{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:48:49Z","timestamp":1790812129539,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["CUP u.o.\u2014NRRP M6C2I2.1 NextGenerationEU"],"award-info":[{"award-number":["CUP u.o.\u2014NRRP M6C2I2.1 NextGenerationEU"]}]},{"name":"Italian Ministry of University and Research","award":["PNRR-MAD-2022-12375721"],"award-info":[{"award-number":["PNRR-MAD-2022-12375721"]}]},{"name":"Italian Ministry of University and Research","award":["CUP: C63C22001520006"],"award-info":[{"award-number":["CUP: C63C22001520006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Severe hypertriglyceridemia (SHTG) is associated with acute pancreatitis, metabolic dysfunction, and increased cardiovascular risk. Its genetic architecture ranges from rare biallelic variants causing familial chylomicronemia syndrome (FCS) to more prevalent polygenic or multifactorial chylomicronemia syndromes (MCS). Methods: We systematically reviewed scientific literature up to 2025 for studies reporting genetic data, clinical features, or therapeutic outcomes in adults with triglycerides (TG) \u2265 500 mg\/dL. Extracted data were synthesized for genotype, polygenic risk score (PRS), TG levels, metabolic comorbidities, hepatic steatosis, pancreatitis, and treatment response. Results: Ten studies (n = 2521) were included. FCS due to biallelic LPL, APOC2, GPIHBP1, or LMF1 variants accounted for &lt;5% of cases and showed extreme TG elevations (&gt;2800 mg\/dL) with pancreatitis prevalence (&gt;70%). APOA5, APOC3, and APOB variants were associated with intermediate TG levels and high rates of metabolic dysfunction-associated steatotic liver disease (MASLD). Polygenic hypertriglyceridemia represented ~70\u201380% of cases, with TG \u2248 2200 mg\/dL and pancreatitis prevalence 15\u201320%, largely modulated by metabolic triggers. MASLD was present in &gt;70% of polygenic cases, supporting a \u201ctwo-hit\u201d model where hepatic overproduction of TG-rich lipoproteins amplifies TG excess. Interventional trials demonstrated TG reductions with APOC3 antisense therapy (70\u201380%) and ANGPTL3 inhibition (50\u201355%), while GLP-1RA significantly reduced hepatic fat (30\u201335%) and resolved NASH in up to 59% of patients. Conclusions: SHTG displays a genotype\u2013phenotype gradient: FCS is linked to recurrent pancreatitis, whereas polygenic\/MCS forms are closely associated with MASLD and metabolic dysfunction. These findings support a precision-medicine approach integrating genetic testing and PRS-guided strategies\u2014prioritizing APOC3\/ANGPTL3 inhibitors for FCS and combined TG-lowering plus metabolic therapies for MCS\u2014to reduce pancreatitis recurrence and liver disease.<\/jats:p>","DOI":"10.3390\/genes16111377","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:44:55Z","timestamp":1762865095000},"page":"1377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic Assessment and Clinical Correlates in Severe Hypertriglyceridemia: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6875-9133","authenticated-orcid":false,"given":"Carmine","family":"De Luca","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ciciola","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"D\u2019Errico","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0618-7940","authenticated-orcid":false,"given":"Maria Donata","family":"Di Taranto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, CEINGE Advanced Biotechnologies S.C. A R.L, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-383X","authenticated-orcid":false,"given":"Giuliana","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, CEINGE Advanced Biotechnologies S.C. A R.L, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Gross","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Garn","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-5544","authenticated-orcid":false,"given":"Gabriella","family":"Iannuzzo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-3819","authenticated-orcid":false,"given":"Matteo","family":"Di Minno","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Calcaterra","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrg2481","article-title":"Plasma lipoproteins: Genetic influences and clinical implications","volume":"10","author":"Hegele","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s12944-024-02297-5","article-title":"Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans","volume":"23","author":"Lesogor","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.atherosclerosis.2018.06.814","article-title":"Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an \u201cFCS score\u201d","volume":"275","author":"Moulin","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1056\/NEJMoa1400283","article-title":"Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia","volume":"373","author":"Gaudet","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S2213-8587(13)70191-8","article-title":"The polygenic nature of hypertriglyceridaemia: Implications for definition, diagnosis, and management","volume":"2","author":"Hegele","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jacl.2012.06.005","article-title":"The interaction of familial and secondary causes of hypertriglyceridemia: Role in pancreatitis","volume":"6","author":"Brunzell","year":"2012","journal-title":"J. Clin. Lipidol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lindberg, D.A. (2009). Acute pancreatitis and hypertriglyceridemia. Gastroenterol. Nurs., 32.","DOI":"10.1097\/SGA.0b013e31819de3e0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/ATVBAHA.119.313286","article-title":"Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid","volume":"40","author":"Mason","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12944-025-02658-8","article-title":"Rates of acute pancreatitis and cardiovascular events among adults with severe or extreme hypertriglyceridemia in US clinical practice","volume":"24","author":"Baum","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.atherosclerosissup.2017.05.003","article-title":"The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia","volume":"30","year":"2017","journal-title":"Atherosclerosis. