Research Article
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Year 2025, Volume: 11 Issue: 2, 207 - 216
https://doi.org/10.18621/eurj.1619980

Abstract

References

  • 1. Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes (Lond). 2011;35(7):891-898. doi: 10.1038/ijo.2010.222.
  • 2. 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(10):e0140908. doi: 10.1371/journal.pone.0140908.
  • 3. Lenders CM, Gorman K, Lim-Miller A, Puklin S, Pratt J. Practical Approaches to the Treatment of Severe Pediatric Obesity. Pediatr Clin North Am. 2011;58(6):1425-1438. doi: 10.1016/j.pcl.2011.09.013.
  • 4. Yoneda M, Fujita K, Inamori M, Nakajima A, Tamano M, Hiraishi H. Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD). Gut. 2007;56(9):1330-1331. doi: 10.1136/gut.2007.126417.
  • 5. Liguori A, Ainora ME, Riccardi L, et al. The role of elastography in non-alcoholic fatty liver disease. Minerva Gastroenterol (Torino). 2021;67(2):164-170. doi: 10.23736/S2724-5985.21.02801-4.
  • 6. Feldstein AE, Wieckowska A, Lopez AR, Liu Y-C, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: A multicenter validation study. Hepatology. 2009;50(4):1072-1078. doi: 10.1002/hep.23050.
  • 7. Dushay J, Chui PC, Gopalakrishnan GS, et al. Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2010;139(2):456-463. doi: 10.1053/j.gastro.2010.04.054.
  • 8. Li H, Fang Q, Gao F, et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatol. 2010;53(5):934-940. doi: 10.1016/j.jhep.2010.05.018.
  • 9. Zhang X, Yeung DCY, Karpisek M, et al. Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans. Diabetes. 2008;57(5):1246-1253. doi: 10.2337/db07-1476.
  • 10. Christaki EV, Pervanidou P, Papassotiriou I, et al. Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship. Children. 2022;9(6). doi: 10.3390/children9060821.
  • 11. Baek J, Nam H-K, Rhie Y-J, Lee K-H. Serum FGF21 Levels in Obese Korean Children and Adolescents. J Obes Metab Syndr. 2017;26(3):204-209. doi: 10.7570/jomes.2017.26.3.204.
  • 12. Li G, Feng D, Qu X, et al. Role of adipokines FGF21, leptin and adiponectin in self-concept of youths with obesity. Eur Neuropsychopharmacol. 2018;28(8):892-902. doi: 10.1016/j.euroneuro.2018.05.015.
  • 13. El-Masry SA, Farid MN, Hassan NE, et al. Fibroblast growth factor-21 and Visfatin as potential predictors for metabolic risk factors in obese children. Sci Rep. 2024;14(1):1190. doi: 10.1038/s41598-024-51394-z.
  • 14. Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Ann Rev Physiol. 2016;78(1):223-241. doi: 10.1146/annurev-physiol-021115-105339.
  • 15. Dolegowska K, Marchelek-Mysliwiec M, Nowosiad-Magda M, Slawinski M, Dolegowska B. FGF19 subfamily members: FGF19 and FGF21. J Physiol Biochem. 2019;75(2):229-240. doi: 10.1007/s13105-019-00675-7.
  • 16. Rusli F, Deelen J, Andriyani E, et al. Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice. Sci Rep. 2016;6(1):30484. doi: 10.1038/srep30484.
  • 17. Shen FF, Lu LG. Advances in noninvasive methods for diagnosing nonalcoholic fatty liver disease. J Digest Dis. 2016;17(9):565-571. doi: 10.1111/1751-2980.12384.
  • 18. Giannini C, Feldstein AE, Santoro N, et al. Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage. J Clin Endocrinol Metab. 2013;98(7):2993-3000. doi: 10.1210/jc.2013-1250.
  • 19. Tucker B, McClelland RL, Allison MA, et al. Relationship of fibroblast growth factor 21 levels with inflammation, lipoproteins and non-alcoholic fatty liver disease. Atherosclerosis. 2020;299:38-44. doi: 10.1016/j.atherosclerosis.2020.03.009
  • 20. Li H, Dong K, Fang Q, et al. High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: A 3-year prospective study in China. J Hepatol. 2013;58(3):557-563. doi: 10.1016/j.jhep.2012.10.029.
  • 21. Falamarzi K, Malekpour M, Tafti MF, Azarpira N, Behboodi M, Zarei M. The role ofFGF21 and its analogs on liver associated diseases. Front Med (Lausanne). 2022;9:967375. doi: 10.3389/fmed.2022.967375.
  • 22. Hua M-C, Huang J-L, Hu C-C, Yao T-C, Lai M-W. Including Fibroblast Growth Factor-21 in Combined Biomarker Panels Improves Predictions of Liver Steatosis Severity in Children. Front Pediatr. 2019;7:420. doi: 10.3389/fped.2019.00420.
  • 23. Bantel H, Ruck P, Gregor M, Schulze-Osthoff K. Detection of elevated caspase activation and early apoptosis in liver diseases. Eur J Cell Biol. 2001;80(3):230-239. doi: 10.1078/0171-9335-00154.
  • 24. El Bassat H, Ziada DH, Hasby EA, Nagy H, Abo Ryia MH. Apoptotic and anti-apoptotic seromarkers for assessment of disease severity of non-alcoholic steatohepatitis. Arab J Gastroenterol. 2014;15(1):6-11. doi: 10.1016/j.ajg.2014.01.009.
  • 25. 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. doi: 10.1371/journal.pone.0082092.
  • 26. Alkhouri N, McCullough AJ. Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD. Gastroenterol Hepatol (N Y). 2012;8(10):661-668.
  • 27. Lebensztejn DM, Wierzbicka A, Socha P, et al. Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease. Acta Biochim Pol. 2011;58(4):563-566. doi: 10.18388/abp.2011_2225.
  • 28. Mandelia C, Collyer E, Mansoor S, et al. Plasma Cytokeratin‐18 Level As a Novel Biomarker for Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr. 2016;63(2):181-187. doi: 10.1097/MPG.0000000000001136.
  • 29. Koot BGP, van der Baan‐Slootweg OH, Bohte AE, et al. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity. 2013;21(3):583-590. doi: 10.1002/oby.20173.

