{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:56:09Z","timestamp":1791370569498,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metabolic dysfunction\u2010associated steatotic disease (MASLD) affects increasing numbers of patients worldwide. The\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      p.I148M variant represents a major genetic determinant of MASLD progression. The loss\u2010of\u2010function\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      polymorphism rs72613567 was reported in turn to be hepatoprotective.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>\n                      We analysed blood samples of 507 patients recruited within the Fatty Liver Assessment in Germany (FLAG) study, of whom 476 (255 males, age 56\u00a0years) were genotyped. FLAG is a multicenter real\u2010world MASLD cohort covering secondary and tertiary healthcare levels. The\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      p.I148M and the\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      rs72613567 polymorphisms were genotyped using allelic discrimination assays. The control cohort comprised 174 individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      p.I148M variant was prevalent among FLAG patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001 for the departure from Hardy\u2013Weinberg equilibrium) and increased the risk of developing MASLD (common OR\u00a0=\u00a02.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a06.238e\u201009). It was associated with increased ALT and AST, lower serum triglyceride concentrations, and independently with liver stiffness \u2265\u00a09.1\u00a0kPa after adjustment for BMI and diabetes (OR\u00a0=\u00a02.57,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.01). Carriers of the\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      rs72613567 variant had lower AST.\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      heterozygotes had lower FIB\u20104 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.028) and lower liver stiffness (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.034). Among carriers of the\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      p.148M allele, the presence of the\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      variant was associated with lower ALT (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.023) and AST (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.041); however,\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      did not abrogate the association of\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      with liver fibrosis (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.013).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      By analysing a real\u2010world MASLD cohort in Germany, we further underscore the role of the\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      variant as the central genetic trigger and modulator of MASLD. The\n                      <jats:italic>HSD17B13<\/jats:italic>\n                      polymorphism may exert protective effects in MASLD and could attenuate some\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      \u2010associated effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ueg2.70298","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:47:57Z","timestamp":1791370077000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Dysfunction\u2010Associated Steatotic Disease and Genetic Risk in Germany\u2014An Observational Real\u2010World Cohort Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-0777","authenticated-orcid":false,"given":"Marcin","family":"Krawczyk","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Transplant Medicine Medical Faculty University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-0329","authenticated-orcid":false,"given":"Frank","family":"Gr\u00fcnhage","sequence":"additional","affiliation":[{"name":"KRH Klinikum Siloah  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Schubert","sequence":"additional","affiliation":[{"name":"Gastroenterologie am Bayerischen Platz  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nektarios","family":"Dikopoulos","sequence":"additional","affiliation":[{"name":"Gastroenterologische Schwerpunktpraxis  Dornstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Schwenzer","sequence":"additional","affiliation":[{"name":"Bauchzentrum Biesdorf  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Muche","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Campus Benjamin Franklin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-4064","authenticated-orcid":false,"given":"Johannes","family":"Wiegand","sequence":"additional","affiliation":[{"name":"Division of Hepatology Department of Medicine II Leipzig University Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Felten","sequence":"additional","affiliation":[{"name":"Gastroenterologische Praxis  Herne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Heyne","sequence":"additional","affiliation":[{"name":"Leberzentrum am Checkpoint  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7218-4548","authenticated-orcid":false,"given":"Patrick","family":"Ingiliz","sequence":"additional","affiliation":[{"name":"APHP H\u00f4pital Henri\u2010Mondor Hepatology Department Inserm U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Magen\u2010Darm\u2010Zentrum Wiener Platz  K\u00f6ln Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Stein","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Infektiologie und Hepatologie Magdeburg  Magdeburg\u2010Altstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5531-175X","authenticated-orcid":false,"given":"Susanne N.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 2 Saarland University Hospital  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-0480","authenticated-orcid":false,"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I Hospital of the Goethe University Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3076-3960","authenticated-orcid":false,"given":"Peter","family":"Buggisch","sequence":"additional","affiliation":[{"name":"IFI Institut f\u00fcr interdisziplin\u00e4re Medizin  Hamburg Germany"},{"name":"bng, Berufsverband Niedergelassener Gastroenterologen e.V  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4450-7201","authenticated-orcid":false,"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[{"name":"Center for Health Economics Research Hannover (CHERH) Hannover Medical School (MHH)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Geier","sequence":"additional","affiliation":[{"name":"Division of Hepatology Department of Medicine II University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf Peter","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Gastroenterologie am Bayerischen Platz  Berlin Germany"},{"name":"IFI Institut f\u00fcr interdisziplin\u00e4re Medizin  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-4703","authenticated-orcid":false,"given":"J\u00f6rn M.","family":"Schattenberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 2 Saarland University Hospital  Homburg Germany"},{"name":"Saarland University  Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2412865"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.12.053"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(24)00318\u20108"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468\u20101253(26)00087\u20107"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2026.101957"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.031"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.036"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.11.049"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.053"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.05.007"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.02.020"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70240"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m111.290114"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010016\u20103944\u20101"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2016.00009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1712191"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17292"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17638"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2020.100168"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468\u20101253(20)30357\u20105"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.05.033"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.042"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41591-026-04496-2","article-title":"Prospective Validation of Imaging and Serum Diagnostic Biomarkers of Steatohepatitis and Fibrosis in MASLD: The LITMUS Imaging Study","author":"Pavlides M.","year":"2026","journal-title":"Nature Medicine"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.p067454"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(18)30154\u20102"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.10.048"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100212\u20100"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.16106"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.05.052"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.023"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12913\u2010016\u20101289\u20106"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12937"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.p089953"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103558"},{"key":"e_1_2_8_37_1","article-title":"Genetic and Non\u2010Genetic Drivers of Histological Progression and Regression in MASLD","author":"Vilar\u2010Gomez E.","year":"2025","journal-title":"Journal of Hepatology"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202009_22842"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.12.046"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2402341"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2309000"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2413258"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","DOI":"10.1111\/apt.70888","article-title":"Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction\u2010Associated Steatohepatitis\u2010Reanalysis of Fibrosis Stage 2\u20103 Subset","author":"Mironova M.","year":"2026","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2026.06.003"}],"container-title":["United European Gastroenterology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ueg2.70298","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ueg2.70298","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ueg2.70298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:47:59Z","timestamp":1791370079000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ueg2.70298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ueg2.70298"],"URL":"https:\/\/doi.org\/10.1002\/ueg2.70298","archive":["Portico"],"relation":{},"ISSN":["2050-6406","2050-6414"],"issn-type":[{"value":"2050-6406","type":"print"},{"value":"2050-6414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"article-number":"e70298"}}