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

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

Malin Fromme  1 , Carolin V Schneider  1 , Christian Trautwein  1 , Nicola Brunetti-Pierri  2 , Pavel Strnad  3
Affiliations
Review

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

Malin Fromme et al. J Hepatol. 2022 Apr.

Abstract

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.

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Conflict of interest statement

Conflict of interest All authors declare no support from any organization other than the abovementioned organizations for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 5 years, and no other associations or activities that could appear to have influenced the submitted work. Hence, all authors declare themselves independent of funders concerning this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details.

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