Çocukluk Çağı Metabolik Disfonksiyonla İlişkili Steatotik Karaciğer Hastalığında Hematolojik Biyobelirteçlerin Değerlendirilmesi

Öz

Amaç: Çalışmamızda Metabolik Disfonksiyonla İlişkili Steatotik Karaciğer Hastalığı (MASLD) tanılı çocuklarda inflamasyon temelli biyobelirteçlerin klinik önemi ve tanısal değerini araştırmayı amaçladık. Yöntemler: Bu Çalışma, Temmuz 2022-Ocak 2023 tarihleri arasında xxÜniversitesi Çocuk Gastroenteroloji bölümünde takip edilen hasta dosyalarının retrospektif olarak değerlendirilmesi ile gerçekleştirilmiştir.AASLD ve EASL kriterlerine göre tanı konulan 120 MASL hastası ve 80 sağlıklı kontrol grubu ile çalışma tamamlanmıştır.Laboratuvar değerleri ve bunlar aracılığı ile formüller hesaplanarak karşılaştırmalar yapılmıştır. Bulgular: Hasta grubunda 50(%41.7) kız, 70(%58.3) erkek ve kontrol grubunda ise 40 kız (%50.0), 40 erkek(%50.0) idi.Karaciğer Ultrasonografilerinde Grade 0 tespit edilen 80 hasta kontrol grubu;102’si(%85)Grade 1 ve 18’i(%15)Grade 2-3 hasta grubu olarak kabul edildi. Hastaların değerleri, sağlıklı gönüllülerin değerleri ile karşılaştırıldı.Yapılan testlerde hastalarda WBC, nötrofil, lenfosit, platelet, MHO, RPO, RLO, MPO, WMO, GPO, Sİİ ve FIB-4 skor değerleri karaciğer Gradelendirilmesine göre karşılaştırıldığında korelasyon tespit edildi. Sonuç: MASLD’ın erken tespiti için etkili bir izleme göstergesine acilen ihtiyaç duyulmaktadır.Yapmış olduğumuz bu çalışma, kişilerde MASL varlığının araştırılması gerektiğini, erken tanı ve tedavi yaklaşımları ile olası komplikasyonların önüne geçilebileceğini düşündürmektedir.Sonuç olarak MASLD’den şüphelenilen, ileri tetkik ve tedaviye ihtiyaç duyan hastaların basit ve hızlı bir şekilde tespiti için hematolojik biyobelirteçlerin kullanımı faydalı olacağı düşüncesindeyiz.

Anahtar Kelimeler

• metabolik disfonksiyonla ilişkili steatotik karaciğer hastalığı
• çocukluk çağı
• biobelirteç
• yağlı karaciğer hastalığı

Evaluation of Hematological Biomarkers in Childhood Metabolic Dysfunction Associated Steatotic Liver Disease

Öz

Aim:We aimed to investigate the clinical significance and diagnostic value of inflammation-based biomarkers in children with a diagnosis of Metabolic Dysfunction Associated Steatotic Liver Disease(MASLD). Methods:This study was carried out by retrospectively evaluating the files of patients followed up in the Department of Pediatric Hepatology at xxUniversity between July 2022 and January 2023.The study was completed with 120 patients with MASLD diagnosed according to the criteria of the AASLD and EASL, 80 healthy controls.Comparisons were made by calculating laboratory values and formulas through them. Results:There were 50(41.7%)girls and 70(58.3%)boys in the patient group,and 40 girls (50.0%) and 40 boys(50.0%) in the control group.While 80 patients with Grade 0 detected in liver ultrasonography were taken as the control group;102(85%) Grade 1 and 18(15%)Grade 2-3 patients were considered as the patient group.The values of the patients were compared with the values of healthy volunteers.When the WBC, neutrophil, lymphocyte, platelet, MHR, RPR, RLR, MPR, WMR, GPR, SII and FIB-4score values were compared according to liver grading, a correlation was found in the tests performed on the patients. Conclusion:Our study suggests that the presence of MASLD should be investigated in individuals, and possible complications can be prevented with early diagnosis and treatment approaches.As a result, we think that the use of hematological biomarkers will be useful for the simple and rapid detection of patients with suspected MASLD and who need further examination and treatment.