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/CS20070308","article-title":"Apolipoprotein C-III: Understanding an emerging cardiovascular risk factor","volume":"114","author":"Ooi","year":"2008","journal-title":"Clin. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1358\/dot.2018.54.12.2899384","article-title":"Volanesorsen for treatment of patients with familial chylomicronemia syndrome","volume":"54","author":"Warden","year":"2018","journal-title":"Drugs Today"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Alves, M., Laranjeira, F., and Correia-da-Silva, G. (2024). Understanding Hypertriglyceridemia: Integrating Genetic Insights. Genes., 15.","DOI":"10.3390\/genes15020190"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dron, J.S., and Hegele, R.A. (2020). Genetics of Hypertriglyceridemia. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00455"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e13841","DOI":"10.1111\/eci.13841","article-title":"Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials","volume":"52","author":"Calcaterra","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0021-9150(88)90288-2","article-title":"Metabolism of apolipoprotein C-III in normolipemic human subjects","volume":"69","author":"Malmendier","year":"1988","journal-title":"Atherosclerosis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1172\/JCI86610","article-title":"ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors","volume":"126","author":"Gordts","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1308027","article-title":"Loss-of-function mutations in APOC3 and risk of ischemic vascular disease","volume":"371","author":"Jorgensen","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"The TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute (2014). Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N. Engl. J. Med., 371, 22\u201331.","DOI":"10.1056\/NEJMoa1307095"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Boren, J., Packard, C.J., and Taskinen, M.R. (2020). The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00474"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Guan, Y., Hou, X., Tian, P., Ren, L., Tang, Y., Song, A., Zhao, J., Gao, L., and Song, G. (2021). Elevated Levels of Apolipoprotein CIII Increase the Risk of Postprandial Hypertriglyceridemia. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.646185"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Behbodikhah, J., Ahmed, S., Elyasi, A., Kasselman, L.J., De Leon, J., Glass, A.D., and Reiss, A.B. (2021). Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites, 11.","DOI":"10.3390\/metabo11100690"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.tem.2013.04.001","article-title":"The regulation of ApoB metabolism by insulin","volume":"24","author":"Haas","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S2213-8587(14)70032-4","article-title":"Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome","volume":"2","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/hep.31325","article-title":"Surgical Treatments of Hepatobiliary Cancers","volume":"73","author":"Gunasekaran","year":"2021","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1999\u20132014 e1991","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/MED.0000000000000903","article-title":"An overview of persistent chylomicronemia: Much more than meets the eye","volume":"32","author":"Larouche","year":"2025","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Guo, Z., Wu, D., Mao, R., Yao, Z., Wu, Q., and Lv, W. (2025). Global burden of MAFLD, MAFLD related cirrhosis and MASH related liver cancer from 1990 to 2021. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-91312-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s11883-023-01140-z","article-title":"Updates in Drug Treatment of Severe Hypertriglyceridemia","volume":"25","author":"Schwarz","year":"2023","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1056\/NEJMoa1701329","article-title":"Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides","volume":"377","author":"Graham","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1056\/NEJMoa2413258","article-title":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis","volume":"392","author":"Sanyal","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S2468-1253(23)00068-7","article-title":"Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial","volume":"8","author":"Loomba","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szekeres, Z., Nagy, A., Jahner, K., and Szabados, E. (2024). Impact of Selected Glucagon-like Peptide-1 Receptor Agonists on Serum Lipids, Adipose Tissue, and Muscle Metabolism\u2014A Narrative Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158214"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2165","DOI":"10.1002\/hsr2.2165","article-title":"The