title: Serum cytokeratin 18 fragment level as a noninvasive biomarker for non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Aida
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.affiliation: 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.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: 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.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagano
authors.affiliation: 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.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Seki
authors.affiliation: 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.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sugita
authors.affiliation: 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.
authors.forename: Munenori
authors.initials: M
authors.lastname: Itagaki
authors.affiliation: 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.
authors.forename: Haruya
authors.initials: H
authors.lastname: Ishiguro
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sutoh
authors.affiliation: 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.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Aizawa
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)