The use of Cytokeratin-18 and Interleukin-6 as Diagnostic Markers for Nonalcoholic Fatty Liver Disease in Iraqi young adult
Keywords:
Interleukin-6, Keratin-18, Non-alcoholic Fatty Liver DiseaseAbstract
Objective: to study the prevalence of nonalcoholic fatty liver disease in the studied group in Karbala, iraq and disease evaluation by inflammatory markers.
Method: a total of 816 patients referred for ultrasound checking, their aged (18-40) years they were studied to detect the prevalence of NAFLD. For comparison of level of CK18, IL-6 and other studied markers, we choose 45 patients with NAFLD, From the remaining standard individuals, we randomly selected 45 individuals as control group. Blood sample was collected to measured lipid profile, liver enzyme and CK-18, Enzyme-linked immune sorbent assay (ELISA) used for detecting and quantifying inflammatory markers.
Results: The result shows that serum CK-18 was highly significant in patient with non-alcoholic fatty liver disease when comparison with control groups (P = 0.001), also showed serum IL-6 no significant increase in patient with NALD than in control group (P <0.05).
Conclusion: The prevelance of NAFLD in the studied group (816 persons, age range 18-40 years) in Karbala, Iraq was 5,51%, and our result rely on finding from assays of inflammatory markers (cytokeratin 18 and IL6) and that most patient in this study were found to have steatohepatitis.
References
1. Italian Association for the Study of the Liver (AISF. AISF position paper on nonalcoholic fatty liver disease (NAFLD): updates and future directions. Digestive and Liver Disease. 2017 May 31;49(5):471-83.
2. Mohsen M. Maher , Wesam A. Ibrahim , Shereen A. Saleh , Lobna Shash , Hoda Abou Gabal , Mohammed Tarif , Mohammed Gamal.. Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. Egyptian Journal of Medical Human Genetics, 2015; 16(1), pp.41-46.
3. Sanal MG . Biomarkers in nonalcoholic fatty liver disease the empero has no clothes? , World J Gastroenterol .2015;21(11),pp. 3223-3231 .
4. Xinhuan Wei, MM,a Hongshan Wei, MD,b Wei Lin, MM,a Zhongjie Hu, MD,a and Jing Zhang, MDa. Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B . Medicine (Baltimore)2017;96(20),pp. e6807.
5. Gian Paolo Caviglia1, Rinaldo Pellicano. Serum Cytokeratin-18 Levels for Liver Fibrosis Prediction , Hepat Mon.2015; 15(8),pp. e30853.
6. Huang, J.F., Yeh, M.L., Huang, C.F., Huang, C.I., Tsai, P.C., Tai, C.M., Yang, H.L., Dai, C.Y., Hsieh, M.H., Chen, S.C. and Yu, M.L. Cytokeratin-18 and uric acid predicts disease severity in Taiwanese nonalcoholic steatohepatitis patients. PloS one.2017; 12(5), p.e0174394..
7. John Vizuete, Alfredo Camero, Mazyar Malakouti, Karthik Garapati1 and Julio Gutierrez,. Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and Future Therapies. Journal of Clinical and Translational Hepatology ,2017;5(1),pp.67-75 .
8. Su H, Lei CT and Zhang C. Interleukin-6 signaling pathway and its role in kidney disease: an update. Frontiers in Immunology.2017;8,pp.405 .
9. Vincent Braunersreuther, Giorgio Luciano Viviani, François Mach, and Fabrizio Montecucco. Role of cytokines and chemokines in non-alcoholic fatty liver disease . World J Gastroenterol,2012;18(8),pp. 727–735.
10. Haafsa Arshad Sahibzada , Zohaib Khurshid , Rabia Sannam Khan, Mustafa Naseem, Khalid Mahmood Siddique, Maria Mali and Muhammad Sohail Zafar , Salivary IL-8, IL-6 and TNF-_ as Potential Diagnostic Biomarkers for Oral Cancer . Diagnostics 2017, 7, 21.
