High Remnant Cholesterol Increased the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) or Non-Alcoholic Fatty Liver Disease (NAFLD)
A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.15605/jafes.041.01.5159Keywords:
remnant cholesterol, insulin resistance, MAFLD, NAFLDAbstract
Background. MAFLD is currently acknowledged as the most common chronic liver disease and is strongly associated with obesity, metabolic dysregulation and diabetes. MAFLD is defined by the accumulation of lipids within the liver due to impaired lipid metabolism.
Objective. The objective of this study is to assess the association between increased remnant cholesterol levels and the likelihood of developing MAFLD or NAFLD.
Methodology. A systematic review and meta-analysis were performed in accordance with PRISMA recommendations. Databases such as the Cochrane Library and PubMed were queried for relevant material through March 21, 2025, using specific keywords related to remnant cholesterol and fatty liver disorders. The inclusion criteria concentrated on research investigating the influence of remnant cholesterol on the incidence of NAFLD/MAFLD. Data extraction and quality evaluation were conducted utilizing the JBI Critical Appraisal Checklist for Cohort Studies and ROBINS-I instruments.
Results. Six studies were eventually included in our systematic review, including cross-sectional studies with a total of 45,821participants. The meta-analysis, conducted with Review Manager version 5.4, demonstrated a significant association between elevated remnant cholesterol levels and an increased risk of NAFLD/MAFLD, yielding a relative risk (RR) of 3.18 (95% CI 1.89-5.37; p <0.00001; I2 = 99%). This indicates a robust link between remnant cholesterol and the prevalence of various hepatic disorders.
Conclusion. Remnant cholesterol is associated with MAFLD or NAFLD. Increased remnant cholesterol is a risk factor for MAFLD or NAFLD.
Downloads
References
Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic Proceedings. 1980;55(7):434-8. https://pubmed.ncbi.nlm.nih.gov/7382552 DOI: https://doi.org/10.1016/S0025-6196(24)00530-5
Eslam M, Sanyal AJ, George J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158(7):1999-2014.e1. https://pubmed.ncbi.nlm.nih.gov/32044314 https://doi.org/10.1053/j.gastro.2019.11.312 DOI: https://doi.org/10.1053/j.gastro.2019.11.312
Fouad Y, Waked I, Bollipo S, et al. What’s in a name? Renaming ‘NAFLD’ to ‘MAFLD’. Liver Int. 2020;40(6):1254-61. https://pubmed.ncbi.nlm.nih.gov/32301554 https://doi.org/10.1111/liv.14478. DOI: https://doi.org/10.1111/liv.14478
Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202–9. https://pubmed.ncbi.nlm.nih.gov/32278004 https://doi.org/10.1016/j.jhep.2020.03.039
Wang X, Wu S, Yuan X, et al. Metabolic Dysfunction-associated Fatty Liver Disease and mortality among Chinese adults: A prospective cohort study. J Clin Endocrinol Metab. 2022;107(2):e745-55. https://pubmed.ncbi.nlm.nih.gov/34467980 https://doi.org/10.1210/clinem/dgab644. DOI: https://doi.org/10.1210/clinem/dgab644
Kim D, Konyn P, Sandhu KK, et al. Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States. J Hepatol. 2021;75(6):1284-91. https://pubmed.ncbi.nlm.nih.gov/34380057 https://doi.org/10.1016/j.jhep.2021.07.035. DOI: https://doi.org/10.1016/j.jhep.2021.07.035
Eren F, Kaya E, Yilmaz Y. Accuracy of fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores in metabolic (dysfunction) associated fatty liver disease according to body mass index: Failure in the prediction of advanced fibrosis in lean and morbidly obese individuals. Eur J Gastroenterol Hepatol. 2022;34(1):98-103. https://pubmed.ncbi.nlm.nih.gov/32976186 https://doi.org/10.1097/MEG.0000000000001946. DOI: https://doi.org/10.1097/MEG.0000000000001946