Anahtar Kelimeler

• Metabolic Dysfunction Associated Steatotic Liver Disease
• Chıldhood
• biomarker
• fatty liver disease

Kaynakça

1. 1-Ludwig, J., et al., Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc, 1980. 55(7): 434-8.
2. 2-Eslam, M., et al., MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology, 2020. 158(7): 1999-2014 e1.
3. 3- Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol. 2023 20:101133. doi: 10.1016/j.aohep.2023.101133.
4. 4-Shah J, Okubote T, Alkhouri N. Overview of Updated Practice Guidelines for Pediatric Nonalcoholic Fatty Liver Disease. Gastroenterol Hepatol (N Y) 2018; 14: 407–14.
5. 5-Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67: 328–57.
6. 6-Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS One 2015; 10: e0140908.
7. 7-Shaunak M, Byrne CD, Davis N, Afolabi P, Faust SN, Davies JH. Nonalcoholic fatty liver disease and childhood obesity. Arch Dis Child. 2021;106:3– 8.
8. 8-Gokce S, Atbinici Z, Aycan Z, Çınar HG, Zorlu P. The relationship between pediatric non-alchololic fatty liver disease and cardiovasculer risk factors and increased risk of atherosclerosşs in obese children. Pediatr Cardiol 2013; 34: 308–15.

