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

: 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 pediatric and adult liver diseases, while the heterozygous Pi*Z mutation (Pi*MZ genotype) is an established 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. We discuss the emerging therapeutic approaches, diagnosis, and clinical management of this neglected disorder