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BioMed Research International
Volume 2017, Article ID 9729107, 12 pages
https://doi.org/10.1155/2017/9729107
Review Article

Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

1Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Department of Laboratory Medicine, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, China
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4School of Medicine, Jianghan University, Wuhan, China

Correspondence should be addressed to Fahu Yuan; nc.ude.nuhj@hfnauy

Received 19 November 2016; Accepted 19 January 2017; Published 23 February 2017

Academic Editor: Kusum Kharbanda

Copyright © 2017 Lei He et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. Marchesini, E. Bugianesi, G. Forlani et al., “Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome,” Hepatology, vol. 37, no. 4, pp. 917–923, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. E. Fabbrini, S. Sullivan, and S. Klein, “Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications,” Hepatology, vol. 51, no. 2, pp. 679–689, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Chitturi, G. C. Farrell, and J. George, “Non-alcoholic steatohepatitis in the Asia-Pacific region: future shock?” Journal of Gastroenterology and Hepatology (Australia), vol. 19, no. 4, pp. 368–374, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. G. A. Michelotti, M. V. Machado, and A. M. Diehl, “NAFLD, NASH and liver cancer,” Nature Reviews Gastroenterology & Hepatology, vol. 10, no. 11, pp. 656–665, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. M. S. Ascha, I. A. Hanouneh, R. Lopez, T. A.-R. Tamimi, A. F. Feldstein, and N. N. Zein, “The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis,” Hepatology, vol. 51, no. 6, pp. 1972–1978, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Ertle, A. Dechêne, J.-P. Sowa et al., “Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis,” International Journal of Cancer, vol. 128, no. 10, pp. 2436–2443, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Wieckowska, A. J. McCullough, and A. E. Feldstein, “Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future,” Hepatology, vol. 46, no. 2, pp. 582–589, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. D. E. Amacher, “Progress in the search for circulating biomarkers of nonalcoholic fatty liver disease,” Biomarkers, vol. 19, no. 7, pp. 541–552, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Kwok, Y.-K. Tse, G. L.-H. Wong et al., “Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease—the role of transient elastography and plasma cytokeratin-18 fragments,” Alimentary Pharmacology and Therapeutics, vol. 39, no. 3, pp. 254–269, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Chen, Y. Y. Zhu, Q. Zheng, and J. J. Jiang, “Serum cytokeratin-18 in the diagnosis of non-alcoholic steatohepatitis: a meta-analysis,” Hepatology Research, vol. 44, no. 8, pp. 854–862, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Wieckowska, N. N. Zein, L. M. Yerian, A. R. Lopez, A. J. McCullough, and A. E. Feldstein, “In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease,” Hepatology, vol. 44, no. 1, pp. 27–33, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. Yilmaz, E. Dolar, E. Ulukaya et al., “Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis,” World Journal of Gastroenterology, vol. 13, no. 6, pp. 837–844, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. D. L. Diab, L. Yerian, P. Schauer et al., “Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients,” Clinical Gastroenterology and Hepatology, vol. 6, no. 11, pp. 1249–1254, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. A. E. Feldstein, A. Wieckowska, A. R. Lopez, Y.-C. Liu, N. N. Zein, and A. J. McCullough, “Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study,” Hepatology, vol. 50, no. 4, pp. 1072–1078, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. G. V. Papatheodoridis, E. Hadziyannis, E. Tsochatzis et al., “Serum apoptotic caspase activity in chronic hepatitis C and nonalcoholic fatty liver disease,” Journal of Clinical Gastroenterology, vol. 44, no. 4, pp. E87–E95, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Musso, R. Gambino, M. Durazzo, and M. Cassader, “Noninvasive assessment of liver disease severity with liver fat score and CK-18 in NAFLD: prognostic value of liver fat equation goes beyond hepatic fat estimation,” Hepatology, vol. 51, no. 2, pp. 715–717, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Malik, M. Chang, K. Bhaskar et al., “The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease,” Journal of Gastroenterology and Hepatology, vol. 24, no. 4, pp. 564–568, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Shen, H. L.