Lin S, Huang J, Wang M, et al. Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int. 2020;40(9):2082-9. https://pubmed.ncbi.nlm.nih.gov/32478487 https://doi.org/10.1111/liv.14548. DOI: https://doi.org/10.1111/liv.14548
Liang Y, Chen H, Liu Y, et al. Association of MAFLD with diabetes, chronic kidney disease, and cardiovascular disease: A 4.6-year cohort study in China. J Clin Endocrinol Metab. 2022;107(1):88-97. https://pubmed.ncbi.nlm.nih.gov/34508601 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684479 https://doi.org/10.1210/clinem/dgab641. DOI: https://doi.org/10.1210/clinem/dgab641
Pan L, Huang P, Xie X, et al. Metabolic associated fatty liver disease increases the severity of COVID-19: A meta-analysis. Dig Liver Dis. 2021;53(2):153-7. https://pubmed.ncbi.nlm.nih.gov/33011088 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498251 https://doi.org/10.1016/j.dld.2020.09.007. DOI: https://doi.org/10.1016/j.dld.2020.09.007
Fouad Y, Gomaa A, Semida N, et al. Change from NAFLD to MAFLD increases the awareness of fatty liver disease in primary care physicians and specialists. J Hepatol. 2021;74(5):1254-6. https://pubmed.ncbi.nlm.nih.gov/33582129 https://doi.org/10.1016/j.jhep.2020.12.035. DOI: https://doi.org/10.1016/j.jhep.2020.12.035
Pan Z, Fan JG, Eslam M. An update on drug development for the treatment of metabolic (dysfunction) associated fatty liver disease: Progress and opportunities. Curr Opin Pharmacol. 2021;60:170-6. https://pubmed.ncbi.nlm.nih.gov/34455284 https://doi.org/10.1016/j.coph.2021.07.007. DOI: https://doi.org/10.1016/j.coph.2021.07.007
Eslam M, George J. MAFLD: Now is the time to capitalize on the momentum. J Hepatol. 2021;74(5):1262-3. https://pubmed.ncbi.nlm.nih.gov/33587953 https://doi.org/10.1016/j.jhep.2021.02.002. DOI: https://doi.org/10.1016/j.jhep.2021.02.002
Mak LY, Yuen MF, Seto WK. Letter regarding "A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement". J Hepatol. 2020;73(6):1573-4. https://pubmed.ncbi.nlm.nih.gov/32951910 https://doi.org/10.1016/j.jhep.2020.07.008. DOI: https://doi.org/10.1016/j.jhep.2020.07.008
van Kleef LA, Choi HSJ, Brouwer WP, et al. Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B. JHEP Rep. 2021;3(5):100350. https://pubmed.ncbi.nlm.nih.gov/34557660 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446794 https://doi.org/10.1016/j.jhepr.2021.100350. DOI: https://doi.org/10.1016/j.jhepr.2021.100350
Younossi ZM, Rinella ME, Sanyal AJ, et al. From NAFLD to MAFLD: Implications of a premature change in terminology. Hepatology. 2021;73(3):1194-8. https://pubmed.ncbi.nlm.nih.gov/32544255 https://doi.org/10.1002/hep.31420. DOI: https://doi.org/10.1002/hep.31420
Tsutsumi T, Kawaguchi T, Nakano D, et al. Atherosclerotic cardiovascular disease in non-metabolic nonalcoholic fatty liver disease. Hepatol Res. 2022;52(3):317-9. https://pubmed.ncbi.nlm.nih.gov/35229393 https://doi.org/10.1111/hepr.13738. DOI: https://doi.org/10.1111/hepr.13738
Ciardullo S, Carbone M, Invernizzi P, et al. Impact of the new definition of metabolic dysfunction-associated fatty liver disease on detection of significant liver fibrosis in US adolescents. Hepatol Commun. 2022;6(8):2070-8. https://pubmed.ncbi.nlm.nih.gov/35470984 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315136 https://doi.org/10.1002/hep4.1969. DOI: https://doi.org/10.1002/hep4.1969
