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Current Pediatric Reviews

Editor-in-Chief

ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Systematic Review Article

Alpha1-Antitrypsin Deficiency: Transition of Care for the Child With AAT Deficiency into Adulthood

Author(s): Henry C. Lin, Nagraj Kasi and J. Antonio Quiros*

Volume 15, Issue 1, 2019

Page: [53 - 61] Pages: 9

DOI: 10.2174/1573396314666181113094517

Abstract

Importance: Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children.

Objective: To review the literature on the management of AAT deficiency-associated liver disease in adults and children.

Evidence Review: A systematic search for articles indexed in PubMed and published was undertaken. Some earlier selected landmark references were included in the review. Search terms included: “alpha1-antitrypsin deficiency”; “liver disease”; “end-stage liver disease”; “liver transplantation” and “preventative management”. Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale.

Findings: Liver complications arising from AAT deficiency result from the accumulation of mutated AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis, pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver function tests should be obtained to assess for liver involvement; however, the only curative treatment for AAT deficiency-associated liver disease is organ transplantation.

Conclusion and Relevance: There should be a greater vigilance for AAT deficiency testing among pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency- associated liver disease should be referred to a liver specialist and monitored throughout their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement.

Keywords: Alpha1-antitrypsin deficiency, systematic review, pediatric liver disease, diagnosis, emphysema, pulmonary function tests.

