sdü tıp fak derg Medical Journal of Süleyman Demirel University 2602-2109 Süleyman Demirel Üniversitesi 10.17343/sdutfd.738119 Clinical Sciences Klinik Tıp Bilimleri Otoimmün karaciğer hastalığında oksidatif dengesizlik: oksidan-antioksidan durumun ve iskemi modifiye albüminin değerlendirilmesi Oxidative imbalance in autoimmune liver disease: evaluation of oxidant-antioxidant status and ischemia-modified albumin https://orcid.org/0000-0002-7057-171X Karakoyun Inanc University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry https://orcid.org/0000-0002-2104-6783 Ulaşoğlu Celal Istanbul Medeniyet University, Goztepe Training and Research Hospital, Department of Gastroenterology https://orcid.org/0000-0003-0766-0303 Arslan Fatma Demet University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry https://orcid.org/0000-0002-4845-9203 Onur Selin University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry https://orcid.org/0000-0003-1071-1263 İyilikci Veli University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry https://orcid.org/0000-0002-1483-997X Basok Banu Isbilen University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry https://orcid.org/0000-0003-4910-0128 Çolak Ayfer University of Health Sciences, Tepecik Training and Research Hospital, Department of Medical Biochemistry 03 11 2021 28 1 127 135 05 20 2020 09 09 2020 Copyright © 1994, Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1994 Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

Amaç: Bu çalışmada, otoimmün karaciğer hastalığında (AILD) belirteç olarak total antioksidan durum (TAS), oksidatif stres indeksi (OSI), total oksidan durum (TOS), iskemi modifiye albumin (IMA) ve iskemi modifiye albumin oranının (IMAR) yararı değerlendirildi.Gereç ve Yöntem: Çalışma, 22'si otoimmün hepatit (AIH), 32'si primer biliyer kolanjit (PBC) ve 12'si AIH/PBC örtüşme sendromu olan toplam 66 AILD hastası ve 49 sağlıklı kontrol içermekteydi. Serum TAS, TOS, IMA, albumin (Alb), laktat dehidrojenaz (LDH), alkalen fosfataz (ALP), aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), total bilirubin (TBil), direkt bilirubin (DBil) ve 25-hidroksivitamin D (25 [OH] D) analiz edildi. OSI, TOS/TAS olarak hesaplandı ve IMAR, IMA ve Alb'den türetildi.Bulgular: Serum TAS, TOS, OSI, IMA ve IMAR değerleri AILD grubunda kontrollere göre anlamlı olarak daha yüksekti (sırasıyla p=0.004,

Objective: Current study evaluated the utility of total antioxidant status (TAS), oxidative stress index (OSI), total oxidant status (TOS), ischemia-modified albumin (IMA), and ischemia-modified albumin ratio (IMAR) as markers in autoimmune liver disease (AILD).Material and Methods: The study included a total of 66 AILD patients, 22 with autoimmune hepatitis (AIH), 32 with primary biliary cholangitis (PBC), and 12 with AIH/PBC overlap syndrome, and 49 healthy controls. Serum TAS, TOS, IMA, albumin (Alb), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), and 25-hydroxyvitamin D (25[OH]D) were analyzed. OSI was calculated as TOS/TAS and IMAR was derived from IMA and Alb.Results: Serum TAS, OSI, TOS, IMA, and IMAR values were found to be significantly higher in the AILD group compared to controls (p=0.004,

 Autoimmune liver disease ischemia-modified albumin total antioxidant status total oxidant status Otoimmün karaciğer hastalığı iskemi modifiye albumin total antioksidan durum total oksidan durum Destekleyen kurum bulunmamaktadır. 1. Floreani A, De Martin S, Secchi MF, Cazzagon N. Extrahepatic autoimmunity in autoimmune liver disease. European Journal of Internal Medicine 2019;59:1-7. 2. Hong-Ying Pan, Yi-Ning Dai, Ji-Na Zheng, Ke-Qing Shi, Sven Van Poucke, et al. National incidence of autoimmune liver diseases and its relationship with the human development index. Oncotarget 2016;7(29):46273–282. 3. Nayagam JS, Miquel R, Joshi D. Overlap Syndrome with Autoimmune Hepatitis and Primary Sclerosing Cholangitis. European Medical Journal Hepatology 2019;7(1):95-104. 