Eslam M, Ahmed A, Després JP, et al. Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases. Lancet Gastroenterol Hepatol. 2021;6(9):743-53. https://pubmed.ncbi.nlm.nih.gov/34265276 https://doi.org/10.1016/S2468-1253(21)00132-1. DOI: https://doi.org/10.1016/S2468-1253(21)00132-1
Méndez-Sánchez N, Díaz-Orozco L, Córdova-Gallardo J. Redefinition of fatty liver disease from NAFLD to MAFLD raised disease awareness: Mexican experience. J Hepatol. 2021;75(1):221-2. https://pubmed.ncbi.nlm.nih.gov/33892008 https://doi.org/10.1016/j.jhep.2021.04.021. DOI: https://doi.org/10.1016/j.jhep.2021.04.021
Eslam M, Ratziu V, George J. Yet more evidence that MAFLD is more than a name change. J Hepatol. 2021;74(4):977-9. https://pubmed.ncbi.nlm.nih.gov/33453331 https://doi.org/10.1016/j.jhep.2020.12.025. DOI: https://doi.org/10.1016/j.jhep.2020.12.025
Ayada I, van Kleef LA, Alferink LJM, et al. Systematically comparing epidemiological and clinical features of MAFLD and NAFLD by meta-analysis: Focusing on the non-overlap groups. Liver Int. 2022;42(2):277-87. https://pubmed.ncbi.nlm.nih.gov/34953098 https://doi.org/10.1111/liv.15139. DOI: https://doi.org/10.1111/liv.15139
Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-9. https://pubmed.ncbi.nlm.nih.gov/32278004 https://doi.org/10.1016/j.jhep.2020.03.039. DOI: https://doi.org/10.1016/j.jhep.2020.07.045
Crane H, Gofton C, Sharma A, et al. MAFLD: An optimal framework for understanding liver cancer phenotypes. J Gastroenterol. 2023;58(10):947-64. https://pubmed.ncbi.nlm.nih.gov/37470858 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522746 https://doi.org/10.1007/s00535-023-02021-7. DOI: https://doi.org/10.1007/s00535-023-02021-7
Nassir F. NAFLD: Mechanisms, treatments, and biomarkers. Biomolecules. 2022;12(6):824. https://pubmed.ncbi.nlm.nih.gov/35740949 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221336 https://doi.org/10.3390/biom12060824. DOI: https://doi.org/10.3390/biom12060824
Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223-38. https://pubmed.ncbi.nlm.nih.gov/33349658 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016738 https://doi.org/10.1038/s41575-020-00381-6. DOI: https://doi.org/10.1038/s41575-020-00381-6
Younossi ZM, Stepanova M, Ong J, et al. Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19(3):580-9.e5. https://pubmed.ncbi.nlm.nih.gov/32531342 https://doi.org/10.1016/j.cgh.2020.05.064. DOI: https://doi.org/10.1016/j.cgh.2020.05.064
Mantovani A, Dalbeni A. Treatments for NAFLD: State of the art. Int J Mol Sci. 2021;22(5):2350. https://pubmed.ncbi.nlm.nih.gov/33652942 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956331 https://doi.org/10.3390/ijms22052350. DOI: https://doi.org/10.3390/ijms22052350
Badmus OO, Hillhouse SA, Anderson CD, et al. Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): Functional analysis of lipid metabolism pathways. Clin Sci (Lond). 2022;136(18):1347-66. https://pubmed.ncbi.nlm.nih.gov/36148775 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508552 https://doi.org/10.1042/CS20220572. DOI: https://doi.org/10.1042/CS20220572
Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: An update. Metabolism. 2016;65(8):1109-23. https://pubmed.ncbi.nlm.nih.gov/27237577 https://doi.org/10.1016/j.metabol.2016.05.003. DOI: https://doi.org/10.1016/j.metabol.2016.05.003
Stürzebecher PE, Katzmann JL, Laufs U. What is “remnant cholesterol”? Eur Heart J. 2023;44(16):1446-8. https://pubmed.ncbi.nlm.nih.gov/36650915 https://doi.org/10.1093/eurheartj/ehac783. DOI: https://doi.org/10.1093/eurheartj/ehac783
