title: Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease.
abstract: Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87.
  
  
  CONCLUSIONS
  PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH.
authors.affiliation: UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, UK. Sudeep.Tanwar@nhs.net
authors.forename: Sudeep
authors.initials: S
authors.lastname: Tanwar
authors.forename: Paul M
authors.initials: PM
authors.lastname: Trembling
authors.forename: Indra N
authors.initials: IN
authors.lastname: Guha
authors.forename: Julie
authors.initials: J
authors.lastname: Parkes
authors.forename: Philip
authors.initials: P
authors.lastname: Kaye
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Burt
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ryder
authors.forename: Guruprasad P
authors.initials: GP
authors.lastname: Aithal
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.forename: William M
authors.initials: WM
authors.lastname: Rosenberg
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D024141:Collagen Type IV / Q000097:blood; D005234:Fatty Liver / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005355:Fibrosis; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D053538:Keratin-18 / Q000097:blood; D037102:Lectins / Q000097:blood; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D024141:Collagen Type IV; C488421:KRT18 protein, human; D053538:Keratin-18; D037102:Lectins; D010446:Peptide Fragments; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid