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Advances in Alpha-1-Antitrypsin Deficiency Liver Disease

  • Liver (B Bacon, Section Editor)
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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.

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Conflict of Interest

Dr. Teckman declares board membership on the Alpha-1 Foundation, The Alpha-1 Project, and the Alpha-1 Association. He is a consultant and received a research grant from Alnylam Pharmaceuticals; a consultant and research collaborator for Isis Pharmaceuticals; a consultant for and has a research contract with Arrowhead Research; and a consultant for Agios Inc. He has received grants from Alpha-1 Foundation and the NIH, and travel accommodations from Alpha-1 Foundation and Alpha-1 Association. Dr. Jain has no conflicts of interest.

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  1. St. Louis University School of Medicine, Cardinal Glennon Children’s Medical Center, 1465 South Grand Blvd., St. Louis, MO, 63104, USA

    Jeffrey H. Teckman & Ajay Jain

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  1. Jeffrey H. Teckman
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Correspondence to Jeffrey H. Teckman.

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Teckman, J.H., Jain, A. Advances in Alpha-1-Antitrypsin Deficiency Liver Disease. Curr Gastroenterol Rep 16, 367 (2014). https://doi.org/10.1007/s11894-013-0367-8

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