Zou Y, Lan J, Zhong Y, et al. Association of remnant cholesterol with nonalcoholic fatty liver disease: A general population-based study. Lipids Health Dis. 2021;20(1):139. https://pubmed.ncbi.nlm.nih.gov/34657611 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520640 https://doi.org/10.1186/s12944-021-01573-y. DOI: https://doi.org/10.1186/s12944-021-01573-y
Quispe R, Martin SS, Michos ED, et al. Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: A primary prevention study. Eur Heart J. 2021;42(42):4324-32. https://pubmed.ncbi.nlm.nih.gov/34293083 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572557 https://doi.org/10.1093/eurheartj/ehab432. DOI: https://doi.org/10.1093/eurheartj/ehab432
Li W, Huang Z, Fang W, et al. Remnant cholesterol variability and incident ischemic stroke in the general population. Stroke. 2022;53(6):1934-41. https://pubmed.ncbi.nlm.nih.gov/35543132 https://doi.org/10.1161/STROKEAHA.121.037756. DOI: https://doi.org/10.1161/STROKEAHA.121.037756
Huang H, Guo Y, Liu Z, et al. Remnant cholesterol predicts long-term mortality of patients with metabolic dysfunction–associated fatty liver disease. J Clin Endocrinol Metab. 2022;107(8):e3295-303. https://pubmed.ncbi.nlm.nih.gov/35521833 https://doi.org/10.1210/clinem/dgac283. DOI: https://doi.org/10.1210/clinem/dgac283
Wang S, Zhang Q, Qin B. Association between remnant cholesterol and insulin resistance levels in patients with metabolic-associated fatty liver disease. Sci Rep. 2024;14(1):4596. https://pubmed.ncbi.nlm.nih.gov/38409335 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897142 https://doi.org/10.1038/s41598-024-55282-4. DOI: https://doi.org/10.1038/s41598-024-55282-4
Heeren J, Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism. Mol Metab. 2021;50:101238. https://pubmed.ncbi.nlm.nih.gov/33892169 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324684 https://doi.org/10.1016/j.molmet.2021.101238. DOI: https://doi.org/10.1016/j.molmet.2021.101238
Hu X, Liu Q, Guo X, et al. The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus. Cardiovasc Diabetol. 2022;21(1):117. https://pubmed.ncbi.nlm.nih.gov/35761281 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238255 https://doi.org/10.1186/s12933-022-01554-0. DOI: https://doi.org/10.1186/s12933-022-01554-0
Castañer O, Pintó X, Subirana I, et al. Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease. J Am Coll Cardiol. 2020;76(23):2712-24. https://pubmed.ncbi.nlm.nih.gov/33272365 https://doi.org/10.1016/j.jacc.2020.10.008. DOI: https://doi.org/10.1016/j.jacc.2020.10.008
Sakurai Y, Kubota N, Yamauchi T, et al. Role of insulin resistance in MAFLD. Int J Mol Sci. 2021;22(8):4156. https://pubmed.ncbi.nlm.nih.gov/33923817 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072900 https://doi.org/10.3390/ijms22084156. DOI: https://doi.org/10.3390/ijms22084156
Watt MJ, Miotto PM, De Nardo W, et al. The liver as an endocrine organ-linking NAFLD and insulin resistance. Endocr Rev. 2019;40(5):1367-93. https://pubmed.ncbi.nlm.nih.gov/31098621 https://doi.org/10.1210/er.2019-00034. DOI: https://doi.org/10.1210/er.2019-00034
Haas ME, Attie AD, Biddinger SB. The regulation of ApoB metabolism by insulin. Trends Endocrinol Metab. 2013;24(8):391-7. https://pubmed.ncbi.nlm.nih.gov/23721961 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810413 https://doi.org/10.1016/j.tem.2013.04.001. DOI: https://doi.org/10.1016/j.tem.2013.04.001
