The relationship of serum bilirubin level with histopathological parameters in patients with nonalcoholic fatty liver disease

Year 2023, , 91 - 96, 29.07.2023

Ali Kırık , Cemal Nuri Ercin , Hasan Gürel , Ali Fuat Çiçek Ali Cem Yekdeş , Sultan Türel , Serkan Tapan Teoman Doğru

https://doi.org/10.56016/dahudermj.1326075

Abstract

Objectives: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease and is known as a part of metabolic syndrome (MetS), and the role of bilirubin in the pathogenesis of NAFLD is unclear. This study aimed to evaluate the relationship between bilirubin levels and histopathological findings in patients with NAFLD having no confounding factors such as morbid obesity, diabetes mellitus (DM), and hypertension.
Methods: A retrospective analysis of clinical and laboratory data of patients with biopsy-proven NAFLD was performed. The relationship between the bilirubin levels and histopathologic findings was evaluated.
Results: The subjects in the nonalcoholic steatohepatitis (NASH) group had greater AST (p < 0.001) and ALT (p < 0.001) levels than the non-NASH group. We found no difference between NASH and non-NASH groups regarding bilirubin levels. The levels of AST (p = 0.001), ALT (p = 0.011), insulin (p = 0.029), and HOMA-IR index (p = 0.027) were higher in fibrosis group comparing non-fibrosis group. However, bilirubin levels were not different comparing the fibrosis and non-fibrosis group. We couldn’t find any relation between bilirubin levels and other parameters in correlation analysis.
Conclusion: We couldn’t find any relation between the bilirubin levels and histopathological findings of the patient with NAFLD having no confounding factors such as morbid obesity, DM, and hypertension. The difference, shown in the other studies, may be the effect of other diseases related to MetS.

Keywords

NAFLD, NASH, fibrosis, bilirubin

References

• Fang YL, Chen H, Wang CL, Liang L. Pathogenesis of non-alcoholic fatty liver disease in chil-dren and adolescence: From "two hit theory" to "multiple hit model". World J Gastroenterol. 2018 ;24(27):2974-2983.
• Sonmez A, Dogru T, Ercin CN, Genc H, Celebi G, Gurel H, et al. Betatrophin Levels Are Re-lated to the Early Histological Findings in Nonalcoholic Fatty Liver Disease. Metabolites. 2021;11(7):425.
• Oni ET, Agatston AS, Blaha MJ, Fialkow J, Cury R, Sposito A, et al. A systematic review: burden and severity of subclinica lcardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013; 230(2):258-267.
• Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fat-ty liver disease. N Engl J Med. 2010; 363(14):1341-1350.
• Dogru T, Kirik A, Gurel H, Rizvi AA, Rizzo M, Sonmez A. The Evolving Role of Fetuin-A in Nonalcoholic Fatty Liver Disease: An Overview from Liver to the Heart. Int J Mol Sci. 2021;22(12):6627.
• Pacifico L, Chiesa C, Anania C, Merulis AD, Osborn JF, Romaggioli S, et al. Nonalcoholic fatty liver disease and the heart in children and adolescents. World J Gastroenterol 2014; 20(27):9055–9071.
• European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64(6):1388-1402.
• Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology 2014; 146(7):1625-1638.
• DiNicolantonio JJ, McCarty MF, O'Keefe JH. Antioxidant bilirubin works in multiple ways to reduce risk for obesity and its health complications. Open Heart. 2018;5(2):e000914.
• Neuzil J, Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994; 269(24):16712-16719.
• Ndisang JF, Jadhav A. Up-regulating the hemeoxygenase system enhances insulin sensitivity and improves glucose metabolism in insulin-resistant diabetes in Goto-Kakizakirats. Endocrinol 2009; 150(6):2627-2636.
• Lin LY, Kuo HK, Hwang JJ, Lai LP, Chiang FT, Tseng CD, et al. Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 2009; 203(2):563-568.
• Jain V, Ghosh RK, Bandyopadhyay D, Kondapaneni M, Mondal S, Hajra A, et al. Serum Bili-rubin and Coronary Artery Disease: Intricate Relationship, Pathophysiology, and Recent Evi-dence. Curr Probl Cardiol. 2021;46(3):100431.
• Perlstein TS, Pande RL, Beckman JA, Creager MA. Serum total bilirubin level and prevalent lower-extremity peripheral arterial disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. Arterioscler Thromb Vasc Biol 2008; 28(1):166-172.
• Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18(6):499-502.
• Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeosta-sis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23(1):57-63.
• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Nonalco-holic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41(6):1313-1321.
• Brunt EM. Nonalcoholic fatty liver disease: what the pathologist can tell the clinician. Dig Dis 2012; 30(1):61-68.
• Takei R, Inoue T, Sonoda N, Kohjima M, Okamoto M, Sakamoto R, et al. Bilirubin reduces visceral obesity and insulin resistance by suppression of inflammatory cytokines. PLoS One. 2019;14(10):e0223302.
• Leal EC, Carvalho E. Heme Oxygenase-1 as Therapeutic Target for Diabetic Foot Ulcers. Int J Mol Sci. 2022 Oct 10;23(19):12043.
• Kwak MS, Kim D, Chung GE, Kang SJ, Park MJ, Kim YJ, et al. Serum bilirubin levels are in-versely associated with nonalcoholic fatty liver disease. Clinical and Molecular Hepatology 2012; 18(4):383-390.
• Chang Y, Ryu S, Zhang Y, Son HJ, Kim JY, Cho J, et al. A cohort study of serum bilirubin levels and incident non-alcoholic fatty liver disease in middle aged korean workers. PLoS ONE 2012; 7(5):e37241.
• Tian J, Zhong R, Liu C, Tang Y, Gong J, Chang J, et al. Association between bilirubin and risk of non-alcoholic fatty liver disease based on a prospective cohort study. Sci Rep 2016; 6(1):31006.
• Hjelkrem M, Morales A, Williams CD, Harrison SA. Unconjugated hyperbilirubinemia is in-versely associated with non-alcoholic steatohepatitis (NASH). Aliment Pharmacol Ther 2012; 35(12):1416-1423.
• Salomone F, Volti GL, Rosso C, Grosso G, Bugianesi E. Unconjugated bilirubin, a potent en-dogenous antioxidant, is decreased in patients with non-alcoholic steatohepatitis and advanced fibrosis. J Gastroenterol Hepatol 2013; 28(7):1202-1208.