Neopterin as an Inflammatory Biomarker in Patients with Non-alcoholic Fatty Liver Disease


  • Rawa Ratha Department of Clinical Pharmacy, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Vian Ahmed Wasta-Esmail Department of Clinical Pharmacy, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Fenk Bakir Maarouf Department of Biochemistry, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Hemn Abdalla Omer Department of Microbiology, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Marwan Al-Nimer Department of Pharmacology and Toxicology, Hawler Medical University, Erbil, Kurdistan Region, Iraq. Author
  • Mohammed Omer Mohammed Department of Medicine, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. Author



Nonalcoholic fatty liver disease, Pro.inflammatory cytokines, Neopterin, Cross.sectional study


Background: Early diagnosis of non-alcoholic fatty liver diseases (NAFLD) through detection of a new biomarker is crucial to prevent disease deterioration.

Aim: To evaluate the serum level of neopterin in NAFLD patients and to demonstrate its role as an early biomarker of NAFLD.

Methodology: This is an observational, cross-sectional study that conducted on 71 newly diagnosed NAFLD patients and 60 healthy individuals as a control group. Liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and uric acid were determined. The serum level of neopterin was measured by ELISA and WBC differential count by a Coulter counter analyzer. Erythrocyte sedimentation rate (ESR) was determined by Wintrobe’s method.

Results: NAFLD patients had a significantly higher BMI, waist circumference, and body weight compared to control, also their blood pressure was significantly higher. The serum level of ALT, AST, and uric acid were significantly higher in NAFLD patients than the control. There is non-significant difference between NAFLD patients and controls regarding ESR, lymphocytes and granulocytes, while monocytes and neopterin values were significantly higher among NAFLD patients.

Conclusions: Serum neopterin level can be a predictor inflammatory marker in NAFLD patients. Clinical Pharmacists as part of healthcare professionals can support NAFLD patients by educating them on lifestyle modification if the disease is diagnosed early before reaching a critical stage.


