{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:23:55Z","timestamp":1785464635900,"version":"3.56.0"},"reference-count":74,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,5]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Alpha\u20101 antitrypsin liver disease (AATLD) occurs in a subset of patients with alpha\u20101 antitrypsin deficiency. Risk factors for disease progression and specific pathophysiologic features are not well known and validated non\u2010invasive assessments for disease severity are lacking. Currently, there are no approved treatments for AATLD.<\/jats:p><\/jats:sec>Aims<\/jats:title>To outline existing understanding of AATLD and to identify knowledge gaps critical to improving clinical trial design and development of new treatments.<\/jats:p><\/jats:sec>Methods<\/jats:title>This report was developed following a multi\u2010stakeholder forum organised by the Alpha\u20101 Antitrypsin Deficiency Related Liver Disease Expert Panel in which experts presented an overview of the available literature on this topic.<\/jats:p><\/jats:sec>Results<\/jats:title>AATLD results from a \u2018gain of toxic function\u2019 and primarily manifests in those with the homozygous Pi*ZZ genotype. Accumulation of misfolded \u2018Z\u2019 AAT protein in liver cells triggers intracellular hepatocyte injury which may ultimately lead to hepatic fibrosis. Male gender, age over 50\u2009years, persistently elevated liver tests, concomitant hepatitis B or C virus infection, and metabolic syndrome, including obesity and type 2 diabetes mellitus, are known risk factors for adult AATLD. While the gold standard for assessing AATLD disease activity is liver histology, less invasive measures with low intra\u2010 and inter\u2010observer variability are needed. Measurement of liver stiffness shows promise; validated thresholds for staging AATLD are in development. Such advances will help patients by enabling risk stratification and personalised surveillance, along with streamlining the development process for novel therapies.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This inaugural forum generated a list of recommendations to address unmet needs in the field of AATLD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17967","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T09:15:47Z","timestamp":1711098947000},"page":"1183-1195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Review article: New developments in biomarkers and clinical drug development in alpha\u20101 antitrypsin deficiency\u2010related liver disease"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-9991","authenticated-orcid":false,"given":"Rohit","family":"Loomba","sequence":"first","affiliation":[{"name":"Division of 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