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(5):1544-60. https://pubmed.ncbi.nlm.nih.gov/23666091 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708335 https://doi.org/10.3390/nu5051544. DOI: https://doi.org/10.3390/nu5051544
Birkenfeld AL, Shulman GI. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology. 2014;59(2):713-23. https://pubmed.ncbi.nlm.nih.gov/23929732 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946772 https://doi.org/10.1002/hep.26672. DOI: https://doi.org/10.1002/hep.26672
Zou Y, Sheng G, Yu M, et al. The association between triglycerides and ectopic fat obesity: An inverted U-shaped curve. PLoS One. 2020;15(11):e0243068. https://pubmed.ncbi.nlm.nih.gov/33253312 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703893 https://doi.org/10.1371/journal.pone.0243068. DOI: https://doi.org/10.1371/journal.pone.0243068
Yamaguchi K, Yang L, McCall S, et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology. 2007;45(6):1366-74. https://pubmed.ncbi.nlm.nih.gov/17476695 https://doi.org/10.1002/hep.21655. DOI: https://doi.org/10.1002/hep.21655
Fon Tacer K, Rozman D. Nonalcoholic fatty liver disease: Focus on lipoprotein and lipid deregulation. J Lipids. 2011;2011:783976. https://pubmed.ncbi.nlm.nih.gov/21773052 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136146 https://doi.org/10.1155/2011/783976. DOI: https://doi.org/10.1155/2011/783976
Min HK, Kapoor A, Fuchs M, et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab. 2012;15(5):665-74. https://pubmed.ncbi.nlm.nih.gov/22560219 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361911 https://doi.org/10.1016/j.cmet.2012.04.004. DOI: https://doi.org/10.1016/j.cmet.2012.04.004
Van Rooyen DM, Larter CZ, Haigh WG, et al. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology. 2011;141(4):1393-403, 1403.e1-5. https://pubmed.ncbi.nlm.nih.gov/21703998 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186822 https://doi.org/10.1053/j.gastro.2011.06.040. DOI: https://doi.org/10.1053/j.gastro.2011.06.040
Nuño-Lámbarri N, Domínguez-Pérez M, Baulies-Domenech A, et al. Liver cholesterol overload aggravates obstructive cholestasis by inducing oxidative stress and premature death in mice. Oxid Med Cell Longev. 2016;2016:9895176. https://pubmed.ncbi.nlm.nih.gov/27635189 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011220 https://doi.org/10.1155/2016/9895176. DOI: https://doi.org/10.1155/2016/9895176
Ducheix S, Montagner A, Theodorou V, Ferrier L, Guillou H. The liver X receptor: A master regulator of the gut-liver axis and a target for non alcoholic fatty liver disease. Biochem Pharmacol. 2013;86(1):96-105. https://pubmed.ncbi.nlm.nih.gov/23542537 https://doi.org/10.1016/j.bcp.2013.03.016. DOI: https://doi.org/10.1016/j.bcp.2013.03.016
Twickler TB, Dallinga-Thie GM, Cohn JS, Chapman MJ. Elevated remnant-like particle cholesterol concentration: A characteristic feature of the atherogenic lipoprotein phenotype. Circulation. 2004;109(16):1918-25. https://pubmed.ncbi.nlm.nih.gov/15117861 https://doi.org/10.1161/01.CIR.0000125278.58527.F3. DOI: https://doi.org/10.1161/01.CIR.0000125278.58527.F3
Varbo A, Benn M, Tybjærg-Hansen A, Nordestgaard BG. 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(12):1298-309. https://pubmed.ncbi.nlm.nih.gov/23926208 https://doi.org/10.1161/CIRCULATIONAHA.113.003008. DOI: https://doi.org/10.1161/CIRCULATIONAHA.113.003008
Pastori D, Baratta F, Novo M, et al. Remnant lipoprotein cholesterol and cardiovascular and cerebrovascular events in patients with non-alcoholic fatty liver disease. J Clin Med. 2018;7(11):378. https://pubmed.ncbi.nlm.nih.gov/30360566 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262373 https://doi.org/10.3390/jcm7110378. DOI: https://doi.org/10.3390/jcm7110378
