There is no cure for the disease but many individuals, especially non-smokers, have normal lifespans.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
[58]Seersholm N, Kok-Jensen A, Dirksen A. Survival of patients with severe alpha-1 antitrypsin deficiency with special reference to non-index cases. Thorax. 1994;49:695-698.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC475060/pdf/thorax00299-0073.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8066566?tool=bestpractice.com
Lung disease
Between 50% and 72% of deaths in AAT deficiency are caused by respiratory failure, which comprises a greater percentage of deaths than liver failure.[24]Larsson C. Natural history and life expectancy in severe alpha 1-antitrypsin deficiency, Pi Z. Acta Med Scand. 1978;204:345-351.
http://www.ncbi.nlm.nih.gov/pubmed/309708?tool=bestpractice.com
[63]Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha 1-antitrypsin. Am J Respir Crit Care Med. 1998;158:49-59.
http://www.ncbi.nlm.nih.gov/pubmed/9655706?tool=bestpractice.com
[99]Dawkins PA, Dowson LJ, Guest PJ, et al. Predictors of mortality in alpha 1-antitrypsin deficiency. Thorax. 2003;58:1020-1026.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746543/pdf/v058p01020.pdf
http://www.ncbi.nlm.nih.gov/pubmed/14645964?tool=bestpractice.com
Evidence suggests the median age of death in AAT deficiency is 40 years in smokers and 65 years in non-smokers, owing to early-onset emphysema and progressive lung disease.[24]Larsson C. Natural history and life expectancy in severe alpha 1-antitrypsin deficiency, Pi Z. Acta Med Scand. 1978;204:345-351.
http://www.ncbi.nlm.nih.gov/pubmed/309708?tool=bestpractice.com
FEV1 should be used as a predictor of survival in these patients, as correlation has been established between 2-year mortality and FEV1 >35%.[100]Seersholm N, Dirksen A, Kok-Jensen A. Airways obstruction and two-year survival in patients with severe alpha-1 antitrypsin deficiency. Eur Respir J. 1994;7:1985-1987.
http://www.ncbi.nlm.nih.gov/pubmed/7875269?tool=bestpractice.com
Rates of decline of FEV1 range from 47 to 80 mL/year in people who have never smoked, 41 to 81 mL/year in ex-smokers, and 61 to 316 mL/year in smokers.[46]Janus ED, Phillips NT, Carrell RW. Smoking, lung function, and alpha-1-antitrypsin deficiency. Lancet. 1985;1:152-4.
http://www.ncbi.nlm.nih.gov/pubmed/2857224?tool=bestpractice.com
[47]Wu MC, Eriksson S. Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ. J Clin Epidemiol. 1988;41:1157-1165.
http://www.ncbi.nlm.nih.gov/pubmed/3264848?tool=bestpractice.com
[48]Piitulainen E, Eriksson S. Decline in FEV1 related to smoking status in individuals with severe alpha-1 antitrypsin deficiency (PiZZ). Eur Respir J. 1999;13:247-251.
http://erj.ersjournals.com/cgi/reprint/13/2/247
http://www.ncbi.nlm.nih.gov/pubmed/10065663?tool=bestpractice.com
AAT augmentation therapy is effective in slowing radiographical evidence of lung disease, and also in providing mortality benefit.[62]Dirksen A, Dijkman JH, Madsen F, et al. A randomized clinical trial of alpha 1-antitrypsin augmentation therapy. Am J Respir Crit Care Med. 1999;160:1468-1472.
http://www.ncbi.nlm.nih.gov/pubmed/10556107?tool=bestpractice.com
[63]Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha 1-antitrypsin. Am J Respir Crit Care Med. 1998;158:49-59.
http://www.ncbi.nlm.nih.gov/pubmed/9655706?tool=bestpractice.com
The 5-year survival rate following lung transplant is approximately 50%.[81]Hosenpud JD, Novick RJ, Breen TJ, et al. The registry of the International Society for Heart and Lung Transplanation: twelfth official report. J Heart Lung Transplant. 1995;14:805-815.
http://www.ncbi.nlm.nih.gov/pubmed/8800714?tool=bestpractice.com
[82]Levine SM, Anzueto A, Peters JI, et al. Medium term functional results of single-lung transplantation for end stage obstructive lung disease. Am J Respir Crit Care Med. 1994;150:398-402.
http://www.ncbi.nlm.nih.gov/pubmed/8049821?tool=bestpractice.com
[83]Christie JD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult lung and heart-lung transplant report - 2011. J Heart Lung Transplant. 2011;30:1104-1122.
http://www.jhltonline.org/article/S1053-2498%2811%2901089-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21962018?tool=bestpractice.com
Median survival is 6.3 years.[83]Christie JD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult lung and heart-lung transplant report - 2011. J Heart Lung Transplant. 2011;30:1104-1122.
http://www.jhltonline.org/article/S1053-2498%2811%2901089-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21962018?tool=bestpractice.com
Liver disease
Patients who are PI*ZZ and do not manifest pulmonary symptoms are more likely to experience cirrhosis and ultimately liver failure.[27]Eriksson S. Alpha 1-antitrypsin deficiency: natural course and therapeutic strategies. In: Boyer J, Blum HE, Maier KP, et al, eds. Cirrhosis and its development. Falk Symposium 115. Dordrecht, Netherlands: Kluwer Academic; 2000:307-315.
Liver fibrosis has been detected in 20% to 36% of asymptomatic adults with PI*ZZ AAT deficiency, while the reported prevalence of cirrhosis ranges from 2% to 43%.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
[28]Hamesch K, Mandorfer M, Pereira VM, et al. Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology. 2019 Sep;157(3):705-719.e18.
https://www.doi.org/10.1053/j.gastro.2019.05.013
http://www.ncbi.nlm.nih.gov/pubmed/31121167?tool=bestpractice.com
[29]Clark VC, Marek G, Liu C, et al. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol. 2018 Dec;69(6):1357-1364.
https://www.doi.org/10.1016/j.jhep.2018.08.005
http://www.ncbi.nlm.nih.gov/pubmed/30138687?tool=bestpractice.com
The prevalence of cirrhosis is higher in older PI*ZZ adults who have never smoked; one third of patients with advanced age and a homozygous phenotype will die of complications related to portal hypertension and primary liver cancer.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com