CYTOKERATIN-18 AS A MARKER OF NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE ADOLESCENTS
Аннотация
In parallel with the obesity epidemic in the world, the prevalence of non-alcoholic fatty liver disease among children and adolescents is growing. Current data suggest that insulin resistance is one of the main factors in the pathogenesis of non-alcoholic fatty liver disease, and the content of fragments of caspase-cleaved cytokeratin-18 in the blood serum may be one of the informative indicators of non-alcoholic fatty liver disease progression.
The aim. To determine mechanisms of formation and progression of non-alcoholic fatty liver disease in obese children and adolescents by evaluating the level of cytokeratin-18.
Materials and methods. The study involved 46 adolescents with obesity and non-alcoholic fatty liver disease aged 12–17 years: 19 boys (41.3 %) and 27 girls (58.7 %). Clinical (weight, height, waist and hip circumference), laboratory (glucose, immunoreactive insulin, lipid metabolism, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, cytokeratin-18) parameters were studied and instrumental examination (abdominal ultrasound) was performed. To assess insulin resistance the triglyceride-glucose index was calculated.
Results. Depending on the presence of insulin resistance patients were divided into two groups: 21 (45.7 %) of adolescents with insulin resistance and 25 (54.3 %) of adolescents without insulin resistance. Blood tests in patients with insulin resistance revealed significantly higher levels of total cholesterol, triglycerides, very low-density lipoprotein cholesterol, fasting immunoreactive insulin, cytokeratin-18 and gamma-glutamyl transpeptidase. All adolescents were divided into 2 groups depending on the level of cytokeratin-18: patients with cytokeratin-18 >233 mIU/ml and <233 mIU/ml (15 (32.6 %) and 31 (67.4 %) respectively). It was found that there were significantly more patients with insulin resistance in the group with the level of cytokeratin-18 >233 mIU/ml.
Conclusion. In obese adolescents with non-alcoholic fatty liver disease insulin resistance is associated with more pronounced disorders of lipid and carbohydrate metabolism and higher levels of markers that characterize the state of the liver such as cytokeratin-18 and gamma-glutamyl transpeptidase. Adolescents with obesity and non-alcoholic fatty liver disease with a threshold level of cytokeratin-18, which indicates the transformation of steatosis into steatohepatitis, two times more often have present insulin resistance.
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Литература
Wittcopp, C., Conroy, R. (2016). Metabolic Syndrome in Children and Adolescents. Pediatrics in Review, 37 (5), 193–202. doi: http://doi.org/10.1542/pir.2014-0095
Bush, H., Golabi, P., Younossi, Z. M. (2017). Pediatric Non-Alcoholic Fatty Liver Disease. Children, 4 (6), 48. doi: http://doi.org/10.3390/children4060048
Anderson, E. L., Howe, L. D., Jones, H. E., Higgins, J. P. T., Lawlor, D. A., Fraser, A. (2015). The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLOS ONE, 10 (10), e0140908. doi: http://doi.org/10.1371/journal.pone.0140908
Mandelia, C., Kabbany, M. N., Conjeevaram Selvakumar, P. K., Alkhouri, N. (2018). The search for noninvasive methods to identify liver fibrosis in children with nonalcoholic fatty liver disease. Biomarkers in Medicine, 12 (3), 265–273. doi: http://doi.org/10.2217/bmm-2017-0038
Levy-Marchal, C., Arslanian, S., Cutfield, W., Sinaiko, A., Druet, C., Marcovecchio, M. L., Chiarelli, F. (2010). Insulin Resistance in Children: Consensus, Perspective, and Future Directions. The Journal of Clinical Endocrinology & Metabolism, 95 (12), 5189–5198. doi: http://doi.org/10.1210/jc.2010-1047
Tagi, V. M., Giannini, C., Chiarelli, F. (2019). Insulin Resistance in Children. Frontiers in Endocrinology, 10. doi: http://doi.org/10.3389/fendo.2019.00342
Singh, B. (2010). Surrogate markers of insulin resistance: A review. World Journal of Diabetes, 1 (2), 36. doi: http://doi.org/10.4239/wjd.v1.i2.36
Frithioff‐Bøjsøe, C., Lund, M. A. V., Lausten‐Thomsen, U., Hedley, P. L., Pedersen, O., Christiansen, M. et. al. (2019). Leptin, adiponectin, and their ratio as markers of insulin resistance and cardiometabolic risk in childhood obesity. Pediatric Diabetes, 21 (2), 194–202. doi: http://doi.org/10.1111/pedi.12964