Chin J, Mori TA, Adams LA, et al. Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents. JHEP Rep. 2020;2(6):100150. https://pubmed.ncbi.nlm.nih.gov/32984791 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495103 https://doi.org/10.1016/j.jhepr.2020.100150. DOI: https://doi.org/10.1016/j.jhepr.2020.100150
Campanella A, Iacovazzi PA, Misciagna G, et al. The effect of three Mediterranean diets on remnant cholesterol and non-alcoholic fatty liver disease: A secondary analysis. Nutrients. 2020;12(6):1674. https://pubmed.ncbi.nlm.nih.gov/32512752 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352824 https://doi.org/10.3390/nu12061674. DOI: https://doi.org/10.3390/nu12061674
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;14:1098078. https://pubmed.ncbi.nlm.nih.gov/37214248 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198261 https://doi.org/10.3389/fendo.2023.1098078. DOI: https://doi.org/10.3389/fendo.2023.1098078
Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci. 2019;76(1):99-128. https://pubmed.ncbi.nlm.nih.gov/30343320 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11105781 https://doi.org/10.1007/s00018-018-2947-0. DOI: https://doi.org/10.1007/s00018-018-2947-0
Mota M, Banini BA, Cazanave SC, Sanyal AJ. Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease: A mechanistic overview. Metabolism. 2016;65(8):1049-61. https://pubmed.ncbi.nlm.nih.gov/26997538 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931958 https://doi.org/10.1016/j.metabol.2016.02.014. DOI: https://doi.org/10.1016/j.metabol.2016.02.014
Hirsova P, Ibrabim SH, Gores GJ, Malhi H. Lipotoxic lethal and sublethal stress signaling in hepatocytes: Relevance to NASH pathogenesis. J Lipid Res. 2016;57(10):1758-70. https://pubmed.ncbi.nlm.nih.gov/27049024 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036373 https://doi.org/10.1194/jlr.R066357. DOI: https://doi.org/10.1194/jlr.R066357
Cortez-Pinto H, Carneiro de Moura M, Day CP. Non-alcoholic steatohepatitis: From cell biology to clinical practice. J Hepatol. 2006;44(1):197-208. https://pubmed.ncbi.nlm.nih.gov/16274837 https://doi.org/10.1016/j.jhep.2005.09.002. DOI: https://doi.org/10.1016/j.jhep.2005.09.002
Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836-46. https://pubmed.ncbi.nlm.nih.gov/21038418 https://doi.org/10.1002/hep.24001. DOI: https://doi.org/10.1002/hep.24001
Sandesara PB, Virani SS, Fazio S, Shapiro MD. The forgotten lipids: Triglycerides, remnant cholesterol, and atherosclerotic cardiovascular disease risk. Endocr Rev. 2019;40(2):537-57. https://pubmed.ncbi.nlm.nih.gov/30312399 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416708 https://doi.org/10.1210/er.2018-00184. DOI: https://doi.org/10.1210/er.2018-00184
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Taufik Biya, Himawan Sanusi, Andi Makbul Aman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The full license text is available at: http://creativecommons.org/licenses/by-nc/3.0/legalcode.
To request permission to translate, reproduce, download, or use articles or images for commercial reuse or business purposes from the Journal of the ASEAN Federation of Endocrine Societies (JAFES), kindly complete the Permission Request for Use of Copyrighted Material Form and email jafes@asia.com or jafes.editor@gmail.com.
A written agreement will be issued to the requester once permission has been granted.