The effect of obesity on FibroScan parameters, cytokeratin-18, and fibroblast growth factor-21 levels

Year 2025, Volume: 11 Issue: 2, 207 - 216
https://doi.org/10.18621/eurj.1619980

Abstract

Objectives: This study aimed to evaluate the differences in anthropometric, clinical, laboratory, and radiological parameters between obese and non-obese adolescents, focusing on the role of FibroScan parameters, Cytokeratin-18 (CK-18), and Fibroblast growth factor (FGF-21) in assessing metabolic and liver health.

Methods: Anthropometric data were collected, and blood pressure was measured. Laboratory parameters, including fasting glucose, insulin, HOMA-IR, liver enzymes, lipids, CK-18, and FGF-21 levels, were assessed. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were measured using Fibroscan. Pearson’s correlation analyses were performed to identify associations between CK-18/FGF-21 levels and metabolic parameters.

Results: A cross-sectional study involved 193 adolescents aged 10-18, including 87 obese and 106 non-obese participants. Obese adolescents had significantly higher fasting insulin, HOMA-IR, AST, ALT, GGT, uric acid, triglycerides, and LDL-cholesterol, with lower HDL-cholesterol levels (all P<0.001). CK-18 (P=0.05) and FGF-21 levels (P=0.002) were elevated in the obese group. CAP and LSM values were also significantly higher in obese participants (P<0.001). CK-18 and FGF-21 were positively correlated with fasting insulin, HOMA-IR, GGT, and triglycerides, indicating their potential as biomarkers for metabolic dysfunction. LSM correlated significantly with CK-18 (P=0.005) and FGF-21 (P=0.007).

Conclusions: Obese adolescents exhibited significant metabolic and liver dysfunction. Elevated CK-18 and FGF-21 levels, along with abnormal FibroScan parameters, highlight the importance of these biomarkers in identifying early liver injury and metabolic abnormalities. These findings suggest that CK-18 and FGF-21 may be valuable non-invasive tools for assessing and managing obesity-related liver disease.

Ethical Statement

The study received approval from the the Institutional Review Board (IRB) of the Ethics Committee of Konya Karatay University Faculty of Medicine (2021/19). Written informed consent was obtained from all participants and their guardians before enrollment.

