Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • معلومة اضافية
    • الموضوع:
      2021
    • Collection:
      University College London: UCL Discovery
    • نبذة مختصرة :
      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.
    • File Description:
      text
    • Relation:
      https://discovery.ucl.ac.uk/id/eprint/10123513/11/Lomas_Manuscript_SZ_210102_Gut.pdf; https://discovery.ucl.ac.uk/id/eprint/10123513/5/Lomas_Supplement_SZ_210101_Gut_CS.pdf; https://discovery.ucl.ac.uk/id/eprint/10123513/
    • الدخول الالكتروني :
      https://discovery.ucl.ac.uk/id/eprint/10123513/11/Lomas_Manuscript_SZ_210102_Gut.pdf
      https://discovery.ucl.ac.uk/id/eprint/10123513/5/Lomas_Supplement_SZ_210101_Gut_CS.pdf
      https://discovery.ucl.ac.uk/id/eprint/10123513/
    • Rights:
      open
    • الرقم المعرف:
      edsbas.7B2D3A90