title: Correlation between serum cytokeratin-18 and the progression or regression of non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Diagnosis of non-alcoholic fatty liver disease (NAFLD) is limited by the need for liver biopsies. Serum cytokeratin 18 (CK-18) levels have been investigated as potential biomarkers for the presence of NAFLD and non-alcoholic steatohepatitis (NASH). Herein, we assessed the correlation between CK-18 levels and NAFLD progression.
  
  
  METHODS
  Serum CK-18 levels were estimated using the M30 antibody enzyme-linked immunosorbent assay in 147 patients diagnosed with NAFLD. In 72 patients, disease progression was evaluated by repeated liver biopsy, which was conducted after 4.3 ± 2.6 years. The relationship between the CK-18 levels and liver histological findings was assessed.
  
  
  RESULTS
  The CK-18 levels were useful for identifying NAFLD patients with NAFLD activity scores (NAS) ≥ 5 (NAS ≥ 5 vs. ≤ 4: 675.1 U/L vs. 348.7 U/L; p < 0.0001). A cut-off value of 375 U/L was calculated using the receiver operating characteristic curve approach, with a specificity and sensitivity of 81.5 and 65%, respectively, for the diagnosis of NASH. Among the 72 patients who underwent repeated liver biopsy, 11 patients with a progressed NAS also had significantly increased serum CK-18 levels (p < 0.01); in 30 patients with an improved NAS, there was a significant improvement in the mean CK-18 levels (p < 0.0001). The 31 patients with static NAS had static CK-18 levels.
  
  
  CONCLUSIONS
  In conclusion, serum CK-18 levels can predict NAS ≥ 5 in NAFLD patients. In NAFLD patients, serum CK-18 levels reflect NAS values and correlate with histological changes, and they appear to be useful indicators of progression and improvement.
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Kawanaka
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishino
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Urata
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Suehiro
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawamoto
authors.affiliation: Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Gotaro
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D011237:Predictive Value of Tests; D012372:ROC Curve; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C488421:KRT18 protein, human; D053538:Keratin-18