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Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency.
Fromme, Malin; Schneider, Carolin V; Pereira, Vitor; Hamesch, Karim; Pons, Monica; Reichert, Matthias C; Benini, Federica; Ellis, Paul; H Thorhauge, Katrine; Mandorfer, Mattias; Burbaum, Barbara; Woditsch, Vivien; Chorostowska-Wynimko, Joanna; Verbeek, Jef; Nevens, Frederik; Genesca, Joan; Miravitlles, Marc; Nuñez, Alexa; Schaefer, Benedikt; Zoller, Heinz; Janciauskiene, Sabina; Abreu, Nélia; Jasmins, Luís; Gaspar, Rui; Liberal, Rodrigo; Macedo, Guilherme; Mahadeva, Ravi; Gomes, Catarina; Schneider, Kai Markus; Trauner, Michael; Krag, Aleksander; Gooptu, Bibek; Thorburn, Douglas; Marshall, Aileen; Hurst, John R; Lomas, David A; Lammert, Frank; Gaisa, Nadine T; Clark, Virginia; Griffiths, William; Trautwein, Christian; Turner, Alice M; McElvaney, Noel G; Strnad, Pavel.
Afiliación
  • Fromme M; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Schneider CV; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Pereira V; Department of Gastroenterology, Centro Hospitalar do Funchal, Madeira, Portugal.
  • Hamesch K; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Pons M; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Barcelona, Catalunya, Spain.
  • Reichert MC; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Comunidad de Madrid, Spain.
  • Benini F; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
  • Ellis P; Gastroenterology Unit, Department of Medicine, Spedali Civili and University, Brescia, Italy.
  • H Thorhauge K; Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
  • Mandorfer M; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
  • Burbaum B; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria.
  • Woditsch V; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Chorostowska-Wynimko J; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Verbeek J; Department of Genetics and Clinical Immunology, National Tuberculosis and Lung Diseases Institute, Warszawa, Poland.
  • Nevens F; Department of Gastroenterology & Hepatology, KU Leuven University Hospitals Leuven, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Leuven, Flanders, Belgium.
  • Genesca J; Department of Gastroenterology & Hepatology, KU Leuven University Hospitals Leuven, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Leuven, Flanders, Belgium.
  • Miravitlles M; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Barcelona, Catalunya, Spain.
  • Nuñez A; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Comunidad de Madrid, Spain.
  • Schaefer B; Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
  • Zoller H; Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
  • Janciauskiene S; Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Tirol, Austria.
  • Abreu N; Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Tirol, Austria.
  • Jasmins L; Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
  • Gaspar R; Department of Gastroenterology, Centro Hospitalar do Funchal, Madeira, Portugal.
  • Liberal R; Department of Gastroenterology, Centro Hospitalar do Funchal, Madeira, Portugal.
  • Macedo G; Gastroenterology Department, Centro Hospitalar de São João, Faculty of Medicine of Porto University, Porto, Portugal.
  • Mahadeva R; Gastroenterology Department, Centro Hospitalar de São João, Faculty of Medicine of Porto University, Porto, Portugal.
  • Gomes C; Gastroenterology Department, Centro Hospitalar de São João, Faculty of Medicine of Porto University, Porto, Portugal.
  • Schneider KM; Department of Respiratory Medicine, Cambridge University Hospitals, Cambridge, UK.
  • Trauner M; Gastroenterology Department, Centro Hospitalar de Vila Nova de Gaia Espinho EPE, Vila Nova de Gaia, Porto, Portugal.
  • Krag A; Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
  • Gooptu B; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria.
  • Thorburn D; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
  • Marshall A; NIHR Leicester BRC-Respiratory and Leicester Institute of Structural & Chemical Biology, University of Leicester, Leicester, Leicestershire, UK.
  • Hurst JR; London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, UK.
  • Lomas DA; London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, UK.
  • Lammert F; Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
  • Gaisa NT; London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, UK.
  • Clark V; Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
  • Griffiths W; London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, UK.
  • Trautwein C; UCL Respiratory, Division of Medicine, University College London, London, UK.
  • Turner AM; London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, UK.
  • McElvaney NG; UCL Respiratory, Division of Medicine, University College London, London, UK.
  • Strnad P; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Gut ; 71(2): 415-423, 2022 02.
Article en En | MEDLINE | ID: mdl-33632708
ABSTRACT

OBJECTIVE:

Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.

DESIGN:

Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.

RESULTS:

Among UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.

CONCLUSION:

Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Colelitiasis / Deficiencia de alfa 1-Antitripsina / Cirrosis Hepática / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Gut Año: 2022 Tipo del documento: Article País de afiliación: Alemania
Texto completo
Imprimir
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Colelitiasis / Deficiencia de alfa 1-Antitripsina / Cirrosis Hepática / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Gut Año: 2022 Tipo del documento: Article País de afiliación: Alemania