4. Liberal R, Grant CR. Cirrhosis and autoimmune liver disease: Current understanding. World Journal of Gastroenterology 2016;8(28):1157-68. 5. Czaja AJ. Autoimmune liver disease. Current Opinion in Gastroenterology 2009;25:215-22. 6. Penz-Österreicher M, Österreicher CH, Trauner M. Fibrosis in autoimmune and cholestatic liver disease. Best Practice & Research Clinical Gastroenterology 2011;25(2):245-58. 7. Moreira RK, Revetta F, Koehler E, Washington MK. Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease. World Journal of Gastroenterology 2010; 16(4):453-7. 8. Bogdanos DP, Invernizzi P, Mackay IR, Vergani D. Autoimmune liver serology: current diagnostic and clinical challenges. World Journal of Gastroenterology 2008;14:3374-87. 9. Czaja AJ. Autoantibodies as prognostic markers in autoimmune liver disease. Digestive Diseases and Sciences 2010;55(8):2144-61. 10. Zen Y, Notsumata K, Tanaka N, Nakanuma Y. Hepatic centrilobular zonal necrosis with positive antinuclear antibody: a unique subtype or early disease of autoimmune hepatitis? Human Pathology 2007;38:1669–75. 11. Miyake Y, Iwasaki Y, Terada R, et al. Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis. Hepatology Research 2007;37:801–5. 12. Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, et al. Review article: autoimmune hepatitis – its aetiopathogenesis, clinical features, diagnosis and management. Alimentary Pharmacology & Therapeutics 2013;38:887–913. 13. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, et al; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology 2009;50:291–308. 14. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, et al. American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010;51:660–78. 15. Ramachandran A, Jaeschke H. Oxidative Stress and Acute Hepatic Injury. Current Opinion in Toxicology 2018;7:17-21. 16. Ljubuncic P, Tann Z, Bomzon A. Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease. Gut 2000;47:710–6. 17. Medina J, Moreno-Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 2005;65(17):2445-61. 18. Pemberton PW, Aboutwerat A, Smith A, Burrows PC, McMahon RF, et al. Oxidant stress in type I autoimmune hepatitis: the link between necroinflammation and fibrogenesis? Biochimica et Biophysica Acta 2004;1689:182–9. 19. Beyazit Y, Efe C, Tanoglu A, Purnak T, Sayilir A, et al. Nitric oxide is a potential mediator of hepatic inflammation and fibrogenesis in autoimmune hepatitis. Scandinavian Journal of Gastroenterology 2015;50(2):204-10. 20. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry 2004;37:277–85. 21. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry 2005;38:1103–11. 22. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. The Journal of Emergency Medicine 2000;19:311–5. 23. Lippi G, Montagnana M, Salvagno GL, Guidi GC. Standardization of ischemia-modified albumin testing: adjustment for serum albumin. Clinical Chemistry and Laboratory Medicine 2007;45(2):261-2. 24. Hosmer DW and Lemeshow S. Assessing the Fit of the Model in Applied Logistic Regression NY, John Wiley & sons 2000, 160-164. 25. Aboutwerat A, Pemberton PW, Smith A, Burrows PC, McMahon RF, et al. Oxidant stress is a significant feature of primary biliary cirrhosis. Biochimica et Biophysica Acta 2003;1637: 142–50. 26. Sanz-Cameno P, Medina J, García-Buey L, García-Sánchez A, Borque MJ, et al. Enhanced intrahepatic inducible nitric oxide synthase expression and nitrotyrosine accumulation in primary biliary cirrhosis and autoimmune hepatitis. Journal of Hepatology 2002;37:723–9. 27. Sirmatel O, Sert C, Sirmatel F, Selek S, Yokus B. Total antioxidant capacity, total oxidant status and oxidative stress index in the men exposed to 1.5 T static magnetic field. General Physiology and Biophysics 2007;26(2):86-90. 28. Baser H, Can U, Baser S, Hidayetoglu BT, Aslan U, et al. Serum total oxidant/anti-oxidant status, ischemia-modified albumin and oxidized-low density lipoprotein levels in patients with vitamin D deficiency. Archives of Endocrinology and Metabolism 2015;59(4):318-24. 