Graphical Abstract
[1]
Laurell CB, Eriksson S. The electrophoretic a-1-globulin pattern of serum in a-1-antitrypsin deficiency. Scand J Clin Lab Invest 1963; 15(2): 132-40.
[2]
Sveger T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med 1976; 294(24): 1316-21.
[3]
Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest 2005; 128(3): 1179-86.
[4]
Lara B. COPD and alpha-1-antitrypsin deficiency. Arch Bronconeumol 2010; 46(Suppl. 4): 2-8.
[5]
Rahaghi FF, Sandhaus RA, Strange C, et al. The prevalence of alpha-1 antitrypsin deficiency among patients found to have airflow obstruction. COPD 2012; 9(4): 352-8.
[6]
Sharp HL, Bridges RA, Krivit W, Freier EF. Cirrhosis associated with alpha-1-antitrypsin deficiency: A previously unrecognized inherited disorder. J Lab Clin Med 1969; 73(6): 934-9.
[7]
Sharp HL. History of the first description of childhood liver disease in AATD. COPD 2013; 10(Suppl. 1): 13-6.
[8]
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; 168(7): 818-900.
[9]
McLean C, Greene CM, McElvaney NG. Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency. Biologics 2009; 3: 63-75.
[10]
Fairbanks KD, Tavill AS. Liver disease in alpha 1-antitrypsin deficiency: A review. Am J Gastroenterol 2008; 103(8): 2136-41.
[11]
Stoller JK, Aboussouan LS. A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2012; 185(3): 246-59.
[12]
Fregonese L, Stolk J, Frants RR, Veldhuisen B. Alpha-1 antitrypsin Null mutations and severity of emphysema. Respir Med 2008; 102(6): 876-84.
[13]
Molloy K, Hersh CP, Morris VB, et al. Clarification of the risk of chronic obstructive pulmonary disease in alpha1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med 2014; 189(4): 419-27.
[14]
Lomas DA. Twenty years of polymers: A personal perspective on alpha-1 antitrypsin deficiency. COPD 2013; 10(Suppl. 1): 17-25.
[15]
Teckman JH. Liver disease in alpha-1 antitrypsin deficiency: Current understanding and future therapy. COPD 2013; 10(Suppl. 1): 35-43.
[16]
Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992; 357(6379): 605-7.
[17]
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009; 6(7): e1000097.
[18]
Ebell MH, Siwek J, Weiss BD, et al. Strength Of Recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature. J Am Board Fam Pract 2004; 17(1): 59-67.
[19]
Moyer V, Freese DK, Whitington PF, et al. Guideline for the evaluation of cholestatic jaundice in infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39(2): 115-28.
[20]
Francavilla R, Castellaneta SP, Hadzic N, et al. Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. J Hepatol 2000; 32(6): 986-92.
[21]
Kalsheker NA. alpha1-Antitrypsin deficiency: Best clinical practice. J Clin Pathol 2009; 62(10): 865-9.
[22]
Sveger T, Eriksson S. The liver in adolescents with alpha 1-antitrypsin deficiency. Hepatology 1995; 22(2): 514-7.
[23]
Dawwas MF, Davies SE, Griffiths WJ, Lomas DA, Alexander GJ. Prevalence and risk factors for liver involvement in individuals with PiZZ-related lung disease. Am J Respir Crit Care Med 2013; 187(5): 502-8.
[24]
Clark VC, Dhanasekaran R, Brantly M, Rouhani F, Schreck P, Nelson DR. Liver test results do not identify liver disease in adults with alpha(1)-antitrypsin deficiency. Clin Gastroenterol Hepatol 2012; 10(11): 1278-83.
[25]
Rudnick DA, Perlmutter DH. Alpha-1-antitrypsin deficiency: A new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005; 42(3): 514-21.
[26]
Rakela J, Goldschmiedt M, Ludwig J. Late manifestation of chronic liver disease in adults with alpha-1-antitrypsin deficiency. Dig Dis Sci 1987; 32(12): 1358-62.
[27]
De Tommaso AM, Rossi CL, Escanhoela CA, et al. Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease. Arq Gastroenterol 2001; 38(1): 63-8.
[28]
Filipponi F, Soubrane O, Labrousse F, et al. Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: Pretransplant natural history, timing and results of transplantation. J Hepatol 1994; 20(1): 72-8.
[29]
Rashid ST, Corbineau S, Hannan N, et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 2010; 120(9): 3127-36.
[30]
Kemmer N, Kaiser T, Zacharias V, Neff GW. Alpha-1-antitrypsin deficiency: Outcomes after liver transplantation. Transplant Proc 2008; 40(5): 1492-4.
[31]
Bakula A, Socha P, Pawlowska J, Teisseyre M, Jankowska I, Kalicinski P. Good and bad prognosis of alpha-1-antitrypsin deficiency in children: When to list for liver transplantation. Transplant Proc 2007; 39(10): 3186-8.
[32]
Hughes MG Jr, Khan KM, Gruessner AC, et al. Long-term outcome in 42 pediatric liver transplant patients with alpha 1-antitrypsin deficiency: A single-center experience. Clin Transplant 2011; 25(5): 731-6.
[33]
Prachalias AA, Kalife M, Francavilla R, et al. Liver transplantation for alpha-1-antitrypsin deficiency in children. Transpl Int 2000; 13(3): 207-10.
[34]
Vennarecci G, Gunson BK, Ismail T, et al. Transplantation for end stage liver disease related to alpha 1 antitrypsin. Transplantation 1996; 61(10): 1488-95.
[35]
Jain AB, Patil V, Sheikh B, et al. Effect of liver transplant on pulmonary functions in adult patients with alpha 1 antitrypsin deficiency: 7 cases. Exp Clin Transplant 2010; 8(1): 4-8.
[36]
Koczulla R, Bittkowski N, Andress J, et al. The German registry of individuals with alpha-1-antitrypsin deficiency--a source for research on patient care. Pneumologie 2008; 62(11): 655-8.
[37]
Stoller JK, Brantly M. The challenge of detecting alpha-1 antitrypsin deficiency. COPD 2013; 10(Suppl. 1): 26-34.
[38]
Fromer L. Improving diagnosis and management of alpha-1 antitrypsin deficiency in primary care: Translating knowledge into action. COPD 2010; 7(3): 192-8.
[39]
Taliercio RM, Chatburn RL, Stoller JK. Knowledge of alpha-1 antitrypsin deficiency among internal medicine house officers and respiratory therapists: Results of a survey. Respir Care 2010; 55(3): 322-7.
[40]
Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med 2009; 360(26): 2749-57.
[41]
Campos M, Shmuels D, Walsh J. Detection of alpha-1 antitrypsin deficiency in the US. Am J Med 2012; 125(7): 623-4.
[42]
Bals R, Koczulla R, Kotke V, Andress J, Blackert K, Vogelmeier C. Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program. Respir Med 2007; 101(8): 1708-14.
[43]
Aboussouan LS, Stoller JK. Detection of alpha-1 antitrypsin deficiency: A review. Respir Med 2009; 103(3): 335-41.
[44]
Hogarth DK, Rachelefsky G. Screening and familial testing of patients for alpha 1-antitrypsin deficiency. Chest 2008; 133(4): 981-8.
[45]
Thelin T, Sveger T, McNeil TF. Primary prevention in a high-risk group: smoking habits in adolescents with homozygous alpha-1-antitrypsin deficiency (ATD). Acta Paediatr 1996; 85(10): 1207-12.
[46]
Coors ME, Moseley R, McGorray S. Informed consent process in Alpha-1 testing of at-risk children: views of parents and adults tested as children. COPD 2011; 8(1): 30-8.
[47]
Klitzman R. The impact of social contexts in testing for alpha-1 antitrypsin deficiency: The roles of physicians and others. Genet Test Mol Biomarkers 2009; 13(2): 269-76.
[48]
Sveger T, Thelin T, McNeil TF. Young adults with alpha 1-antitrypsin deficiency identified neonatally: Their health, knowledge about and adaptation to the high-risk condition. Acta Paediatr 1997; 86(1): 37-40.
[49]
Sveger T, Thelin T, McNeil TF. Neonatal alpha1-antitrypsin screening: Parents’ views and reactions 20 years after the identification of the deficiency state. Acta Paediatr 1999; 88(3): 315-8.
[50]
Sveger T, Thelin T. A future for neonatal alpha1-antitrypsin screening? Acta Paediatr 2000; 89(6): 628-31.
[51]
Carroll TP, O’Connor CA, Floyd O, et al. The prevalence of alpha-1 antitrypsin deficiency in Ireland. Respir Res 2011; 12: 91.
[52]
Corda L, Medicina D, La Piana GE, et al. Population genetic screening for alpha1-antitrypsin deficiency in a high-prevalence area. Respiration 2011; 82(5): 418-25.
[53]
Topic A, Prokic D, Stankovic I. Alpha-1-antitrypsin deficiency in early childhood. Fetal Pediatr Pathol 2011; 30(5): 312-9.
[54]
Wewers MD, Casolaro MA, Crystal RG. Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy. Am Rev Respir Dis 1987; 135(3): 539-43.
[55]
Seersholm N, Wencker M, Banik N, et al. Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group. Eur Respir J 1997; 10(10): 2260-3.
[56]
Wencker M, Banik N, Buhl R, Seidel R, Konietzko N. Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group. Eur Respir J 1998; 11(2): 428-33.
[57]
Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Am J Respir Crit Care Med 1998; 158(1): 49-59.
[58]
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(5 Pt 1): 1468-72.
[59]
Dirksen A, Piitulainen E, Parr DG, et al. Exploring the role of CT densitometry: A randomised study of augmentation therapy in alpha1-antitrypsin deficiency. Eur Respir J 2009; 33(6): 1345-53.

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