11. Subir Kumar Das and V. Balakrishnan. Role of Cytokines in the Pathogenesis of Non-Alcoholic Fatty Liver Disease . Indian J Clin Biochem.2011; 26(2),pp. 202–209.
12. Rolla, S., Alchera, E., Imarisio, C., Bardina, V., Valente, G., Cappello, P., Mombello, C., Follenzi, A., Novelli, F. and Carini, R. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice. Clinical Science.2017;130(3), pp.193-203.
13. Paredes-Turrubiarte, G., González-Chávez, A., Pérez-Tamayo, R., Salazar-Vázquez, B.Y., Hernández, V.S., Garibay-Nieto, N., Fragoso, J.M. and Escobedo, G. Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients. Clinical and experimental medicine,2016; 16(2), pp.193-202.
14. Feliciano Chanana Paquissi. Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets. Frontiers in immunology.2016; 7,pp.490.
15. 15-Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M. Global epidemiology of nonalcoholic fatty liver disease—Metaâ€analytic assessment of prevalence, incidence, and outcomes. Hepatology.2016; 64(1), pp.73-84.
16. Michael H. Le, Pardha Devaki, Nghiem B. Ha, , Dae Won Jun5, Helen S. Te, Ramsey C. Cheung, Mindie H. Nguyen. Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States. PloS one,2017; 12(3), p.e0173499.
17. Elizabeth M. Brun, Vincent W. S. Wong, Valerio Nobili, Christopher P. Day, Silvia Sookoian, Jacquelyn J. Maher, Elisabetta Bugianesi, Claude B. Sirlin, Brent A. Neuschwander-Tetri and Mary E. Rinella, Nonalcoholic fatty liver disease. Article number: 15080 17 December 2015 voume 1.
18. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Digestive and Liver Disease.2015; 47(3), pp.181-190.
19. Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis.2015; 239(1), pp.192-202.
20. Pappachan, J.M., Antonio, F.A., Edavalath, M. and Mukherjee, A. Non-alcoholic fatty liver disease: a diabetologist’s perspective. Endocrine.2014;45(3), pp.344-353.
21. Hashimoto, E., Taniai, M. and Tokushige, K . Characteristics and diagnosis of NAFLD/NASH. Journal of gastroenterology and hepatology.2013; 28(S4), pp.64-70.
22. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103: 1372-1379 .
23. Naim Alkhouri; Ariel E. Feldstein. Noninvasive diagnosis of nonalcoholic fatty liver disease: are we there yet?. Metabolism.2016;65(8), pp.1087-1095.
24. Abiru, S., Migita, K., Maeda, Y., Daikoku, M., Ito, M., Ohata, K., Nagaoka, S., Matsumoto, T., Takii, Y., Kusumoto, K. and Nakamura, M. Serum cytokine and soluble cytokine receptor levels in patients with nonâ€alcoholic steatohepatitis. Liver International, 2006; 26(1), pp.39-45.
25. Bocsan, I.C., Milaciu, M.V., Pop, R.M., Vesa, S.C., Ciumarnean, L., Matei, D.M. and Buzoianu, A.D. Cytokines genotype-phenotype correlation in nonalcoholic steatohepatitis. Oxidative medicine and cellular longevity. 2017; 2017.
26. European Association for the Study of the Liver, European Association for theStudy of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fattyliver disease. Journal of Hepatology 2016; 64:1388–402.
27. Feldstein, A.E., Alkhouri, N., De Vito, R., Alisi, A., Lopez, R. and Nobili, V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. The American journal of gastroenterology.2013; 108(9), pp.1526-1531.
28. Liang, J., Liu, F., Wang, F., Han, T., Jing, L., Ma, Z. and Gao, Y. A Noninvasive Score Model for Prediction of NASH in Patients with Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease. BioMed research international. 2017; 2017.