29. Czaja AJ. Nature and Implications of Oxidative and Nitrosative Stresses in Autoimmune Hepatitis. Digestive Diseases and Sciences 2016;61(10):2784-803. 30. Selek S, Cosar N, Kocyigit A, Erel O, Aksoy N, et al. PON1 activity and total oxidant status in patients with active pulmonary tuberculosis. Clinical Biochemistry 2008;41(3):140-4. 31. Aydemir C, Dilli D, Uras N, Ulu HO, Oguz SS, et al. Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis. Journal of Pediatric Surgery 2011; 46(11):2096-100. 32. H Karsen, I Binici, M Sunnetcioglu, AI Baran, MR Ceylan, et al. Association of paraoxonase activity and atherosclerosis in patients with chronic hepatitis B. African Health Sciences 2012;12(2):114–8. 33. Pirgon Ö, Bilgin H, Çekmez F, Kurku H, Dündar BN. Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease. Journal of Clinical Research in Pediatric Endocrinology 2013;5(1):33-9. 34. Demiroren K, Dogan Y, Kocamaz H, Ozercan IH, Ilhan S, et al. Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis. Clinics and Research in Hepatology and Gastroenterology 2014;38(1):63-72. 35. Bilgili S, Bozkaya G, Tütüncüler FK, Akşit M, Yavuz M. Investigation of ischemia modified albumin levels in iron deficiency anemia. Turkish Journal of Biochemistry 2017; 42(3):259-64. 36. Kaefer M, Piva SJ, De Carvalho JA, Da Silva DB, Becker AM, et al. Association between ischemia modified albumin, inflammation and hyperglycemia in type 2 diabetes mellitus. Clinical Biochemistry 2010;43:450–4. 37. Sinha MK, Roy D, Gaze DC, Collinson PO, Kaski JC. Role of ‘‘ischemia modified albumin’’, a new biochemical marker of myocardial ischemia, in the early diagnosis of acute coronary syndromes. Emergency Medicine Journal 2004;21:29–34. 38. Duarte MM, Rocha JB, Moresco RN, Duarte T, Da Cruz IB, et al. Association between ischemia-modified albumin, lipids and inflammation biomarkers in patients with hypercholesterolemia. Clinical Biochemistry 2009;42:666–71. 39. Cichota LC, Moresco RN, Duarte MM, da Silva JE. Evaluation of ischemia-modified albumin in anemia associated to chronic kidney disease. Journal of Clinical Laboratory Analysis 2008;22:1–5. 40. Cakir M, Karahan SC, Mentese A, Sag E, Cobanoglu U, et al. Ischemia-Modified Albumin Levels in Children with Chronic Liver Disease. Gut Liver 2012;6(1):92–7. 41. Kumar PA, Subramanian K. The Role of Ischemia Modified Albumin as a Biomarker in Patients with Chronic Liver Disease. Journal of Clinical and Diagnostic Research 2016; 10(3):BC09–BC12. 42. Horoz M, Bolukbas C, Bolukbas FF, Sabuncu T, Aslan M, et al. Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis. BMC Gastroenterology 2005;5:35. 43. Şen V, Uluca Ü, Ece A, Kaplan İ, Bozkurt F, et al. Serum prolidase activity and oxidant–antioxidant status in children with chronic hepatitis B virus infection. Italian Journal of Pediatrics 2014;40:95. 44. Selek S, Herken H, Bulut M, Ceylan MF, Celik H, et al. Oxidative imbalance in obsessive compulsive disorder patients: a total evaluation of oxidant-antioxidant status. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2008;32(2):487-91. 45. Verit FF, Erel O, Kocyigit A. Association of increased total antioxidant capacity and anovulation in nonobese infertile patients with clomiphene citrate-resistant polycystic ovary syndrome. Fertility and Sterility 2007;88(2):418-24. 46. Smyk DS, Orfanidou T, Invernizzi P, Bogdanos DP, Lenzi M. Vitamin D in autoimmune liver disease. Clinics and Research in Hepatology and Gastroenterology 2013;37(5):535-45. 47. Efe C, Kav T, Aydin C, Cengiz M, Imga NN, et al. Low serum vitamin D levels are associated with severe histological features and poor response to therapy in patients with autoimmune hepatitis. Digestive Diseases and Sciences 2014;59(12):3035-42. 48. Sharifi N, Amani R, Hajiani E, Cheraghian B. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial. Endocrine 2014;47(1):70-80.