title: Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population.
abstract: Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH.
  
  
  OBJECTIVE
  To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population.
  
  
  METHODS
  Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test.
  
  
  RESULTS
  The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61).
  
  
  CONCLUSIONS
  CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Arab
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Cristián
authors.initials: C
authors.lastname: Hernández-Rocha
authors.affiliation: Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Morales
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Vargas
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Nancy
authors.initials: N
authors.lastname: Solís
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.affiliation: Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Camila
authors.initials: C
authors.lastname: Robles
authors.affiliation: Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sandoval
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Simon
authors.initials: S
authors.lastname: Ponthus
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Benítez
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barrera
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soza
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Riquelme
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: marrese@med.puc.cl.
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002677:Chile / Q000453:epidemiology; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D010446:Peptide Fragments
keywords: Citoqueratina-18; Cytokeratin-18; Esteatohepatitis; Esteatosis; Fatty liver; Hígado graso; No invasivo; Non-invasive; Steatohepatitis; Steatosis