Alpha-1-Antitrypsin Deficiency Liver Disease.

Dhiren Patel, Jeffrey H Teckman

Journal: Clinics in liver disease 2019;22(4):643-655

PMID: 30266154

Full Text on Elsevier Science View on PubMed

Abstract

In homozygous ZZ alpha-1-antitrypsin (AAT) deficiency, the liver synthesizes large quantities of AAT mutant Z, which folds improperly during biogenesis and is retained within the hepatocytes and directed into intracellular proteolysis pathways. These intracellular polymers trigger an injury cascade, which can lead to liver injury. This is highly variable and not all patients develop liver disease. Although not fully described, there is likely a strong influence of genetic and environmental modifiers of the injury cascade and of the fibrotic response. With improved understanding of liver injury mechanisms, new strategies for treatment are now being explored.

Address: Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA.; Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA; Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, USA. Electronic address: [email protected].

DOI: 10.1016/j.cld.2018.06.010