{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:51:28Z","timestamp":1776286288701,"version":"3.50.1"},"reference-count":223,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.<\/jats:p>","DOI":"10.3390\/ijms241310718","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"10718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-2202","authenticated-orcid":false,"given":"Marta","family":"Alonso-Pe\u00f1a","sequence":"first","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Del Barrio","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-5037","authenticated-orcid":false,"given":"Ana","family":"Peleteiro-Vigil","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Jimenez-Gonzalez","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Santos-Laso","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8864-3833","authenticated-orcid":false,"given":"Maria Teresa","family":"Arias-Loste","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Iruzubieta","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-0172","authenticated-orcid":false,"given":"Javier","family":"Crespo","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqu\u00e9s de Valdecilla University Hospital, 39011 Santander, Spain"},{"name":"Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.metabol.2016.02.014","article-title":"Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease","volume":"65","author":"Mota","year":"2016","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/hep4.1134","article-title":"Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies","volume":"2","author":"Nasr","year":"2018","journal-title":"Hepatol. 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