TY - JOUR T1 - Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency JF - Gut JO - Gut SP - 415 LP - 423 DO - 10.1136/gutjnl-2020-323729 VL - 71 IS - 2 AU - Malin Fromme AU - Carolin V Schneider AU - Vitor Pereira AU - Karim Hamesch AU - Monica Pons AU - Matthias C Reichert AU - Federica Benini AU - Paul Ellis AU - Katrine H Thorhauge AU - Mattias Mandorfer AU - Barbara Burbaum AU - Vivien Woditsch AU - Joanna Chorostowska-Wynimko AU - Jef Verbeek AU - Frederik Nevens AU - Joan Genesca AU - Marc Miravitlles AU - Alexa Nuñez AU - Benedikt Schaefer AU - Heinz Zoller AU - Sabina Janciauskiene AU - Nélia Abreu AU - Luís Jasmins AU - Rui Gaspar AU - Rodrigo Liberal AU - Guilherme Macedo AU - Ravi Mahadeva AU - Catarina Gomes AU - Kai Markus Schneider AU - Michael Trauner AU - Aleksander Krag AU - Bibek Gooptu AU - Douglas Thorburn AU - Aileen Marshall AU - John R Hurst AU - David A Lomas AU - Frank Lammert AU - Nadine T Gaisa AU - Virginia Clark AU - William Griffiths AU - Christian Trautwein AU - Alice M Turner AU - Noel G McElvaney AU - Pavel Strnad Y1 - 2022/02/01 UR - http://gut.bmj.com/content/71/2/415.abstract N2 - 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.Data are available upon reasonable request. The deidentified participant data are available from the corresponding author upon request. ER -