-Y. Chan, G. L.-H. Wong et al., “Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers,” Alimentary Pharmacology & Therapeutics, vol. 36, no. 11-12, pp. 1057–1066, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. D. Joka, K. Wahl, S. Moeller et al., “Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis,” Hepatology, vol. 55, no. 2, pp. 455–464, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. Z. M. Younossi, M. Jarrar, C. Nugent et al., “A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH),” Obesity Surgery, vol. 18, no. 11, pp. 1430–1437, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. Z. M. Younossi, S. Page, N. Rafiq et al., “A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis,” Obesity Surgery, vol. 21, no. 4, pp. 431–439, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. I. Pirvulescu, L. Gheorghe, I. Csiki et al., “Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery,” Chirurgia (Bucharest, Romania : 1990), vol. 107, no. 6, pp. 772–779, 2012. View at Google Scholar · View at Scopus
  23. M. Grigorescu, D. Crisan, C. Radu, M. D. Grigorescu, Z. Sparchez, and A. Serban, “A novel pathophysiologicalbased panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis,” Journal of Physiology and Pharmacology, vol. 63, no. 4, pp. 347–353, 2012. View at Google Scholar · View at Scopus
  24. J. Y. Shen, H. L.-Y. Chan, G. L.-H. Wong et al., “Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers,” Journal of Hepatology, vol. 56, no. 6, pp. 1363–1370, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. Y. Yilmaz and F. Eren, “Identification of a support vector machine-based biomarker panel with high sensitivity and specificity for nonalcoholic steatohepatitis,” Clinica Chimica Acta, vol. 414, pp. 154–157, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Yang, D. Xu, Y. Liu et al., “Combined serum biomarkers in non-invasive diagnosis of non-alcoholic steatohepatitis,” PLOS ONE, vol. 10, no. 6, Article ID e0131664, 2015. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Yilmaz, F. Eren, O. Yonal et al., “Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease,” European Journal of Clinical Investigation, vol. 40, no. 10, pp. 887–892, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. H. T. Li, Q. C. Fang, F. Gao et al., “Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride,” Journal of Hepatology, vol. 53, no. 5, pp. 934–940, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Dushay, P. C. Chui, G. S. Gopalakrishnan et al., “Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease,” Gastroenterology, vol. 139, no. 2, pp. 456–463, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Dasarathy, Y. Yang, A. J. McCullough, S. Marczewski, C. Bennett, and S. C. Kalhan, “Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis,” European Journal of Gastroenterology & Hepatology, vol. 23, no. 5, pp. 382–388, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Reinehr, J. Woelfle, R. Wunsch, and C. L. Roth, “Fibroblast Growth Factor 21 (FGF-21) and its relation to obesity, metabolic syndrome, and nonalcoholic fatty liver in children: a longitudinal analysis,” Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 6, pp. 2143–2150, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. H. Li, K. Dong, Q. Fang 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,” Journal of Hepatology, vol. 58, no. 3, pp. 557–563, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Shen, X. Ma, J. Zhou et al., “Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease,” Cardiovascular Diabetology, vol. 12, no. 1, article 124, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Giannini, A. E. Feldstein, N. Santoro et al., “Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage,” Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 7, pp. 2993–3000, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Alisi, S. Ceccarelli, N. Panera et al., “Association between serum atypical fibroblast growth factors 21 and 19 and pediatric nonalcoholic fatty liver disease,” PLoS ONE, vol. 8, no. 6, Article ID e67160, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Panic, E. Leoncini, G. De Belvis, W. Ricciardi, and S. Boccia, “Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses,” PLOS ONE, vol. 8, no. 12, 2013. View at Publisher · View at Google Scholar · View at Scopus
