{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:07:55Z","timestamp":1789416475648,"version":"build-2803163510"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Predictive, noninvasive tools are needed to monitor key features of nonalcoholic fatty liver disease (NAFLD) in children that relate to improvement in liver histology. The purpose of this study was to evaluate the relationship between liver chemistries and liver histology using data from the CyNCh (Cysteamine Bitartrate Delayed\u2010Release for the Treatment of NAFLD in Children) clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      This study included 146 children. Improvement in liver histology, defined as decrease in nonalcoholic fatty liver disease (NAFLD) Activity Score \u22652 points without worsening of fibrosis, occurred in 43 participants (30%). There were 46 participants with borderline zone 1 nonalcoholic steatohepatitis (NASH) at baseline, with resolution in 28% (12 of 46). Multivariate models were constructed using baseline and change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma\u2010glutamyl transferase (GGT) at 52\u00a0weeks, for improvement in (1) liver histology primary outcome, (2) borderline zone 1 NASH, and (3) fibrosis. For improvement in histology, the model (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) retained baseline and change in GGT (area under the receiver operating characteristic [AUROC], 0.79; 95% confidence interval [CI], 0.71\u20100.87). For borderline zone 1 NASH, the model (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a00.0004) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67\u20100.93). For fibrosis, the model (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67\u20100.93). Additional clinical parameters were added to the models using Akaike\u2019s information criterion selection, and significantly boosted performance: improvement in histology with AUROC of 0.89 (95% CI, 0.82\u20100.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI, 0.83\u20100.99), and fibrosis with AUROC of 0.89 (95% CI, 0.82\u20100.94). Models were validated using data from the TONIC (Treatment of Nonalcoholic Fatty Liver Disease in Children) trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In children with NAFLD, dynamic changes in serum ALT and GGT are associated with change in liver histology and appear to be powerful indicators of histological response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31317","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T18:44:12Z","timestamp":1589654652000},"page":"937-951","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":63,"title":["Alanine Aminotransferase and Gamma\u2010Glutamyl Transpeptidase Predict Histologic Improvement in Pediatric Nonalcoholic Steatohepatitis"],"prefix":"10.1097","volume":"73","author":[{"given":"Kimberly P.","family":"Newton","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,University of California San Diego School of Medicine,La Jolla,CA"},{"name":"Division of Gastroenterology,Department of Pediatrics,Rady Children\u2019s Hospital,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel E.","family":"Lavine","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition,Department of Pediatrics,Columbia University,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD"},{"name":"Department of Medicine,Johns Hopkins University,School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Behling","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,University of California San Diego School of Medicine,La Jolla,CA"},{"name":"Department of Pathology,Sharp Medical Center,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam B.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Emory University School of Medicine and Children\u2019s Healthcare of Atlanta,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean P.","family":"Molleston","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Riley Children\u2019s Hospital,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics & Surgery,University of California,San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamir","family":"Miloh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Texas Children's Hospital,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Fishbein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Ann & Robert H. Lurie Children\u2019s Hospital of Chicago,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Saint Louis University,St. Louis,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen F.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Cleveland Clinic Children\u2019s Hospital,Cleveland,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Schwimmer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,University of California San Diego School of Medicine,La Jolla,CA"},{"name":"Division of Gastroenterology,Department of Pediatrics,Rady Children\u2019s Hospital,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Nonalcoholic Steatohepatitis Clinical Research Network 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