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Treatment of alpha-1 antitrypsin deficiency

James K Stoller, MD, MS
Section Editor
Peter J Barnes, DM, DSc, FRCP, FRS
Deputy Editor
Helen Hollingsworth, MD


Severe deficiency of alpha-1 antitrypsin (AAT) is associated with early onset pulmonary emphysema and with several forms of liver disease, including cirrhosis, neonatal hepatitis, and hepatocellular carcinoma.

The discovery of the structure and function of the AAT protein, and its subsequent isolation and purification, have allowed replacement therapy (so-called "augmentation therapy") aimed at preventing progression of the associated lung disease [1,2]. Isolation of the gene and advances in gene therapy have further broadened the potential for specific therapy. The goal of most specific treatment approaches for AAT deficiency is to raise the plasma AAT level (and therefore the concentration of AAT in the lung interstitium) above the protective threshold. Other experimental approaches seek to interfere with production of abnormal AAT protein or to prevent polymerization of abnormal AAT protein and encourage secretion from the hepatocyte. Organ transplantation is another option for patients with end-stage lung or liver disease.

The treatment of AAT deficiency will be reviewed here. The clinical manifestations, genetics, and diagnosis of AAT deficiency are discussed separately. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency" and "Extrapulmonary manifestations of alpha-1 antitrypsin deficiency".)


Intravenous augmentation via the infusion of pooled human alpha-1 proteinase inhibitor (alpha-1 antitrypsin, AAT) is currently the most direct and efficient means of elevating AAT levels in the plasma and in the lung interstitium [3,4].

Clinical efficacy — Limited data are available regarding the clinical efficacy of intravenous AAT. Infusion therapy appears to be safe, well tolerated, and without significant side effects [5-9]. To date, no randomized trial of adequate size has definitively demonstrated the clinical efficacy of augmentation therapy, though the authors believe that the weight of available evidence favors efficacy of augmentation therapy.


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Literature review current through: Sep 2016. | This topic last updated: Jul 19, 2016.
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