Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

Abstract

Objective

Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.

Methods

Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.

Results

The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44–0.67) versus 0.44 (0.34–0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015–1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059–1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008–1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045–1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.

Conclusion

The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

References

[1] YounossiZM, KoenigAB, AbdelatifD, et al.. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016, 64(1): 73-84

[2] YounossiZM, StepanovaM, YounossiY, et al.. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut, 2020, 69(3): 564-568

[3] AndersonEL, HoweLD, JonesHE, et al.. The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS One, 2015, 10(10): e0140908

[4] DraijerL, BenningaM, KootB. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment. Expert Rev Gastroenterol Hepatol, 2019, 13(5): 447-461

[5] CaussyC, ReederSB, SirlinCB, et al.. Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials. Hepatology, 2018, 68(2): 763-772

[6] BuzzettiE, PinzaniM, TsochatzisEA. The multiple-hit pathogenesis of nonalcoholic fatty liver disease (NAFLD). Metabolism, 2016, 65(8): 1038-1048

[7] FarzanegiP, DanaA, EbrahimpoorZ, et al.. Mechanisms of beneficial effects of exercise training on nonalcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci, 2019, 19(7): 994-1003

[8] WongVW, AdamsLA, de LédinghenV, et al.. Noninvasive biomarkers in NAFLD and NASH - current progress and future promise. Nat Rev Gastroenterol Hepatol, 2018, 15(8): 461-478

[9] ShiC, PamerEG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol, 2011, 11(11): 762-774

[10] GanjaliS, MomtaziAA, BanachM, et al.. HDL abnormalities in familial hypercholesterolemia: Focus on biological functions. Progr Lipid Res, 2017, 67: 16-26

[11] UsluAU, SekinY, TarhanG, et al.. Evaluation of Monocyte to High-Density Lipoprotein Cholesterol Ratio in the Presence and Severity of Metabolic Syndrome. Clin Appl Thromb Hemost, 2018, 24(5): 828-833

[12] KatipogluZ, MirzaE, OltuluR, et al.. May Monocyte/HDL Cholesterol Ratio (MHR) and Neutrophil/Lymphocyte Ratio (NLR) Be an Indicator of Inflammation and Oxidative Stress in Patients with Keratoconus?. Ocul Immunol Inflamm, 2020, 28(4): 632-636

[13] HerkilogluD, GokceS. Correlation of monocyte/HDL ratio (MHR) with inflammatory parameters in obese patients diagnosed with polycystic ovary syndrome. Ginekol Lol, 2021, 92(8): 537-543

[14] De MatteisC, CrudeleL, CarielloM, et al.. Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects. Nutrients, 2022, 14(2): 347

[15] LiH, JiCY, ZongXN, et al.. Body mass index growth curves for Chinese children and adolescents aged 0 to 18 years. Zhonghua er ke za zhi (Chinese), 2009, 47(7): 493-498

[16] FanJG, WeiL, ZhuangH. Guidelines of prevention and treatment of nonalcoholic fatty liver disease (2018, China). J Digest Dis, 2019, 20(4): 163-173

[17] WallaceTM, LevyJC, MatthewsDR. Use and abuse of HOMA modeling. Diabetes Care, 2004, 27(6): 1487-1495

[18] MurphyAJ, WoollardKJ, HoangA, et al.. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol, 2008, 28(11): 2071-2077

[19] KundiH, GokM, KiziltuncE, et al.. Relation Between Monocyte to High-Density Lipoprotein Cholesterol Ratio With Presence and Severity of Isolated Coronary Artery Ectasia. Am J Cardiol, 2015, 116(11): 1685-1689

[20] AçıkgözSK, AçıkgözE, ŞensoyB, et al.. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in ST-segment elevation myocardial infarction. Cardiol J, 2016, 23(5): 505-512

[21] VlacilAK, SchuettJ, SchiefferB, et al.. Variety matters: Diverse functions of monocyte subtypes in vascular inflammation and atherogenesis. Vasc Pharmacol, 2019, 113: 9-19

[22] Lee-RueckertM, LappalainenJ, KovanenPT, et al.. Lipid-Laden Macrophages and Inflammation in Atherosclerosis and Cancer: An Integrative View. Front Cardiovasc Med, 2022, 9: 777822

[23] van der HeideD, WeiskirchenR, BansalR. Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases. Front Immunol, 2019, 10: 2852

[24] ClémentS, Juge-AubryC, SgroiA, et al.. Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes. Hepatology, 2008, 48(3): 799-807

[25] NegrinKA, Roth FlachRJ, DiStefanoMT, et al.. IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. PloS One, 2014, 9(9): e107265

[26] KarlmarkKR, WeiskirchenR, ZimmermannHW, et al.. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology, 2009, 50(1): 261-274

[27] GanjaliS, GottoAMJr, RuscicaM, et al.. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol, 2018, 233(12): 9237-9246

[28] FriedmanSL, Neuschwander-TetriBA, RinellaM, et al.. Mechanisms of NAFLD development and therapeutic strategies. Nat Med, 2018, 24(7): 908-922

[29] PowellEE, WongVW, RinellaM. Nonalcoholic fatty liver disease. Lancet, 2021, 397(10290): 2212-2224

[30] ShaunakM, ByrneCD, DavisN, et al.. Nonalcoholic fatty liver disease and childhood obesity. Arch Dis Child, 2021, 106(1): 3-8

[31] GuilhermeA, VirbasiusJV, PuriV, et al.. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol, 2008, 9(5): 367-377

[32] CusiK. Role of insulin resistance and lipotoxicity in nonalcoholic steatohepatitis. Clin Liver Dis, 2009, 13(4): 545-563

[33] KimD, TourosA, KimWR. Nonalcoholic Fatty Liver Disease and Metabolic Syndrome. Clin Liv Dis, 2018, 22(1): 133-140

[34] HuangH, WangQ, ShiX, et al.. Association between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study. Mediators Inflamm, 2021, 2021: 6642246

[35] WangL, DongJ, XuM, et al.. Association Between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Risk of Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study. Front Med, 2022, 9: 898931