title: Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Choosing endpoints in nonalcoholic steatohepatitis (NASH) trials is challenging because of the lack of validated surrogates and the trade-off between accuracy and invasiveness. In this study, we assessed diagnostic accuracy of serum aminotransferase changes in predicting histological changes in NASH trials.
  
  
  METHODS
  We conducted a longitudinal cohort study by using 102 participants in ursodeoxycholic acid-NASH trial who had both baseline and 2-year liver biopsy and multiple measurements of serum aminotransferases. We calculated rates of alanine aminotransferase (ALT) [or aspartate aminotransferase (AST)] change as slopes of linear regression over 2 years (IU/l/month) and changes in each histological feature as differences in Brunt's scores of two biopsies in each individual.
  
  
  RESULTS
  Rate of aminotransferase change correlated with changes in inflammation and fibrosis, but not steatosis and only with change in inflammation in multivariable analysis. In each histological feature, changes were inversely correlated with baseline histological grade. In predicting improvement of inflammation, areas under the receiver-operating characteristic curve of aminotransferase information alone were 0.72 for ALT and 0.73 for AST and were improved to 0.88 and 0.89, respectively, when baseline histology were taking account of.
  
  
  CONCLUSIONS
  Serum aminotransferase changes could be useful as surrogates in screening therapies for NASH in clinical trials with appropriate consideration of baseline aminotransferase and histology.
authors.affiliation: Gastroenterology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ayako
authors.initials: A
authors.lastname: Suzuki
authors.forename: James
authors.initials: J
authors.lastname: Lymp
authors.forename: Jenny
authors.initials: J
authors.lastname: St Sauver
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.forename: Keith
authors.initials: K
authors.lastname: Lindor
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015331:Cohort Studies; D005234:Fatty Liver / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase