{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:43:01Z","timestamp":1783723381332,"version":"3.55.0"},"reference-count":75,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 1382 (ID 403224013) and STR 1095\/6\u20131"],"award-info":[{"award-number":["SFB 1382 (ID 403224013) and STR 1095\/6\u20131"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>Alpha-1 antitrypsin deficiency (AATD) arises due to inherited variants in SERPINA1, the AAT gene that impairs the production or secretion of this hepatocellular protein and leads to a gain-of-function liver proteotoxicity. Homozygous Pi*Z pathogenic variant (Pi*ZZ genotype) is the leading cause of severe AATD. It manifests in 2 to 10% of carriers as neonatal cholestasis and 20 to 35% of adults as significant liver fibrosis. Both children and adults may develop an end-stage liver disease requiring liver transplantation. Heterozygous Pi*Z pathogenic variant (Pi*MZ genotype) constitutes an established disease modifier. Our review summarizes the natural history and management of subjects with both pediatric and adult AATD-associated liver disease. Current findings from a phase 2 clinical trial indicate that RNA silencing may constitute a viable therapeutic approach for adult AATD. In conclusion, AATD is an increasingly appreciated pediatric and adult liver disorder that is becoming an attractive target for modern pharmacologic strategies.<\/jats:p>","DOI":"10.1055\/a-2122-7674","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T22:53:50Z","timestamp":1688511230000},"page":"258-266","source":"Crossref","is-referenced-by-count":15,"title":["Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency"],"prefix":"10.1055","volume":"43","author":[{"given":"Mathias","family":"Ruiz","sequence":"additional","affiliation":[{"name":"H\u00e9patologie, Gastroent\u00e9rologie et Nutrition P\u00e9diatriques, H\u00f4pital Femme M\u00e8re Enfant, Hospices civils de Lyon, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie-Nutrition P\u00e9diatriques et Unit\u00e9 d'H\u00e9patologie P\u00e9diatrique H\u00f4pital Universitaire Necker-Enfants Malades, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Schrader","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Pons","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Socha","sequence":"additional","affiliation":[{"name":"The Children's Memorial Health Institute, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Al. Dzieci Polskich, Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Krag","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Sturm","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology, University Children's Hospital T\u00fcbingen, Member Center of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Bouchecareilh","sequence":"additional","affiliation":[{"name":"University of Bordeaux, CNRS, INSERM, BRIC, U1312, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Strnad","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"issue":"15","key":"ref1","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1056\/NEJMra1910234","article-title":"Alpha1-antitrypsin deficiency","volume":"382","author":"P Strnad","year":"2020","journal-title":"N Engl J Med"},{"issue":"04","key":"ref2","first-page":"184","article-title":"PI S and PI Z alpha-1 antitrypsin deficiency worldwide. 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