9. 9-Akcam M, Boyaci A, Pirgon O, Koroglu M, Dundar BN. Importance of the liver ultrasound scores in pubertal obese children with nonalcoholic fatty liver disease. Clin Imaging 2013; 37: 504–8
10. 10- Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212–24.
11. 11- Türkiye Karaciğer Araştırmaları Derneği. Alkol dışı yağlı karaciğer hastalığı (NAFLD) klinik rehberi. Ankara; 2021. s. 11-51.
12. 12-Söderberg C, Stål P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595–602.
13. 13- Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 2018; 24:908–922.
14. 14-Schuster S, Cabrera D, Arrese M, Feldstein AE. Triggering and resolution of inflammation in NASH. Nat Rev Gastroenterol Hepatol 2018; 15(6):349–64.
15. 15-Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol 2016; 26(3):372–6.
16. 16- Lee J, Vali Y, Boursier | Jerome, Spijker R, Anstee QM, Patrick |, et al. Prognostic accuracy of FIB-4, NAFLD fibrosis score and APRI for NAFLD-related events: A systematic review. Liver International. 2021;41:261–70.
17. 17- Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ, et al. Comparison of Noninvasive Markers of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Clinical Gastroenterology and Hepatology. 2009;7(10):1104–12.
18. 18- Yajima Y, Ohta K, Narui T, Abe R, Suzuki H, Ohtsuki M. Ultrasonografical diagnosis of fatyy liver: Significance of the liver-kidney contrast. Tohoku J Exp Med 1983;139:43-50.
19. 19- Rumack CM. Diagnostic Ultrasound. In: Rumack CM, Editor. St Louis: Mosby;1998.pp.
20. 20- Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G: Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007, 30(5):1212-8.
21. 21- Alkhouri N, Tamimi TA, Yerian L, Lopez R, Zein NN, Feldstein AE: The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Dig Dis Sci 2010, 55(9):2644-50.
22. 22- Mirbagheri SA, Rashidi A, Abdi S, Saedi D, Abouzari M: Liver: an alarm for the heart? Liver Int 2007, 27(7):891-4
23. 23- Y. U. Budak, M. Polat, and K. Huysal. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review. Biochemia Medica 2016; 26(2);178–193.
24. 24-Totani L, Evangelista V. Platelet-leukocyte interactions in cardiovascular disease and beyond. Arterioscler Thromb Vasc Biol 2010;30:2357-61.
25. 25-Kilciler G, Genc H, Tapan S, Ors F, et al. Mean platelet volume and its relationship with carotid atherosclerosis in subjects with non-alcoholic fatty liver disease. Ups J Med Sci. 2010;115(4):253-9.
26. 26- Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, et al. Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Dig Dis Sci. 2007;52(6):1535–9.
27. 27-Yoneda M, Fujii H, Sumida Y, Hyogo H, Itoh Y, Ono M, et al. Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46(11):1300–6.
28. 28-Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, UnalpArida A, Tonascia J, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology. 2010;52(3):913–24.
29. 29-Cao W, Zhao C, Shen C, Wang Y. Cytokeratin 18, alanine aminotransferase, platelets and triglycerides predict the presence of nonalcoholic steatohepatitis. PLoS One. 2013;8(12) e82092.
30. 30-Ciftci, A., B. Yilmaz, S. Koklu, O. Yuksel, M. Ozsoy, G. Erden, et al., Serum levels of nitrate, nitrite and advanced oxidation protein products (AOPP) in patients with nonalcoholic fatty liver disease. Acta Gastroenterol Belg 2015;78(2):201-5.
31. 31-Milovanovic Alempijevic, T., M. Stojkovic Lalosevic, I. Dumic, N. Jocic, A. Pavlovic Markovic, S. Dragasevic, et al., Diagnostic Accuracy of Platelet Count and Platelet Indices in Noninvasive Assessment of Fibrosis in Nonalcoholic Fatty Liver Disease Patients. Can J Gastroenterol Hepatol, 2017. 2017: p. 6070135.
32. 32- Celikbilek, M., S. Gursoy, K. Deniz, A. Karaman, G. Zararsiz, and A. Yurci, Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease. Platelets, 2013. 24(3): p. 194-9.
33. 33-Farkas N, Szabo A, Lorand V, et al. Clinical usefulness of measuring red blood cell distribution width in patients with systemic sclerosis. Rheumatol (Oxford) 2014;53:1439–45.
34. 34- Ferrucci L, Guralnik JM, Woodman RC, Bandinelli S, Lauretani F, Corsi AM, et al. Proinflammatory state and circulating erythropoietin in persons with and without anemia. Am J Med 2005; 118: 1288.
35. 35-Hampole CV, Mehrotra AK, Thenappan T, Gomberg-Maitland M, Shah SJ. Usefulness of red cell distribution width as a prognostic marker in pulmonary hypertension. Am J Cardiol 2009;104:868-72.
36. 36- Kim HM, Kim BS, Cho YK, et al. Elevated red cell distribution width is associated with advanced fibrosis in NAFLD. Clin Mol Hepatol 2013;19:258–65.
37. 37-Juarez-Hernandez E, Chávez-Tapia NC, Brizuela-Alcántara, DC, et. al. Association Between Serum Hemoglobin Levels and Non Alcoholic Fatty Liver Disease in a Mexican Population. Ann Hepatol, 2018. 17(4): p. 577-84.
38. 38-Chung, G.E., J.Y. Yim, D. Kim, M.S. Kwak, J.I. Yang, S.J. Chung, et al., Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease. Dig Liver Dis, 2017. 49(1):57-62.
39. 39-Wang S, Zhang G, Zhang Z, et al., Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: a prospective cohort study. BMJ Open, 2016. 6(6): p. e010342.
40. 40- Lee YJ, Lee HR, Shim JY, Moon BS, Lee JH, Kim JK. Relationship between white blood cell count and nonalcoholic fatty liver disease. Dig. Liver Dis. 2010, 42, 888–94.
