dc.subject.por.fl_str_mv |
Alcoholic liver disease Membrane proteins Iron Hemochromatosis Hepatopatias alcoólicas Proteínas de membrana Ferro Hemocromatose Case-Control Studies Female Genotype Hemochromatosis Protein Histocompatibility Antigens Class I Humans Iron Overload Liver Diseases, Alcoholic Male Membrane Proteins Middle Aged Severity of Illness Index |
topic |
Alcoholic liver disease Membrane proteins Iron Hemochromatosis Hepatopatias alcoólicas Proteínas de membrana Ferro Hemocromatose Case-Control Studies Female Genotype Hemochromatosis Protein Histocompatibility Antigens Class I Humans Iron Overload Liver Diseases, Alcoholic Male Membrane Proteins Middle Aged Severity of Illness Index |
description |
Context - Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives - To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods - Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results - ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions - ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/109706 http://hdl.handle.net/10316/109706 https://doi.org/10.1590/s0004-28032013000100008 |
url |
http://hdl.handle.net/10316/109706 https://doi.org/10.1590/s0004-28032013000100008 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia |
publisher.none.fl_str_mv |
Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134140245737472 |