Changes in the Dynamic Trajectory of Remnant Cholesterol Affect the Occurrence of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting approximately 20–25 % of the global adult population [ [1] Younossi Z.M. Koenig A.B. Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64: 73-84https://doi.org/10.1002/hep.28431 Crossref PubMed Scopus (6807) Google Scholar ]. Epidemiological evidence showed that, in addition to overweight and obesity, remnant cholesterol (RC) is the most important modifiable risk factor for the onset of NAFLD, and it has been confirmed to be a pathogenic factor in several studies [ [2] Gaggini M. Morelli M. Buzzigoli E. et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 2013; 5: 1544-1560https://doi.org/10.3390/nu5051544 Crossref PubMed Scopus (616) Google Scholar , [3] Katsiki N. Mikhailidis D.P. Mantzoros C.S Non-alcoholic fatty liver disease and dyslipidemia: an update. Metabolism. 2016; 65: 1109-1123https://doi.org/10.1016/j.metabol.2016.05.003 Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar ]. RC can be described as the remaining fraction of cholesterol in addition to high-density lipoprotein cholesterol (HDL-C) and high-density lipoprotein cholesterol (LDL-C) [ [4] Varbo A. Nordestgaard B.G Remnant lipoproteins. Curr Opin Lipidol. 2017; 28: 300-307https://doi.org/10.1097/MOL.0000000000000429 Crossref Scopus (72) Google Scholar ]. When excess RC is present in the plasma, it easily penetrates the arterial wall and becomes foam cells, causing low-grade inflammation and contributing to plaque formation, leading to an aberrant lipid metabolism profile [ [5] Baratta F. Cocomello N. Coronati M. et al. Cholesterol remnants, triglyceride-rich lipoproteins and cardiovascular risk. Int J Mol Sci. 2023; 24https://doi.org/10.3390/ijms24054268 Crossref Scopus (6) Google Scholar ]. Disturbances in lipid metabolism in the liver, combined with a prolonged chronic inflammatory environment, lead to fatty degeneration of liver tissue. These findings support the idea that RC leads to NAFLD [ [6] Cheng Y. Zhang Q. Li H. et al. Remnant cholesterol, stronger than triglycerides, is associated with incident non-alcoholic fatty liver disease. Front Endocrinol (Lausanne). 2023; 141098078https://doi.org/10.3389/fendo.2023.1098078 Crossref Scopus (2) Google Scholar ], can cause metabolic abnormalities and vascular damage, and participates in the occurrence of cardiovascular events [ [7] Varbo A. Benn M. Tybjaerg-Hansen A. et al. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013; 128: 1298-1309https://doi.org/10.1161/CIRCULATIONAHA.113.003008 Crossref PubMed Scopus (361) Google Scholar , [8] Langsted A. Madsen C.M. Nordestgaard B.G Contribution of remnant cholesterol to cardiovascular risk. J Intern Med. 2020; 288: 116-127https://doi.org/10.1111/joim.13059 Crossref PubMed Scopus (79) Google Scholar ]. Unfortunately, there are no approved pharmacological treatments for patients with NAFLD who have cardiovascular disease [ [9] Mellemkjaer A. Kjaer M.B. Haldrup D. et al. Management of cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med. 2023; https://doi.org/10.1016/j.ejim.2023.11.012 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. The changes in lipids and RC in the population are dynamic, and further investigation is still needed to fully understand the relationship between the dynamic progression of RC levels and the development of NAFLD. The primary purpose of this cohort study that spanned five years was to investigate the development of RC trajectories in the population and the relationship between RC and NAFLD, thereby further confirming the association between RC and NAFLD development. The importance of this study is that it showed the influential impact of the dynamic development of RC on new-onset NAFLD from 2017 to 2022.