Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder

J Hepatol. 2022 Apr;76(4):946-958. doi: 10.1016/j.jhep.2021.11.022. Epub 2021 Nov 27.


Alpha-1 antitrypsin deficiency (AATD) arises from mutations in the SERPINA1 gene encoding alpha-1 antitrypsin (AAT) that lead to AAT retention in the endoplasmic reticulum of hepatocytes, causing proteotoxic liver injury and loss-of-function lung disease. The homozygous Pi∗Z mutation (Pi∗ZZ genotype) is responsible for the majority of severe AATD cases and can precipitate both paediatric and adult liver diseases, while the heterozygous Pi∗Z mutation (Pi∗MZ genotype) is an established genetic modifier of liver disease. We review genotype-related hepatic phenotypes/disease predispositions. We also describe the mechanisms and factors promoting the development of liver disease, as well as approaches to evaluate the extent of liver fibrosis. Finally, we discuss emerging diagnostic and therapeutic approaches for the clinical management of this often neglected disorder.

Keywords: Fibroscan; Pi∗S; Pi∗Z; SERPINA1; liver cirrhosis; liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Child
  • Heterozygote
  • Homozygote
  • Humans
  • Liver Cirrhosis* / diagnosis
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin Deficiency* / complications
  • alpha 1-Antitrypsin Deficiency* / diagnosis
  • alpha 1-Antitrypsin Deficiency* / genetics


  • alpha 1-Antitrypsin