Evaluation of the relationship between disease activity and serum bilirubin, albumin, and uric acid levels in Crohn's disease

Abstract

Objective: Oxidative stress and antioxidant deficiency play key roles in the pathogenesis of gastrointestinal damage associated with Crohn's disease (CD). Serum bilirubin, uric acid (UA) and albumin are non-enzymatic antioxidants that play a role in oxidative stress control. In this study, it was aimed to evaluate the change in serum bilirubin, UA and albumin levels due to disease activity. Material and Method: This study was designed as a single-center, cross-sectional and retrospective. The clinical and demographic data of the patients, disease activity, as well as serum albumin, UA, and bilirubin values were recorded from the hospital database. Study variables were statistically analyzed between patient and control groups based on disease activity. Results: A total of 234 people, 114 with CD and 120 with controls, were included in the study. Total bilirubin, direct bilirubin and albumin levels were found to be significantly lower in the CD than in the health control (p=0.045, p<0.001, p<0.001). There was a significant difference in total bilirubin, direct bilirubin, indirect bilirubin and albumin levels between the control group and active CD (p=0.009; p=0.001; p=0.037; p=<0.001); no significant difference with the UA level (p=0.992). There was a significant difference in direct bilirubin levels between the control group and remission CD (p=0.005); no difference in total bilirubin, indirect bilirubin, albumin, and UA levels (p=0.263; p=0.440; p=0.112; p=0.365, respectively). Conclusion: Antioxidant capacity reaches levels similar to the healthy population in patients who achieve remission with medical treatment.

Keywords

• Albumin
• Bilirubin
• Croh's disease
• Oxidative stress
• Uric acid

References

1. Wilkins T, Jarvis K, Patel J. Diagnosis and management of Crohn's disease. Am Fam Physician 2011; 84: 1365-75.
2. Yang H, Li Y, Wu W, et al. The incidence of inflammatory bowel disease in Northern China: a prospective population-based study. PloS one 2014; 9: e101296.
3. Cosnes J, Gower–Rousseau C, Seksik P, et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140: 1785-94.
4. Ananthakrishnan AN, Cheng SC, Cai T, et al. Serum inflammatory markers and risk of colorectal cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014; 12: 1342-8.
5. Jangi S, Otterbein L, Robson S. The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol 2013; 45: 2843-51.
6. Dos Santos BH, de R Almeida CM, Skare TL. Systemic Lupus Erythematosus activity and serum bilirubins. Acta Reumatol Port 2013; 38: 242-6.
7. Peng Y, Zhang L, Pan G, et al. A potential clinical usefulness of measuring serum bilirubin levels in patients with polymyositis. Eur Rev Med Pharmacol Sci 2016; 20: 631-5.
8. Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 1981; 78: 6858-62.

9. Yang D, Su Z, Wu S, et al. Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis. Int J Neurosci 2016; 126: 1120-6.
10. Su Q, Li X, Mo W, et al. Low serum bilirubin, albumin, and uric acid levels in patients with Crohn's disease. Medicine (Baltimore) 2019; 98: e15664.
11. Zhu F, Feng D, Zhang T, et al.Altered uric acid metabolism in isolated colonic Crohn's disease but not ulcerative colitis. J Gastroenterol Hepatol 2019; 34: 154-61.
12. Kekilli M, Tanoğlu A, Karaahmet F et al. Midkine level may be used as a noninvasive biomarker in Crohn's disease. Turk J Med Sci 2020; 50: 324-9.
13. Boehm D, Krzystek-Korpacka M, Neubauer K, et al. Lipid peroxidation markers in Crohn's disease: the associations and diagnostic value. Clin Chem Lab Med 2012; 50: 1359-66.
14. Wendland BE, Aghdassi E, Tam C, et al. Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease. Am J Clin Nutr 2001; 74: 259-64.
15. Koutroubakis IE, Malliaraki N, Dimoulios PD, et al. Decreased total and corrected antioxidant capacity in patients with inflammatory bowel disease. Dig Dis Sci 2004; 49: 1433-7.
16. Szczeklik K, Krzyściak W, Cibor DA, et al. Evaluation of plasma concentrations of selected antioxidant parameters in patients with active Crohn's disease. Folia Medica Cracoviensia 2018; 58: 119-30
17. Leníček M, Ďuricová D, Hradsky O, et al. The Relationship Between Serum Bilirubin and Crohn’s Disease. Inflamm Bowel Dis 2014; 20: 481-7.
18. Schieffer KM, Bruffy SM, Rauscher R, et al. Reduced total serum bilirubin levels are associated with ulcerative colitis. PloS one 2017; 12: e0179267.
19. Peng F, Yang Y, Liu J, et al. Low antioxidant status of serum uric acid, bilirubin and albumin in patients with neuromyelitis optica. Eur J Neurol 2012; 19: 277-83.
20. Li WC, Mo LJ, Shi X, et al. Antioxidant status of serum bilirubin, uric acid and albumin in pemphigus vulgaris. Clin Exp Dermatol 2018; 43: 158-63.
21. Neubauer K, Kempinski R, Matusiewicz M, et al. Nonenzymatic Serum Antioxidant Capacity in IBD and Its Association with the Severity of Bowel Inflammation and Corticosteroids Treatment. Medicina (Kaunas) 2019; 55: 88.
22. Lemarechal H, Allanore Y, Chenevier-Gobeaux C, et al. Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy. Clinica Chimica Acta 2006; 372: 147-53.
23. Pereira C, Grácio D, Teixeira JP, et al. Oxidative stress and DNA damage: implications in inflammatory bowel disease. Inflamm Bowel Dis 2015; 21: 2403-17.
24. Bednarek J, Wysocki H, Sowiński J. Peripheral parameters of oxidative stress in patients with infiltrative Graves' ophthalmopathy treated with corticosteroids. Immunol Lett 2004; 93: 227-32.