References

  • 1. Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes (Lond). 2011;35(7):891-898. doi: 10.1038/ijo.2010.222.
  • 2. 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(10):e0140908. doi: 10.1371/journal.pone.0140908.
  • 3. Lenders CM, Gorman K, Lim-Miller A, Puklin S, Pratt J. Practical Approaches to the Treatment of Severe Pediatric Obesity. Pediatr Clin North Am. 2011;58(6):1425-1438. doi: 10.1016/j.pcl.2011.09.013.
  • 4. Yoneda M, Fujita K, Inamori M, Nakajima A, Tamano M, Hiraishi H. Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD). Gut. 2007;56(9):1330-1331. doi: 10.1136/gut.2007.126417.
  • 5. Liguori A, Ainora ME, Riccardi L, et al. The role of elastography in non-alcoholic fatty liver disease. Minerva Gastroenterol (Torino). 2021;67(2):164-170. doi: 10.23736/S2724-5985.21.02801-4.
  • 6. Feldstein AE, Wieckowska A, Lopez AR, Liu Y-C, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: A multicenter validation study. Hepatology. 2009;50(4):1072-1078. doi: 10.1002/hep.23050.
  • 7. Dushay J, Chui PC, Gopalakrishnan GS, et al. Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2010;139(2):456-463. doi: 10.1053/j.gastro.2010.04.054.
  • 8. Li H, Fang Q, Gao F, et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatol. 2010;53(5):934-940. doi: 10.1016/j.jhep.2010.05.018.
  • 9. Zhang X, Yeung DCY, Karpisek M, et al. Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans. Diabetes. 2008;57(5):1246-1253. doi: 10.2337/db07-1476.
  • 10. Christaki EV, Pervanidou P, Papassotiriou I, et al. Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship. Children. 2022;9(6). doi: 10.3390/children9060821.
  • 11. Baek J, Nam H-K, Rhie Y-J, Lee K-H. Serum FGF21 Levels in Obese Korean Children and Adolescents. J Obes Metab Syndr. 2017;26(3):204-209. doi: 10.7570/jomes.2017.26.3.204.
  • 12. Li G, Feng D, Qu X, et al. Role of adipokines FGF21, leptin and adiponectin in self-concept of youths with obesity. Eur Neuropsychopharmacol. 2018;28(8):892-902. doi: 10.1016/j.euroneuro.2018.05.015.
  • 13. El-Masry SA, Farid MN, Hassan NE, et al. Fibroblast growth factor-21 and Visfatin as potential predictors for metabolic risk factors in obese children. Sci Rep. 2024;14(1):1190. doi: 10.1038/s41598-024-51394-z.
  • 14. Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Ann Rev Physiol. 2016;78(1):223-241. doi: 10.1146/annurev-physiol-021115-105339.
  • 15. Dolegowska K, Marchelek-Mysliwiec M, Nowosiad-Magda M, Slawinski M, Dolegowska B. FGF19 subfamily members: FGF19 and FGF21. J Physiol Biochem. 2019;75(2):229-240. doi: 10.1007/s13105-019-00675-7.
  • 16. Rusli F, Deelen J, Andriyani E, et al. Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice. Sci Rep. 2016;6(1):30484. doi: 10.1038/srep30484.
  • 17. Shen FF, Lu LG. Advances in noninvasive methods for diagnosing nonalcoholic fatty liver disease. J Digest Dis. 2016;17(9):565-571. doi: 10.1111/1751-2980.12384.
  • 18. Giannini C, Feldstein AE, Santoro N, et al. Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage. J Clin Endocrinol Metab. 2013;98(7):2993-3000. doi: 10.1210/jc.2013-1250.
  • 19. Tucker B, McClelland RL, Allison MA, et al. Relationship of fibroblast growth factor 21 levels with inflammation, lipoproteins and non-alcoholic fatty liver disease. Atherosclerosis. 2020;299:38-44. doi: 10.1016/j.atherosclerosis.2020.03.009
  • 20. Li H, Dong K, Fang Q, et al. High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: A 3-year prospective study in China. J Hepatol. 2013;58(3):557-563. doi: 10.1016/j.jhep.2012.10.029.
  • 21. Falamarzi K, Malekpour M, Tafti MF, Azarpira N, Behboodi M, Zarei M. The role ofFGF21 and its analogs on liver associated diseases. Front Med (Lausanne). 2022;9:967375. doi: 10.3389/fmed.2022.967375.
  • 22. Hua M-C, Huang J-L, Hu C-C, Yao T-C, Lai M-W. Including Fibroblast Growth Factor-21 in Combined Biomarker Panels Improves Predictions of Liver Steatosis Severity in Children. Front Pediatr. 2019;7:420. doi: 10.3389/fped.2019.00420.
  • 23. Bantel H, Ruck P, Gregor M, Schulze-Osthoff K. Detection of elevated caspase activation and early apoptosis in liver diseases. Eur J Cell Biol. 2001;80(3):230-239. doi: 10.1078/0171-9335-00154.
  • 24. El Bassat H, Ziada DH, Hasby EA, Nagy H, Abo Ryia MH. Apoptotic and anti-apoptotic seromarkers for assessment of disease severity of non-alcoholic steatohepatitis. Arab J Gastroenterol. 2014;15(1):6-11. doi: 10.1016/j.ajg.2014.01.009.
  • 25. 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. doi: 10.1371/journal.pone.0082092.
  • 26. Alkhouri N, McCullough AJ. Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD. Gastroenterol Hepatol (N Y). 2012;8(10):661-668.
  • 27. Lebensztejn DM, Wierzbicka A, Socha P, et al. Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease. Acta Biochim Pol. 2011;58(4):563-566. doi: 10.18388/abp.2011_2225.
  • 28. Mandelia C, Collyer E, Mansoor S, et al. Plasma Cytokeratin‐18 Level As a Novel Biomarker for Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr. 2016;63(2):181-187. doi: 10.1097/MPG.0000000000001136.
  • 29. Koot BGP, van der Baan‐Slootweg OH, Bohte AE, et al. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity. 2013;21(3):583-590. doi: 10.1002/oby.20173.
There are 29 citations in total.

Details

Primary Language English
Subjects Gastroenterology and Hepatology
Journal Section Original Articles
Authors

Murat Keskin 0000-0003-4526-4352

Nizameddin Koca 0000-0003-1457-4366

Early Pub Date February 11, 2025
Publication Date
Submission Date January 14, 2025
Acceptance Date January 30, 2025
Published in Issue Year 2025 Volume: 11 Issue: 2

Cite

AMA Keskin M, Koca N. The effect of obesity on FibroScan parameters, cytokeratin-18, and fibroblast growth factor-21 levels. Eur Res J. 11(2):207-216. doi:10.18621/eurj.1619980

e-ISSN: 2149-3189 


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