Insight Into Alpha-1 Antitrypsin Heterozygosity

CV Schneider, K Hamesch et al. Gastroenterol 2020; 159: 534-548Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers)

Key findings:

  • Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs (liver stiffness measurements) of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0–11.8)
  • Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype.
  • AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages.

The associated editorial (pg 433-34) noted that Pi∗MZ genotype is a disease modifier in cystic fibrosis, alcoholic liver disease, and nonalcoholic liver disease.

My take: This study indicates that Pi∗MZ genotype for alpha-one antitrypsin are more likely to develop liver fibrosis in the presence of other risk factors like obesity and diabetes mellitus.

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