{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:48:46Z","timestamp":1789076926801,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"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":["Liver International"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    \u2010rs738409\u2010G variant was the first common variant associated with hepatic fat accumulation and progression of metabolic dysfunction\u2010associated steatotic liver disease (MASLD). Nevertheless, to date, the clinical translation of this discovery has been minimal because it has not yet been clearly demonstrated where the genetic information may play an independent and additional role in clinical risk prediction. In this mini\u2010review, we will discuss the most relevant evidence regarding the potential integration of the\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    variant into scores and algorithms for liver disease diagnostics and risk stratification, specifically focusing on MASLD but also extending to liver diseases of other etiologies. The\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    variant adds little in diagnosing the current state of the disease, whether in terms of presence\/absence of metabolic dysfunction\u2010associated steatohepatitis or the stage of fibrosis. While it can play an important role in prediction, allowing for the early definition of risk profiles that enable tailored monitoring and interventions over time, this is most valuable when applied to populations with relatively high pre\u2010test probability of having significant fibrosis based on either non\u2010invasive tests (e.g. Fibrosis\u20104) or demographics (e.g. diabetes). Indeed, in this context, integrating FIB4 with the\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    genotype can refine risk stratification, though there is still no evidence that genetic information adds to liver stiffness determined by elastography. Similarly, in patients with known liver cirrhosis, knowing the\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    genotype can play a role in predicting the risk of hepatocellular carcinoma, while more doubts remain about the risk of decompensation.\n                  <\/jats:p>","DOI":"10.1111\/liv.16103","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T06:09:36Z","timestamp":1726466976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integrating\n                    <scp>\n                      <i>PNPLA3<\/i>\n                    <\/scp>\n                    into clinical risk prediction"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-6066","authenticated-orcid":false,"given":"Vincent L.","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1138-1967","authenticated-orcid":false,"given":"Umberto","family":"Vespasiani\u2010Gentilucci","sequence":"additional","affiliation":[{"name":"Research Unit of Hepatology Universit\u00e0 Campus Bio\u2010Medico di Rome  Rome Italy"},{"name":"Hepatology and Clinical Medicine Unit Fondazione Policlinico Universitario Campus\u2010Biomedico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.257"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.02.011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.079749"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23768"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.023"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037827"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.03.045"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2010.30185"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15438"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12719"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.488"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3417"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02534.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2012.05.006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31910"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0041-8"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.34221"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26767"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.02.030"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.06.005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-021-10200-y"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.031"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000323"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.009"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.02.011"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.05.046"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2023.01.020"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-022-00934-0"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.038"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31238"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31032"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100262"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000896"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.024"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15678"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.05.056"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1877"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.02.026"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.01.040"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.02.022"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx246"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.02.031"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1610570"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237430"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18099"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15697"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15554"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3855"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.11.024"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000466"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02553-8"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12695"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S355540"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.036"},{"key"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