Cochrane risk of bias assessment tool 2 (RoB 2) versus the original RoB: A perspective on the pros and cons","volume":"7","author":"Nejadghaderi","year":"2024","journal-title":"Health Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jacl.2018.10.006","article-title":"Severe hypertriglyceridemia is primarily polygenic","volume":"13","author":"Dron","year":"2019","journal-title":"J. Clin. Lipidol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1161\/ATVBAHA.122.318445","article-title":"Genetic Testing for Hypertriglyceridemia in Academic Lipid Clinics: Implications for Precision Medicine-Brief Report","volume":"42","author":"Deshotels","year":"2022","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1056\/NEJMoa1715944","article-title":"Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome","volume":"381","author":"Witztum","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1056\/NEJMoa2402309","article-title":"Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk","volume":"390","author":"Bergmark","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liao, C., Liang, X., Zhang, X., and Li, Y. (2023). The effects of GLP-1 receptor agonists on visceral fat and liver ectopic fat in an adult population with or without diabetes and nonalcoholic fatty liver disease: A systematic review and meta-analysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0289616"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1001\/jamacardio.2023.2921","article-title":"Longer-Term Efficacy and Safety of Evinacumab in Patients with Refractory Hypercholesterolemia","volume":"8","author":"Rosenson","year":"2023","journal-title":"JAMA Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s44337-025-00329-2","article-title":"fficacy and safety of Olezarsen in treating hypertriglyceridemia: A systematic review and meta-analysis of randomized controlled trials","volume":"2","author":"Saddique","year":"2025","journal-title":"Discov. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101365","DOI":"10.1016\/j.gim.2025.101365","article-title":"Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society","volume":"27","author":"Ariza","year":"2025","journal-title":"Genet. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101092","DOI":"10.1016\/j.molmet.2020.101092","article-title":"Dysregulated lipid metabolism links NAFLD to cardiovascular disease","volume":"42","author":"Deprince","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"282\u2013292 e284","DOI":"10.1016\/j.jacl.2020.04.004","article-title":"Effect of pharmacist interventions on reducing low-density lipoprotein cholesterol (LDL-C) levels: A systematic review and meta-analysis","volume":"14","author":"Dixon","year":"2020","journal-title":"J. Clin. Lipidol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1002\/oby.20366","article-title":"A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population","volume":"21","author":"Verrijken","year":"2013","journal-title":"Obesity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1194\/jlr.R800053-JLR200","article-title":"Hepatic triacylglycerol accumulation and insulin resistance","volume":"50","author":"Nagle","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"oeaf018","DOI":"10.1093\/ehjopen\/oeaf018","article-title":"Remnant cholesterol concentrations best explain the cardiovascular benefit of APOC3 genetic inhibition: A drug target Mendelian randomization study","volume":"5","author":"Gagnon","year":"2025","journal-title":"Eur. Heart J. Open"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e002376","DOI":"10.1161\/CIRCGEN.118.002376","article-title":"Rare Protein-Truncating Variants in APOB, Lower Low-Density Lipoprotein Cholesterol, and Protection Against Coronary Heart Disease","volume":"12","author":"Peloso","year":"2019","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11883-023-01080-8","article-title":"APOC-III: A Gatekeeper in Controlling Triglyceride Metabolism","volume":"25","author":"Giammanco","year":"2023","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jianu, N., Nitu, E.T., Merlan, C., Nour, A., Buda, S., Suciu, M., Luca, S.A., Sbarcea, L., Andor, M., and Buda, V. (2025). A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part II. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081150"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/MOL.0000000000000849","article-title":"Recent Apolipoprotein CIII trials","volume":"33","author":"Tramontano","year":"2022","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2147\/DMSO.S342505","article-title":"Associations Between GGT\/HDL and MAFLD: A Cross-Sectional Study","volume":"15","author":"Xing","year":"2022","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113937","DOI":"10.1016\/j.intimp.2024.113937","article-title":"Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice","volume":"147","author":"Hu","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Liu, Q.K. (2024). Mechanisms of action and therapeutic applications of GLP-1 and dual GIP\/GLP-1 receptor agonists. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1431292"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:53:31Z","timestamp":1762865611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":57,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["genes16111377"],"URL":"https:\/\/doi.org\/10.3390\/genes16111377","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]}}}