29. Fadhil Jawad Al-tuma, Hedef Dafer El-yassin and Kammela Hadi Shammam,. Alcohol dehydrogenase genotype (ADH2 and ADH3) in alcoholism of Iraqi people, J Cont Med Sci 2015, vol 1. No 2, pp:9-13.
30. Cusi, K., Chang, Z., Harrison, S., Lomonaco, R., Bril, F., Orsak, B., Ortiz-Lopez, C., Hecht, J., Feldstein, A.E., Webb, A. and Louden, C. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. Journal of hepatology, 2014; 60(1), pp.167-174.
2. Mohsen M. Maher , Wesam A. Ibrahim , Shereen A. Saleh , Lobna Shash , Hoda Abou Gabal , Mohammed Tarif , Mohammed Gamal.. Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. Egyptian Journal of Medical Human Genetics, 2015; 16(1), pp.41-46.
3. Sanal MG . Biomarkers in nonalcoholic fatty liver disease the empero has no clothes? , World J Gastroenterol .2015;21(11),pp. 3223-3231 .
4. Xinhuan Wei, MM,a Hongshan Wei, MD,b Wei Lin, MM,a Zhongjie Hu, MD,a and Jing Zhang, MDa. Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B . Medicine (Baltimore)2017;96(20),pp. e6807.
5. Gian Paolo Caviglia1, Rinaldo Pellicano. Serum Cytokeratin-18 Levels for Liver Fibrosis Prediction , Hepat Mon.2015; 15(8),pp. e30853.
6. Huang, J.F., Yeh, M.L., Huang, C.F., Huang, C.I., Tsai, P.C., Tai, C.M., Yang, H.L., Dai, C.Y., Hsieh, M.H., Chen, S.C. and Yu, M.L. Cytokeratin-18 and uric acid predicts disease severity in Taiwanese nonalcoholic steatohepatitis patients. PloS one.2017; 12(5), p.e0174394..
7. John Vizuete, Alfredo Camero, Mazyar Malakouti, Karthik Garapati1 and Julio Gutierrez,. Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and Future Therapies. Journal of Clinical and Translational Hepatology ,2017;5(1),pp.67-75 .
8. Su H, Lei CT and Zhang C. Interleukin-6 signaling pathway and its role in kidney disease: an update. Frontiers in Immunology.2017;8,pp.405 .
9. Vincent Braunersreuther, Giorgio Luciano Viviani, François Mach, and Fabrizio Montecucco. Role of cytokines and chemokines in non-alcoholic fatty liver disease . World J Gastroenterol,2012;18(8),pp. 727–735.
10. Haafsa Arshad Sahibzada , Zohaib Khurshid , Rabia Sannam Khan, Mustafa Naseem, Khalid Mahmood Siddique, Maria Mali and Muhammad Sohail Zafar , Salivary IL-8, IL-6 and TNF-_ as Potential Diagnostic Biomarkers for Oral Cancer . Diagnostics 2017, 7, 21.
11. Subir Kumar Das and V. Balakrishnan. Role of Cytokines in the Pathogenesis of Non-Alcoholic Fatty Liver Disease . Indian J Clin Biochem.2011; 26(2),pp. 202–209.
12. Rolla, S., Alchera, E., Imarisio, C., Bardina, V., Valente, G., Cappello, P., Mombello, C., Follenzi, A., Novelli, F. and Carini, R. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice. Clinical Science.2017;130(3), pp.193-203.
13. Paredes-Turrubiarte, G., González-Chávez, A., Pérez-Tamayo, R., Salazar-Vázquez, B.Y., Hernández, V.S., Garibay-Nieto, N., Fragoso, J.M. and Escobedo, G. Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients. Clinical and experimental medicine,2016; 16(2), pp.193-202.
14. Feliciano Chanana Paquissi. Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets. Frontiers in immunology.2016; 7,pp.490.
