{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:07:19Z","timestamp":1790946439529,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014931","name":"Arrowhead Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014931","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001448","name":"Alpha-1 Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001448","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The course of adults with ZZ alpha\u20101\u2010antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective cohort, including protocol liver biopsies, was enrolled to address these questions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0\u20136). Also, 51% of the 96 subjects had Ishak score &gt;1 fibrosis (49% Ishak 0\u20131, 36% Ishak 2\u20133 and 15% \u22654). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (<jats:italic>p<\/jats:italic>\u2009=\u2009.002) and increased diffuse cytoplasmic Z polymer on biopsy (<jats:italic>p<\/jats:italic>\u2009=\u2009.0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (<jats:italic>p<\/jats:italic>\u2009=\u2009.007) and increased periportal inflammation on histopathology (<jats:italic>p<\/jats:italic>\u2009=\u2009.004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16094","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T12:16:52Z","timestamp":1726143412000},"page":"3204-3213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fibrosis, biomarkers and liver biopsy in <scp>AAT<\/scp> deficiency and relation to liver Z protein polymer accumulation"],"prefix":"10.1111","volume":"44","author":[{"given":"Anandini","family":"Suri","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Saint Louis University  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zidong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Health and Clinical 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Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Loomba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Internal Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Internal Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Clinical Trial Unit Saint Louis University  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Internal Medicine 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