41. 41- Yu YY, Cai JT, Song ZY, Tong YL, Wang JH. The associations among Helicobacter pylori infection, white blood cell count and nonalcoholic fatty liver disease in a large Chinese population. Medicine 2018, 97, e13271.
42. 42- Chung GE, Yim JY, Kim D, Kwak MS, Yang JI, Chung SJ, Yang SY, Kim JS. Associations between White Blood Cell Count and the Development of Incidental Nonalcoholic Fatty Liver Disease. Gastroenterol. Res. Pract. 2016, 2016, 7653689.
43. 43- Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury: present concepts. J Gastroenterol Hepatol 2011; 26(Suppl 1):173-9.
44. 44- Zhou Y, Tian N, Li P, He Y, Tong L, Xie W. The correlation between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with nonalcoholic fatty liver disease: a cross-sectional study. Eur J Gastroenterol Hepatol. 2022;34(11):1158-1164.
45. 45- Van Rooyen DM, Larter CZ, Haigh WG, Yeh MM, Ioannou G, Kuver R, et al. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology 2011; 141:1393–403.
46. 46-Gong P, Liu Y, Gong Y, Chen G, Zhang X, Wang S, et al. The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke. J Neuroinflammation. 2021;18:51.
47. 47-Vukicevic P, Klisic A, Neskovic V, Babic L, Mikic A, Bogavac-Stanojevic N, et al. New markers of platelet activation and reactivity and oxidative stress parameters in patients undergoing coronary artery bypass grafting. Oxid Med Cell Longev. 2021; 2021:8915253.
48. 48-Emre AR, Yasar KA, Atakan Y, Orhan C, Murathan K. Relationship between white blood count to mean platelet volume ratio and clinical outcomes and severity of coronary artery disease in patients undergoing primary percutaneous coronary intervention. Cardiovasc Ther. 2020; 2020:9625181.
49. 49-Guetl K, Raggam RB, Muster V, Gressenberger P, Vujic J, Avian A, Hafner F, Wehrschuetz M, Brodmann M, Gary T. The White blood cell count to mean platelet volume ratio for the prediction of chronic limb-threatening ischemia in lower extremity artery disease. J Clin Med. 2019;8(10):1593.
50. 50- Chen M, Wang B, Huang j, Zhao J, Chen J, Chen G. The role of platelet-related parameters for the prediction of NAFLD in OSAHS patients. BMC Pulm Med. 2022;22(1):487 51-Sun T, Shen H, Guo Q, et al. Association between Neutrophil Percentage-to-Albumin Ratio and All-Cause Mortality in Critically Ill Patients with Coronary Artery Disease. Biomed Res Int. 2020 ;2020:8137576.
51. 52- Ferro M, Babă DF, de Cobelli O, et al. Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy. Future Sci OA. 2021 ;7(7):FSO709.
52. 53-Liu CF, Chien LW. Predictive Role of Neutrophil-Percentage-to-Albumin Ratio (NPAR) in Nonalcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Nondiabetic US Adults: Evidence from NHANES 2017–2018. Nutrients 2023;5(8):1892.
53. 54- Zhou WJ, Yang J, Zhang G, Hu ZQ, Jiang YM, Yu F. Association between red cell distribution width-to-platelet ratio and hepatic fibrosis in nonalcoholic fatty liver disease: A cross-sectional study.Medicine, 2019;98(30).
54. 55-Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. Journal of Leukocyte Biology 2007;81(3):584-92.
55. 56- Akboga MK, Balci KG, Maden O, Ertem AG, Kirbas O, Yayla C, et al. Usefulness of monocyte to HDL-cholesterol ratio to predict high SYNTAX score in patients with stable coronary artery disease. Biomark Med. 2016;10(4):375–83.
56. 57-Zhang Y, Li S, Guo YL, et. al. Is monocyte to HDL ratio superior to monocyte count in predicting the cardiovascular outcomes: evidence from a large cohort of Chinese patients undergoing coronary angiography. Annals of Medicine 2016;48(5):305-12.
57. 58- Yozgat A, Ekmen N, Kasapoglu B, Unsal Y, Sokmen F, Kekilli M. Monocyte/HDL ratio in non-alcoholic hepatic steatosi. Arq Gastroenterol. (2021) 58:439–42.
58. 59- Huang H, Wang Q, Shi X, Chen Y, Shen C, Zhang J, Xu C. Association between monocyte to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a cross-sectional study. Mediat Inflamm. 2021:6642246.
59. 60-Wang L, Dong J, Xu M, Li L, Yang N, Qian G. Association between monocyte to high-density lipoprotein cholesterol ratio and risk of non-alcoholic fatty liver disease: a cross-sectional study. Front Med (Lausanne). 2022 ;9:898931. doi: 10.3389/fmed.2022.898931.
60. 61- Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al.Fibrosis stage is the strongest predictor for disease specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2014; 61(5), 1547-54.
61. 62- Lemoine M, Shimakawa Y, Nayagam S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016; 65:1369–76.
62. 63- Schiavon LL, Narciso-Schiavon JL, Ferraz ML, Silva AE, Carvalho-Filho RJ. The gamma-glutamyl transpeptidase to platelet ratio (GPR) in HBV patients: just adding up? Gut. 2016;66(6):1169-70.
63. 64-Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conje evaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38(2): 518-26.
64. 65-Kruger FC, Daniels CR, Kidd M, Swart G, Brundyn G, Kotze M. APRI:A simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH. S Afr Med J 2011:6;477-80.
65. 66- Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006; 43: 1317-25.
66. 67- Sumida Y, Yoneda M, Hyogo H, Itoh Y, Ono M, Fujii H, Eguchi Y,Fujii H, Suzuki Y, Aoki N, Kanemasa K. Validation of FIB-4 index in a Japanese fatty liver disease population BMC gastroenterology 2012;12;1-9.