Sumida Y, Yoshikawa T, Tanaka S, Taketani H, Kanemasa K, Nishimura T, et al. The ‘donations for decreased ALT (D4D)’ prosocial behaviour incentive scheme for NAFLD patients. J Public Health (Oxf) 2014; 36: 629- 634. [2] Pulzi FB, Cisternas R, Melo MR, Ribeiro CM, Malheiros CA, Salles JE. A new clinical score to diagnose nonalcoholic steatohepatitis in obese patients. Diabetol Metab Syndr 2011; 3: 3. [3] Tevar AD, Clarke C, Wang J, Rudich SM, Woodle ES, Lentsch AB, Edwards ML. Clinical review of nonalcoholic steatohepatitis in liver surgery and transplantation. J Am Coll Surg 2010; 210: 515-526. [4] De Hewavisenthi SJ, Dassanayaka AS, De Silva HJ. Clinical, biochemical, and histological characteristics of a Sri Lankan population of non-alcoholic steatohepatitis (NASH) patients. Ceylon Med J 2005; 50: 113-116. JZS-A Volume 24, Issue 1, June 2022 100 [5] Wilson S, Chalasani N. Noninvasive markers of advanced histology in nonalcoholic fatty liver disease: are we there yet? Gastroenterology 2007; 133: 1377-1378. [6] Scheja L, Heeren J. Metabolic interplay between white, beige, brown adipocytes and the liver. J Hepatol 2016; 64:1176–1186. [7] Wieckowska A, Papouchado BG, Li Z, et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103:1372–1379. [8] Fon Tracer K, Kuzman D, Seliskar M, Pompon D, Rozman D. TNF-alpha interferes with lipid homeostasis and activates acute and proatherogenic processes. Physiol Genomics 2007; 31: 216-227. [9] Feingold KR, Soued M, Serio MK, Adi S, Moser AH, Grunfeld C. The effect of diet on tumour necrosis factor stimulation of hepatic lipogenesis. Metabolism 1990; 39: 623-632. [10] Das SK, Balakrishnan V. Role of cytokines in the pathogenesis of non-alcoholic Fatty liver disease. Indian J Clin Biochem 2011; 26: 202-209. [11] Chan JL, Wong SL, Mantzoros CS. Pharmacokinetics of subcutaneous recombinant methionyl human leptin administration in healthy subjects in the fed and fasting states regulation by gender and adiposity. Clin Pharmacokinet 2008; 47: 753-764. [12] Tilg H. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis 2010; 28: 179-185. [13] Sucher R, Schroecksnadel K, Weiss G, Margreiter R, Fuchs D, Brandacher G. Neopterin, a prognostic marker in human malignancies. Cancer Lett 2010; 287(1):13–22. [14] Neurauter G, Schrocksnadel K, Scholl-Burgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, et al. Chronic immune stimulation correlates with reduced phenylalanine turnover. Curr Drug Metab 2008; 9(7):622– 627. [15] Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K, et al. Pteridine biosynthesis in human endothelial cells. Impact on the nitric oxide-mediated formation of cyclic GMP, J. Biol. Chem. 1993; 268: 1842–1846. [16] D'agostino LE, Ventimiglia F, Verna JA, Colina Ade L, Aguirre Y, Arturi A, et al. Correlation between DAS.28 and neopterin as a biochemical marker of immune system activation in early rheumatoid arthritis, Autoimmunity 2013; 46: 44–49. [17] Viaccoz A, Ducray F, Tholance Y, Barcelos GK, Thomas-Maisonneuve L, Ghesquières H, et al. CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma, Neuro-Oncology 2015;17: 1497– 1503. [18] Bansil S, Mithen FA, Singhal BS, Cook SD, Rohowsky-Kochan C. Elevated neopterin levels in Guillain-Barré syndrome. Further evidence of immune activation, Arch. Neurol. 1992; 49: 1277–1280. [19] Ipekci SH, Kebapcilar AG, Yilmaz SA, Ilhan TT, Pekin AT, Abusoglu S, et al. Serum levels of neopterin in gestational diabetes mellitus: the relationship with Apgar scores, Arch Gynecol Obstet. 2015; 292: 103–109. [20] Marwan A, Rawa R, Taha M. Utility of Tetrahydrobiopterin Pathway in the Assessment of Diabetic Foot Ulcer: Significant and Complex Interrelations. Journal of Diabetes Research, Volume 2019, Article ID 3426878, 7 pages. [21] Daito K, Suou T, Kawasaki H. Clinical significance of serum and urinary neopterin levels in patients with various liver diseases. Am J Gastroenterol 1992; 87: 471–476. [22] Ahmet U, Abdurrahman K, Ugur M, Nuri E, Yildirim K, Bulent D, et al. Serum neopterin levels in patients with non-alcoholic steatohepatitis. Hepatology Research 2008; 38: 904–908. [23] Kaneki M, Shimizu N, Yamada D. Nitrosative stress and pathogenesis of insulin resistance. Antioxid Redox Signal. 2007; 9: 319-329. [24] Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010;5: 145-171. [25] Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120:1183-1192. JZS-A Volume 24, Issue 1, June 2022 101 [26] Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. HEPATOLOGY 2010;51: 679-689. [27] Sun K, Kusminski CM, Scherer PE. Adipose tissue remodelling and obesity. J Clin Invest 2011; 121:2094– 2101. [28] Moschen AR, Molnar C, Geiger S, et al. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor-alpha expression. Gut 2010; 59:1259–1264. [29] Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92:1023–1033. [30] Stojsavljevic S, Gomercic Palcic M, Virovic Jukic L. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of the nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20:18070– 18091. [31] Stoner L, Lucero AA, Palmer BR. Inflammatory biomarkers for predicting cardiovascular disease. Clin Biochem 2013; 46:1353–1371. [32] Hossain N, Afendy A, Stepanova M, Nader F, Srishord M, Rafiq N, et al. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1224-1229, 1229e1-e2. [33] Wilfred de Alwis NM, Day CP. Genetics of alcoholic liver disease and nonalcoholic fatty liver disease. Semin Liver Dis 2007; 27: 44-54. [34] Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006; 44: 466-471. [35] Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44-52. [36] Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007; 102: 399-408. [37] Sirota JC, McFann K, Targher G, Johnson RJ, Chonchol M, Jalal DI. Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: liver ultrasound data from the National Health and Nutrition Examination Survey. Metabolism 2013; 62(3): 392–399. [38] Yong-Jae Lee, Hye-Ree Lee, Jung-Hyun Lee, Youn-Ho Shin, and Jae-Yong Shim. Association between serum uric acid and non-alcoholic fatty liver disease in Korean adults. Clin Chem Lab Med 2010;48(2):175–180. [39] Park SH, Kim BI, Yun JW. Insulin resistance and C-reactive protein as independent risk factors for nonalcoholic fatty liver disease in non-obese Asian men. Journal of Gastroenterology and Hepatology 2004; 19(6): 694–698. [40] Hack-Lyoung K, Goh EC, In YP, Jin MC, Se-Min H, Jeong-Hoon L, et al. Elevated Peripheral Blood Monocyte Fraction in Nonalcoholic Fatty Liver Disease. Tohoku J Exp Med 2011;223: 227-233. [41] Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of non-alcoholic fatty liver disease. QJM 2010; 103: 71-83. [42] Byrne CD. Fatty liver: role of inflammation and fatty acid nutrition. Prostaglandins Leukot. Essent. Fatty Acids 2010; 82: 265-271. [43] Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010; 5: 145-171. [44] Siebler J, Galle PR, Weber MM. The gut-liver-axis: endotoxemia, inflammation, insulin resistance and NASH. J Hepatol 2008; 48: 1032-1034. [45] Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 27: 412-421. [46] Abiru S, Migita K, Maeda Y, Daikoku M, Ito M, Ohata K, Nagaoka S, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int 2006; 26: 39-45



How to Cite

Neopterin as an Inflammatory Biomarker in Patients with Non-alcoholic Fatty Liver Disease. (2022). Journal of Zankoy Sulaimani, 24(1), 95-101.

Most read articles by the same author(s)