| Title: | Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency |
| Journal: | Gut |
| Published: | 25 Feb 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33632708/ |
| DOI: | https://doi.org/10.1136/gutjnl-2020-323729 |
| URL: | https://birmingham.elsevierpure.com/files/113701909/Revised_Manuscript_Supplement_SZ_210105_Gut.pdf |
Publication 5127
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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.</p>
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.</p>
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.</p>
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.</p>
15 Keywords
- Adult
- Aged
- Case-Control Studies
- Cholelithiasis
- Cohort Studies
- Female
- Humans
- Liver Cirrhosis
- Liver Neoplasms
- Male
- Middle Aged
- Phenotype
- Prevalence
- United Kingdom
- alpha 1-Antitrypsin Deficiency
44 Authors
- Malin Fromme
- Carolin V Schneider
- Vitor Pereira
- Karim Hamesch
- Monica Pons
- Matthias C Reichert
- Federica Benini
- Paul Ellis
- Katrine H Thorhauge
- Mattias Mandorfer
- Barbara Burbaum
- Vivien Woditsch
- Joanna Chorostowska-Wynimko
- Jef Verbeek
- Frederik Nevens
- Joan Genesca
- Marc Miravitlles
- Alexa Nuñez
- Benedikt Schaefer
- Heinz Zoller
- Sabina Janciauskiene
- Nélia Abreu
- Luís Jasmins
- Rui Gaspar
- Rodrigo Liberal
- Guilherme Macedo
- Ravi Mahadeva
- Catarina Gomes
- Kai Markus Schneider
- Michael Trauner
- Aleksander Krag
- Bibek Gooptu
- Douglas Thorburn
- Aileen Marshall
- John R Hurst
- David A Lomas
- Frank Lammert
- Nadine T Gaisa
- Virginia Clark
- William Griffiths
- Christian Trautwein
- Alice M Turner
- Noel G McElvaney
- Pavel Strnad
Enabling scientific discoveries that improve human health