Advances in alpha-1-antitrypsin deficiency liver disease.

Abstract

Alpha-1-antitrypsin (a1AT) deficiency is a common, but under-diagnosed, genetic disease. In the classical form, patients are homozygous for the Z mutant of the a1AT gene (called ZZ or PIZZ), which occurs in 1 in 2,000-3,500 births. The mutant Z gene directs the synthesis of large quantities of the mutant Z protein in the liver, which folds abnormally during biogenesis and accumulates intracellularly, rather than being efficiently secreted. The accumulation mutant Z protein within hepatocytes causes liver injury, cirrhosis, and hepatocellular carcinoma via a cascade of chronic hepatocellular apoptosis, regeneration, and end organ injury. There is no specific treatment for a1AT-associated liver disease, other than standard supportive care and transplantation. There is high variability in the clinical manifestations among ZZ homozygous patients, suggesting a strong influence of genetic and environmental modifiers. New insights into the biological mechanisms of intracellular injury have led to new, rational therapeutic approaches.

• Authors: Jeffrey H Teckman, Ajay Jain
• Journal: Current gastroenterology reports (Curr Gastroenterol Rep) Vol. 16 Issue 1 Pg. 367 (Jan 2014) ISSN: 1534-312X [Electronic] United States
• PMID: 24338605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• alpha 1-Antitrypsin

Topics

• Apoptosis (genetics)
• Hepatocytes (pathology)
• Heterozygote
• Homozygote
• Humans
• Liver Diseases (diagnosis, genetics, therapy)
• Mutation
• alpha 1-Antitrypsin (genetics)
• alpha 1-Antitrypsin Deficiency (diagnosis, genetics, therapy)