{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:00:33Z","timestamp":1792155633140,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It is unclear whether the <jats:italic>patatin\u2010like phospholipase domain\u2010containing protein 3<\/jats:italic> (<jats:italic>PNPLA3<\/jats:italic>) rs738409 C\u2010to\u2010G single nucleotide polymorphism, resulting in the substitution of isoleucine to methionine at position 148 (I148M), impedes regression of hepatic steatosis when treating non\u2010alcoholic fatty liver disease (NAFLD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Investigate if carriage of the <jats:italic>PNPLA3<\/jats:italic> 148M allele affects the anti\u2010steatotic efficacy of all possible anti\u2010NAFLD interventions, identify gaps in current knowledge and provide guidance for individual treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Research available in public databases was searched up to 13 November 2022. Studies were included if a treatment in NAFLD patients decreased hepatic steatosis in the pooled patient group or a <jats:italic>PNPLA3<\/jats:italic> I148M polymorphism subgroup (II\/IM\/MM). The risk of bias was assessed using the Cochrane Risk\u2010Of\u2010Bias 2 Tool and the Newcastle\u2013Ottawa Scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Moderate evidence indicates that NAFLD patients homozygous for the <jats:italic>PNPLA3<\/jats:italic> 148M allele benefit less or not at all from omega\u20103 carboxylic acids to decrease liver fat, while the <jats:italic>PNPLA3<\/jats:italic> 148I allele shows moderate benefit. Low evidence suggests that interventions employing lifestyle changes are more effective to reduce liver fat in NAFLD patients homozygous for the <jats:italic>PNPLA3<\/jats:italic> 148M allele compared to patients with wild\u2010type <jats:italic>PNPLA3<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NAFLD patients homozygous for the <jats:italic>PNPLA3<\/jats:italic> 148M allele might not benefit from omega\u20103 carboxylic acids to reduce hepatic steatosis in contrast to patients with wild\u2010type <jats:italic>PNPLA3<\/jats:italic>. Instead, patients with two <jats:italic>PNPLA3<\/jats:italic> 148M alleles should be especially advised to adopt lifestyle changes. Genotyping for <jats:italic>PNPLA3<\/jats:italic> I148M should be encouraged in therapeutic studies for NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Registration Number (<jats:styled-content style=\"fixed-case\">Prospero<\/jats:styled-content>)<\/jats:title><jats:p>CRD42022375028.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15533","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T12:39:53Z","timestamp":1675168793000},"page":"975-988","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["<scp>PNPLA3 I148M<\/scp> and response to treatment for hepatic steatosis: A systematic review"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8399-5872","authenticated-orcid":false,"given":"Joost","family":"Boeckmans","sequence":"first","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato\u2010Cosmetology Faculty of Medicine and Pharmacy, 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