  37. P. F. Whiting, A. W. S. Rutjes, M. E. Westwood et al., “Quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies,” Annals of Internal Medicine, vol. 155, no. 8, pp. 529–536, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. H. Sahai and A. Khurshid, “On analysis of epidemiological data involving a 2×2 contingency table: an overview of fisher's exact test and yates' correction for continuity,” Journal of Biopharmaceutical Statistics, vol. 5, no. 1, pp. 43–70, 1995. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Wree, L. Broderick, A. Canbay, H. M. Hoffman, and A. E. Feldstein, “From NAFLD to NASH to cirrhosis—new insights into disease mechanisms,” Nature Reviews Gastroenterology & Hepatology, vol. 10, no. 11, pp. 627–636, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. I. Nalbantoglu and E. M. Brunt, “Role of liver biopsy in nonalcoholic fatty liver disease,” World Journal of Gastroenterology, vol. 20, no. 27, pp. 9026–9037, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Bantel, P. Ruck, M. Gregor, and K. Schulze-Osthoff, “Detection of elevated caspase activation and early apoptosis in liver diseases,” European Journal of Cell Biology, vol. 80, no. 3, pp. 230–239, 2001. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. C. Woo, A. M. Xu, Y. Wang, and K. S. L. Lam, “Fibroblast Growth Factor 21 as an emerging metabolic regulator: clinical perspectives,” Clinical Endocrinology, vol. 78, no. 4, pp. 489–496, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. F. M. Fisher, P. C. Chui, P. J. Antonellis et al., “Obesity is a fibroblast growth factor 21 (FGF21)-resistant state,” Diabetes, vol. 59, no. 11, pp. 2781–2789, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Yan, M. Xia, X. Chang et al., “Circulating fibroblast growth factor 21 levels are closely associated with hepatic fat content: a cross-sectional study,” PLoS ONE, vol. 6, no. 9, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. G. C. Farrell and C. Z. Larter, “Nonalcoholic fatty liver disease: from steatosis to cirrhosis,” Hepatology, vol. 43, no. 2, pp. S99–S112, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Yilmaz, E. Ulukaya, and E. Dolar, “A 'biomarker biopsy' for the diagnosis of NASH: promises from CK-18 fragments,” Obesity Surgery, vol. 18, no. 11, pp. 1507–1508, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. P. Mofrad, M. J. Contos, M. Haque et al., “Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values,” Hepatology, vol. 37, no. 6, pp. 1286–1292, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. S. S. Kunde, A. J. Lazenby, R. H. Clements, and G. A. Abrams, “Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women,” Hepatology, vol. 42, no. 3, pp. 650–656, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. A. J. Sanyal, “Mechanisms of disease: pathogenesis of nonalcoholic fatty liver disease,” Nature Clinical Practice Gastroenterology and Hepatology, vol. 2, no. 1, pp. 46–53, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Hetz, K. Hoetzenecker, S. Hacker et al., “Caspase-cleaved cytokeratin 18 and 20 S proteasome in liver degeneration,” Journal of Clinical Laboratory Analysis, vol. 21, no. 5, pp. 277–281, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Wree, A. Kahraman, G. Gerken, and A. Canbay, “Obesity affects the liver—the link between adipocytes and hepatocytes,” Digestion, vol. 83, no. 1-2, pp. 124–133, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Wree, L. Broderick, A. Canbay, H. M. Hoffman, and A. E. Feldstein, “From NAFLD to NASH to cirrhosis-new insights into disease mechanisms,” Nature Reviews Gastroenterology and Hepatology, vol. 10, no. 11, pp. 627–636, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Wree, M. Schlattjan, L. P. Bechmann et al., “Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients,” Metabolism: Clinical and Experimental, vol. 63, no. 12, pp. 1542–1552, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Eusebi, “Diagnostic accuracy measures,” Cerebrovascular Diseases, vol. 36, no. 4, pp. 267–272, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Valva, E. De Matteo, M. C. Galoppo, M. I. Gismondi, and M. V. Preciado, “Apoptosis markers related to pathogenesis of pediatric chronic hepatitis C virus infection: M30 mirrors the severity of steatosis,” Journal of Medical Virology, vol. 82, no. 6, pp. 949–957, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Xu, D. J. Lloyd, C. Hale et al., “Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice,” Diabetes, vol. 58, no. 1, pp. 250–259, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Inagaki, P. Dutchak, G. Zhao et al., “Endocrine regulation of the fasting response by pparα-mediated induction of fibroblast growth factor 21,” Cell Metabolism, vol. 5, no. 6, pp. 415–425, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Y. Yu, F. Z. Xia, K. S. L. Lam et al., “Circadian rhythm of circulating fibroblast growth factor 21 is related to diurnal changes in fatty acids in humans,” Clinical Chemistry, vol. 57, no. 5, pp. 691–700, 2011. View at Publisher · View at Google Scholar · View at Scopus