: 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.
Alpha-1 antitrypsin deficiency: a re-surfacing adult liver disorder / Fromme, Malin; Schneider, Carolin V; Trautwein, Christian; Brunetti-Pierri, Nicola; Strnad, Pavel. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - (2021). [10.1016/j.jhep.2021.11.022]
Alpha-1 antitrypsin deficiency: a re-surfacing adult liver disorder
Brunetti-Pierri, Nicola;
2021
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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.