Rodríguez-Morán, M., Simental-Mendía, L., Guerrero-Romero, F. (2017). The triglyceride and glucose index is useful for recognising insulin resistance in children. Acta Paediatrica, 106 (6), 979–983. doi: http://doi.org/10.1111/apa.13789
Alam, S., Mustafa, G., Alam, M., Ahmad, N. (2016). Insulin resistance in development and progression of nonalcoholic fatty liver disease. World Journal of Gastrointestinal Pathophysiology, 7 (2), 211. doi: http://doi.org/10.4291/wjgp.v7.i2.211
Strashok, L. A., Buznytska, O. V. (2019). Criteria for the progression of steatohepatosis in obese adolescents with signs of metabolic syndrome. CHILD`S HEALTH, 14 (6), 366–373. doi: http://doi.org/10.22141/2224-0551.14.6.2019.179244
Friedewald, W. T., Levy, R. I., Fredrickson, D. S. (1972). Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge. Clinical Chemistry, 18 (6), 499–502. doi: http://doi.org/10.1093/clinchem/18.6.499
Feldstein, A. E., Alkhouri, N., De Vito, R., Alisi, A., Lopez, R., Nobili, V. (2013). Serum Cytokeratin-18 Fragment Levels Are Useful Biomarkers for Nonalcoholic Steatohepatitis in Children. American Journal of Gastroenterology, 108 (9), 1526–1531. doi: http://doi.org/10.1038/ajg.2013.168
Khan, S. H., Sobia, F., Niazi, N. K., Manzoor, S. M., Fazal, N., Ahmad, F. (2018). Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetology & Metabolic Syndrome, 10 (1). doi: http://doi.org/10.1186/s13098-018-0376-8
Mohd Nor, N. S., Lee, S., Bacha, F., Tfayli, H., Arslanian, S. (2015). Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: comparison with the hyperinsulinemic-euglycemic clamp. Pediatric Diabetes, 17 (6), 458–465. doi: http://doi.org/10.1111/pedi.12303
Fiorentino, T. V., Marini, M. A., Succurro, E., Andreozzi, F., Sesti, G. (2019). Relationships of surrogate indexes of insulin resistance with insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and subclinical vascular damage. BMJ Open Diabetes Research & Care, 7 (1), e000911. doi: http://doi.org/10.1136/bmjdrc-2019-000911
Schwimmer, J. B., Deutsch, R., Rauch, J. B., Behling, C., Newbury, R., Lavine, J. E. (2003). Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. The Journal of Pediatrics, 143 (4), 500–505. doi: http://doi.org/10.1067/s0022-3476(03)00325-1
Calcaterra, V., Montalbano, C., de Silvestri, A., Pelizzo, G., Regalbuto, C., Paganelli, V. et. al. (2019). Triglyceride Glucose Index as a Surrogate Measure of Insulin Sensitivity in a Caucasian Pediatric Population. Journal of Clinical Research in Pediatric Endocrinology. doi: http://doi.org/10.4274/jcrpe.galenos.2019.2019.0024
Locateli, J. C., Lopes, W. A., Simões, C. F., de Oliveira, G. H., Oltramari, K., Bim, R. H. et. al. (2019). Triglyceride/glucose index is a reliable alternative marker for insulin resistance in South American overweight and obese children and adolescents. Journal of Pediatric Endocrinology and Metabolism, 32 (10), 1163–1170. doi: http://doi.org/10.1515/jpem-2019-0037
Neuman, M. G., Cohen, L. B., Nanau, R. M. (2014). Biomarkers in Nonalcoholic Fatty Liver Disease. Canadian Journal of Gastroenterology and Hepatology, 28 (11), 607–618. doi: http://doi.org/10.1155/2014/757929
He, L., Deng, L., Zhang, Q., Guo, J., Zhou, J., Song, W., Yuan, F. (2017). Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. BioMed Research International, 2017, 1–12. doi: http://doi.org/10.1155/2017/9729107
Fitzpatrick, E., Mitry, R. R., Quaglia, A., Hussain, M. J., deBruyne, R., Dhawan, A. (2010). Serum Levels of CK18 M30 and Leptin Are Useful Predictors of Steatohepatitis and Fibrosis in Paediatric NAFLD. Journal of Pediatric Gastroenterology and Nutrition, 51 (4), 500–506. doi: http://doi.org/10.1097/mpg.0b013e3181e376be
Lebensztejn, D. M., Wierzbicka, A., Socha, P., Pronicki, M., Skiba, E., Werpachowska, I., Kaczmarski, M. (2011). Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease. Acta Biochimica Polonica, 58 (4). doi: http://doi.org/10.18388/abp.2011_2225
Vuppalanchi, R., Jain, A. K., Deppe, R., Yates, K., Comerford, M., Masuoka, H. C. et. al. (2014). Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease. Clinical Gastroenterology and Hepatology, 12 (12), 2121–2130.e2. doi: http://doi.org/10.1016/j.cgh.2014.05.010
Vajro, P., Lenta, S., Socha, P., Dhawan, A., McKiernan, P., Baumann, U. et. al. (2012). Diagnosis of Nonalcoholic Fatty Liver Disease in Children and Adolescents. Journal of Pediatric Gastroenterology and Nutrition, 54 (5), 700–713. doi: http://doi.org/10.1097/mpg.0b013e318252a13f
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