Int J Clin Exp Med. 2014 Nov 15;7(11):4191-8. eCollection 2014.
Serum cytokeratin 18 fragment level as a noninvasive biomarker for non-alcoholic fatty liver disease.
International journal of clinical and experimental medicine
Yuta Aida, Hiroshi Abe, Yoichi Tomita, Tomohisa Nagano, Nobuyoshi Seki, Tomonori Sugita, Munenori Itagaki, Haruya Ishiguro, Satoshi Sutoh, Yoshio Aizawa
Affiliations
Affiliations
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Jikei University School of Medicine, Katsushika Medical Center 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
PMID: 25550930
PMCID: PMC4276188
Abstract
BACKGROUND AND AIM: We evaluated the usefulness of serum cytokeratin 18 fragment (CK18-F) as a noninvasive biomarker in differentiating nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) since the prognosis of the 2 diseases differ.
METHODS: 116 Japanese patients with nonalcoholic fatty liver disease (NAFLD) proven by liver biopsy were studied. Histological findings were classified according to the NAFLD activity score (NAS) proposed by the Nonalcoholic Steatohepatitis Clinical Research Network. The correlation between histological findings and serum CK18-F levels was investigated.
RESULTS: Serum CK18-F levels showed a positive correlation with histologic steatosis (ρ = 0.271, P = 0.0033), inflammation (ρ = 0.353, P = 0.0005), ballooning (ρ = 0.372, P = 0.0001), and the total NAS (ρ = 0.474, P = 2.68 × 10-7). The serum CK18-F level was significantly lower for NAFL (NAS ≤ 2) than for borderline NASH (NAS of 3-4) or definite NASH (NAS ≥ 5) (P = 0.0294, P = 1.163 × 10-5, respectively). The serum CK18-F level was significantly higher for definite NASH than for borderline NASH (P = 0.0002). The area under the receiver operating characteristic curve of serum CK18-F to predict the presence of NAFL and definite NASH was 0.762 and 0.757, respectively. The optimal cut-off point of serum CK18-F for NAFL and definite NASH was 230 and 270 U/L, respectively. The sensitivity, specificity, positive predict value, and negative predict value of serum CK18-F for NAFL were 0.89, 0.65, 0.34, and 0.97, and those for definite NASH were 0.64, 0.76, 0.72, and 0.67, respectively. Accuracies of diagnosis for both NAFL and definite NASH were 0.70.
CONCLUSIONS: Serum CK18-F could be a clinically useful biomarker to discriminate between NAFL and NASH.
Keywords: Nonalcoholic fatty liver disease (NAFLD); definite nonalcoholic steatohepatitis (NASH); nonalcoholic fatty liver (NAFL); nonalcoholic fatty liver disease activity score (NAS); serum cytokeratin 18 fragment (CK18-F)
References
- Clin Chem. 1972 Jun;18(6):499-502 - PubMed
- Gut. 2008 Oct;57(10):1441-7 - PubMed
- Hepatol Res. 2007 Sep;37(9):722-30 - PubMed
- Hepatology. 2002 Oct;36(4 Pt 1):986-92 - PubMed
- Ann Epidemiol. 2007 Nov;17(11):863-9 - PubMed
- Hepatology. 2011 Mar;53(3):810-20 - PubMed
- Liver Int. 2006 Oct;26(8):956-63 - PubMed
- World J Gastroenterol. 2007 Feb 14;13(6):837-44 - PubMed
- Hepatology. 2007 Apr;45(4):846-54 - PubMed
- J Gastroenterol. 2003;38(10):954-61 - PubMed
- Dig Liver Dis. 2008 May;40(5):371-8 - PubMed
- Gastroenterology. 2001 Sep;121(3):710-23 - PubMed
- Hepatology. 2006 Jun;43(6):1317-25 - PubMed
- BMC Gastroenterol. 2006 Nov 02;6:33 - PubMed
- Hepatology. 2004 Nov;40(5):1078-87 - PubMed
- J Hepatol. 2013 Oct;59(4):859-71 - PubMed
- Cell Death Differ. 2007 Jul;14(7):1237-43 - PubMed
- Hepatology. 2003 Aug;38(2):518-26 - PubMed
- Gastroenterology. 2009 Sep;137(3):865-72 - PubMed
- J Clin Gastroenterol. 2010 Apr;44(4):e87-95 - PubMed
- Gastroenterology. 2003 Aug;125(2):437-43 - PubMed
- Gastroenterology. 1999 Jun;116(6):1413-9 - PubMed
- J Hepatol. 2002 Jul;37(1):154-60 - PubMed
- Hepatology. 2004 Dec;40(6):1387-95 - PubMed
- Hepatology. 2006 Jul;44(1):27-33 - PubMed
- J Gastroenterol Hepatol. 2009 Apr;24(4):564-8 - PubMed
- Dig Dis Sci. 2013 Jan;58(1):265-74 - PubMed
- J Hepatol. 2014 Jan;60(1):167-74 - PubMed
- Lancet. 2004 Jan 10;363(9403):157-63 - PubMed
- Hepatol Res. 2014 Aug;44(8):827-8 - PubMed
- Diabetes Care. 2000 Jan;23(1):57-63 - PubMed
- J Gastroenterol. 2006 Aug;41(8):725-32 - PubMed
- J Clin Gastroenterol. 2010 Jul;44(6):440-7 - PubMed
- Aliment Pharmacol Ther. 2012 Dec;36(11-12):1057-66 - PubMed
- Clin Gastroenterol Hepatol. 2012 Oct;10(10):1162-8; quiz e87 - PubMed
- Hepatology. 2012 Jun;55(6):2005-23 - PubMed
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