{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:43:39Z","timestamp":1790689419752,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Fatty Liver Disease is a major health problem worldwide. We can distinguish liver steatosis as non-associated or associated with chronic\/acute alcohol consumption. These two entities share similar stages ranging from hepatic fat storage (namely, steatosis) to inflammation, necrosis, and fibrosis until hepatocellular carcinoma (HCC). Over time, \u201cMetabolic Associated Fatty Liver Disease\u201d (MAFLD) has replaced nonalcoholic fatty liver disease (NAFLD) nomenclature and has included cardiometabolic criteria in these patients definition. Thus, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia are MAFLD features and are of the metabolic syndrome. Importantly, there is not a specific treatment for MAFLD, but there are therapeutic strategies that act on metabolic dysfunction related to MAFLD. They can reduce the progression of liver fibrosis and its complications. Materials and Methods: For all these reasons, we conducted a narrative review of the literature, and we focused on metabolic dysfunction related to MAFLD, with a special regard for cholesterol metabolism. Results: MAFLD is a recently redefined condition that better describes the metabolism derangement responsible for fatty liver disease. This distinguishes MAFLD from NAFLD. In fact, the diagnostic criteria for MAFLD require the presence of liver steatosis together with at least one of the following: obesity, T2DM, or evidence of metabolic disorder such as hypertriglyceridemia, low high-density lipoprotein cholesterol, or hypertension. As a result, MAFLD is closely linked to an increased cardiometabolic risk. Current therapeutic approaches can be used to reduce this risk, focusing on lifestyle interventions and pharmacological strategies. Several treatments in patients diagnosed with MAFLD are mainly cholesterol-lowering remedies. Among these, Pro-protein Convertase Subtilisin\/Kexin type 9 inhibitors (PCSK9i) show the most promising efficacy profile but data on liver fibrosis are lacking. Agonists of GLP-1 receptor, Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have a \u201c multi-hit \u201c action allowing their use also in diabetic patients with MAFLD. Conclusions: Lifestyle modifications, some nutraceuticals, statins, incretins, and PCSK9i have changed the natural course and significantly improved the cardiometabolic outcomes of MAFLD. Emerging cholesterol-lowering drugs, such as Bempedoic acid, can overcome low compliance to statins\u2019 use and their controversial effect on liver fibrosis. Finally, medications targeting insulin resistance allow for strategic interventions of the convoluted pathophysiology of MAFLD in multiple steps, with the potential to reduce liver steatosis, inflammation, and necrosis and, sometimes even to reverse liver fibrosis.<\/jats:p>","DOI":"10.3390\/medicina61030387","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:04:28Z","timestamp":1740391468000},"page":"387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Management of Cardiometabolic Risk in MAFLD: Therapeutic Strategies to Modulate Deranged Metabolism and Cholesterol Levels"],"prefix":"10.3390","volume":"61","author":[{"given":"Annalisa","family":"Pezzoli","sequence":"first","affiliation":[{"name":"Internal Medicine Unit, \u201c Madonna del Soccorso\u201d General Hospital, 63074 San Benedetto del Tronto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-1524","authenticated-orcid":false,"given":"Ludovico","family":"Abenavoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialaura","family":"Scarcella","sequence":"additional","affiliation":[{"name":"Anesthesia, Intensive Care and Nutritional Science, Azienda Ospedaliera \u201cSanta Maria\u201d, Via Tristano di Joannuccio, 05100 Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Rasetti","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, \u201c Madonna del Soccorso\u201d General Hospital, 63074 San Benedetto del Tronto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Svegliati Baroni","sequence":"additional","affiliation":[{"name":"\u201cHepatic Damage and Transplantation \u201c Unit, Polytechnics University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tack","sequence":"additional","affiliation":[{"name":"Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-1118","authenticated-orcid":false,"given":"Emidio","family":"Scarpellini","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, \u201c Madonna del Soccorso\u201d General Hospital, 63074 San Benedetto del Tronto, Italy"},{"name":"Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.3748\/wjg.v23.i36.6549","article-title":"Treatment options for alcoholic and non-alcoholic fatty liver disease: A review","volume":"23","author":"Singh","year":"2017","journal-title":"World J. 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