1. Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency
- Author
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Alice M Turner, David A. Lomas, Alexa Nuñez, Sabina Janciauskiene, William J.H. Griffiths, Christian Trautwein, Joan Genescà, Michael Trauner, John R. Hurst, Jef Verbeek, Matthias C. Reichert, Guilherme Macedo, Ravi Mahadeva, Mònica Pons, Aleksander Krag, Rui Gaspar, V Pereira, Heinz Zoller, Catarina Gomes, Mattias Mandorfer, Barbara Burbaum, Frank Lammert, V Woditsch, Paul Ellis, Aileen Marshall, Douglas Thorburn, Nadine T. Gaisa, Karim Hamesch, Joanna Chorostowska-Wynimko, Luís Jasmins, Malin Fromme, Rodrigo Liberal, Pavel Strnad, Frederik Nevens, Noel G. McElvaney, Marc Miravitlles, Virginia Clark, Bibek Gooptu, Benedikt Schaefer, Katrine Holtz Thorhauge, Carolin V. Schneider, Nelia Abreu, Kai Markus Schneider, Federica Benini, Fromme, Malin [0000-0003-0382-5705], Hamesch, Karim [0000-0002-1702-2746], Reichert, Matthias C [0000-0002-8192-0575], Mandorfer, Mattias [0000-0003-2330-0017], Gaspar, Rui [0000-0003-0332-3844], Trauner, Michael [0000-0002-1275-6425], Krag, Aleksander [0000-0002-9598-4932], Gooptu, Bibek [0000-0002-5223-1121], Hurst, John R [0000-0002-7246-6040], Lomas, David A [0000-0003-2339-6979], Strnad, Pavel [0000-0002-7122-6379], and Apollo - University of Cambridge Repository
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,liver cirrhosis ,liver ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Cholelithiasis ,Fibrosis ,alpha 1-Antitrypsin Deficiency ,Internal medicine ,Diabetes mellitus ,Genotype ,Prevalence ,medicine ,Humans ,cancer ,Aged ,Alpha 1-antitrypsin deficiency ,business.industry ,Liver Neoplasms ,fibrosis ,Cancer ,Gallstones ,Middle Aged ,medicine.disease ,United Kingdom ,Phenotype ,030228 respiratory system ,Case-Control Studies ,Female ,030211 gastroenterology & hepatology ,business - Abstract
ObjectiveAlpha-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.DesignBaseline 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.ResultsAmong 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.ConclusionOur 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.
- Published
- 2022
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