{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:03:38Z","timestamp":1789844618817,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heterozygous SERPINA1 genotypes (MZ, SZ) have historically been regarded as carrier states with limited liver relevance. Emerging evidence suggests increased liver injury, but the magnitude of risk remains uncertain. We synthesized evidence on heterozygous SERPINA1 liver phenotypes to quantify this risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a systematic review of bibliographic databases from inception to 21 October 2025 for studies reporting liver outcomes in MZ or SZ genotypes. Outcomes were grouped into metabolic comorbidities, biochemical markers, and clinical liver disease. Random\u2010effects meta\u2010analyses pooled mean differences (MDs) and odds ratios (ORs); risk of bias was assessed with established tools (PROSPERO CRD420251165586).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010six studies including 27,933 heterozygotes and 547,961 controls met inclusion criteria. BMI (MD \u22120.09 [\u22120.20\u20130.02]) and steatosis risk (OR 1.09 [0.74\u20131.60]) were comparable between groups. Heterozygotes had modestly higher liver enzymes (ALT MD 1.03 [0.41\u20131.66]; AST MD 0.68 [0.51\u20130.85]; ALP MD 2.58 [1.58\u20133.58]) and higher odds of abnormal ALT (OR 1.18 [1.11\u20131.25]), AST (OR 1.16 [1.07\u20131.26]), and ALP (OR 1.41 [1.18\u20131.68]). They had significantly increased odds of fibrosis (OR 2.14 [1.52\u20133.02]), cirrhosis (OR 2.24 [1.73\u20132.91]), and liver transplantation (OR 2.28 [1.45\u20133.59]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Heterozygous\n                      <jats:styled-content style=\"fixed-case\">SERPINA1<\/jats:styled-content>\n                      genotypes are bona fide liver risk states, with effect sizes comparable to established genetic and environmental determinants.\n                      <jats:styled-content style=\"fixed-case\">MZ<\/jats:styled-content>\n                      \/\n                      <jats:styled-content style=\"fixed-case\">SZ<\/jats:styled-content>\n                      heterozygosity should be recognized as moderate\u2010penetrance liver susceptibility genotypes in chronic liver disease risk assessment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70814","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T14:07:32Z","timestamp":1783865252000},"page":"430-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Meta\u2010Analysis: Redefining Liver Disease Risk in Heterozygous Alpha\u20101 Antitrypsin Deficiency"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-6146","authenticated-orcid":false,"given":"Adam M.","family":"Syanda","sequence":"first","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine Imperial College London  London UK"},{"name":"Department of Population Health Sciences School of Life Course and Population Sciences, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Georgantaki","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riona T. T.","family":"Linn","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Agbai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Tahir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manako","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Thompson","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Molokhia","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences School of Life Course and Population Sciences, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Tamir","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954\u20106820.1964.tb00567.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954\u20106820.1974.tb08170.x"},{"issue":"6","key":"e_1_2_10_4_1","first-page":"934","article-title":"Cirrhosis Associated With Alpha\u20101\u2010Antitrypsin Deficiency: A Previously Unrecognized Inherited Disorder","volume":"73","author":"Sharp H. 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