15. 15-Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M. Global epidemiology of nonalcoholic fatty liver disease—Metaâ€analytic assessment of prevalence, incidence, and outcomes. Hepatology.2016; 64(1), pp.73-84.
16. Michael H. Le, Pardha Devaki, Nghiem B. Ha, , Dae Won Jun5, Helen S. Te, Ramsey C. Cheung, Mindie H. Nguyen. Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States. PloS one,2017; 12(3), p.e0173499.
17. Elizabeth M. Brun, Vincent W. S. Wong, Valerio Nobili, Christopher P. Day, Silvia Sookoian, Jacquelyn J. Maher, Elisabetta Bugianesi, Claude B. Sirlin, Brent A. Neuschwander-Tetri and Mary E. Rinella, Nonalcoholic fatty liver disease. Article number: 15080 17 December 2015 voume 1.
18. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Digestive and Liver Disease.2015; 47(3), pp.181-190.
19. Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis.2015; 239(1), pp.192-202.
20. Pappachan, J.M., Antonio, F.A., Edavalath, M. and Mukherjee, A. Non-alcoholic fatty liver disease: a diabetologist’s perspective. Endocrine.2014;45(3), pp.344-353.
21. Hashimoto, E., Taniai, M. and Tokushige, K . Characteristics and diagnosis of NAFLD/NASH. Journal of gastroenterology and hepatology.2013; 28(S4), pp.64-70.
22. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103: 1372-1379 .
23. Naim Alkhouri; Ariel E. Feldstein. Noninvasive diagnosis of nonalcoholic fatty liver disease: are we there yet?. Metabolism.2016;65(8), pp.1087-1095.
24. Abiru, S., Migita, K., Maeda, Y., Daikoku, M., Ito, M., Ohata, K., Nagaoka, S., Matsumoto, T., Takii, Y., Kusumoto, K. and Nakamura, M. Serum cytokine and soluble cytokine receptor levels in patients with nonâ€alcoholic steatohepatitis. Liver International, 2006; 26(1), pp.39-45.
25. Bocsan, I.C., Milaciu, M.V., Pop, R.M., Vesa, S.C., Ciumarnean, L., Matei, D.M. and Buzoianu, A.D. Cytokines genotype-phenotype correlation in nonalcoholic steatohepatitis. Oxidative medicine and cellular longevity. 2017; 2017.
26. European Association for the Study of the Liver, European Association for theStudy of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fattyliver disease. Journal of Hepatology 2016; 64:1388–402.
27. Feldstein, A.E., Alkhouri, N., De Vito, R., Alisi, A., Lopez, R. and Nobili, V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. The American journal of gastroenterology.2013; 108(9), pp.1526-1531.
28. Liang, J., Liu, F., Wang, F., Han, T., Jing, L., Ma, Z. and Gao, Y. A Noninvasive Score Model for Prediction of NASH in Patients with Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease. BioMed research international. 2017; 2017.
29. Fadhil Jawad Al-tuma, Hedef Dafer El-yassin and Kammela Hadi Shammam,. Alcohol dehydrogenase genotype (ADH2 and ADH3) in alcoholism of Iraqi people, J Cont Med Sci 2015, vol 1. No 2, pp:9-13.
30. Cusi, K., Chang, Z., Harrison, S., Lomonaco, R., Bril, F., Orsak, B., Ortiz-Lopez, C., Hecht, J., Feldstein, A.E., Webb, A. and Louden, C. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. Journal of hepatology, 2014; 60(1), pp.167-174.
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Published
2019-09-26
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Qassam SA, Nada SZ, Ahmed ZK. The use of Cytokeratin-18 and Interleukin-6 as Diagnostic Markers for Nonalcoholic Fatty Liver Disease in Iraqi young adult. Iraq Med J [Internet]. 2019 Sep. 26 [cited 2024 Nov. 4];3(3). Available from: https://iraqmedj.org/index.php/imj/article/view/688
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