Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis.
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.
Suzuki
Ayako
A
Gastroenterology, Duke University Medical Center, Durham, NC, USA.
Lymp
James
J
St Sauver
Jenny
J
Angulo
Paul
P
Lindor
Keith
K
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
D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase