Advances in Alpha-1-Antitrypsin Deficiency Liver Disease

Liver (B Bacon, Section Editor)

DOI: 10.1007/s11894-013-0367-8

Cite this article as:
Teckman, J.H. & Jain, A. Curr Gastroenterol Rep (2014) 16: 367. doi:10.1007/s11894-013-0367-8
  • 952 Downloads
Part of the following topical collections:
  1. Topical Collection on Liver

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.

Keywords

Alpha-1-antitrypsin Liver Apoptosis Hepatocellular proliferation Autophagy 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.St. Louis University School of Medicine, Cardinal Glennon Children’s Medical CenterSt. LouisUSA

Personalised recommendations