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NASH |Abstract Library |
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Abstract Details |
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Alanine Aminotransferase and Gamma Glutamyl Transpeptidase Predict Histologic Improvement in Pediatric Nonalcoholic Steatohepatitis |
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Hepatology. 2020 May 16.doi: 10.1002/hep.31317. Online ahead of print.
Kimberly P Newton 1 2, Joel E Lavine 3, Laura Wilson 4 5, Cynthia Behling 6 7, Miriam B Vos 8, Jean P Molleston 9, Philip Rosenthal 10, Tamir Miloh 11, Mark H Fishbein 12, Ajay K Jain 13, Karen F Murray 14, Jeffrey B Schwimmer 1 2, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN):
Donna Garner, Paula Hertel, Ryan Himes, Alicia Lawson, Tamir Miloh, Nicole Triggs, Kristin Bramlage, April Carr, Kim Cecil, Meghan McNeill, Marialena Mouzaki, Andrew Trout, Stavra Xanthakos, Kimberlee Bernstein, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Daniel Podberesky, Alex Towbin, Joel E Lavine, Ali Mencin, Elena Reynoso, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Albert Hernandez, Saul Karpen, Jessica Cruz Munos, Nicholas Raviele, Miriam Vos, Molly Bozic, Laura Carr, Oscar W Cummings, Kathryn Harlow, Ann Klipsch, Jean P Molleston, Emily Ragozzino, Girish Rao, Kimberly Kafka, Ann Scheimann, Mark H Fishbein, Saeed Mohammad, Peter F Whitington, Sarah Barlow, Elizabeth M Brunt, Danielle Carpenter, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Ajay Jain Debra King, Jinping Lai, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Jennifer Arin, Cynthia Behling, Craig Bross, Carissa Carrier, Diana De La Pena, Janis Durelle, Mary Catherine Huckaby, Michael S Middleton, Kimberly Newton, Jeffrey B Schwimmer, Claude Sirlin, Patricia Ugalde-Nicalo, Jesse Courtier, Ryan Gill, Camille Langlois, Emily Rothbaum Perito, Philip Rosenthal, Patrika Tsai, Niviann Blondet, Kara Cooper, Karen Murray, Randolph Otto, Matthew Yeh, Melissa Young, Elizabeth M Brunt, Kathryn Fowler, David E Kleiner, Edward C Doo, Sherry Hall, Jay H Hoofnagle, Patricia R Robuck, Averell H Sherker, Rebecca Torrance, Patricia Belt, Jeanne M Clark, John Dodge, Michele Donithan, Milana Isaacson, Mariana Lazo, Jill Meinert, Laura Miriel, Emily P Sharkey, Jacqueline Smith, Michael Smith, Alice Sternberg, James Tonascia, Mark L Van Natta, Annette Wagoner, Laura A Wilson, Goro Yamada, Katherine P Yates
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Author information
- 1Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, USA.
- 2Department of Pediatrics, Division of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
- 3Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University, New York, NY, USA.
- 4Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
- 5Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
- 6Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
- 7Department of Pathology, Sharp Medical Center, San Diego, California, USA.
- 8Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
- 9Department of Pediatrics, Riley Children's Hospital, Indianapolis, IN, USA.
- 10Departments of Pediatrics & Surgery, University of California, San Francisco, United States.
- 11Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
- 12Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
- 13Department of Pediatrics, Saint Louis University, Saint Louis, United States.
- 14Department of Pediatrics, Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
Abstract
Predictive, non-invasive 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 clinical trial. This study included 146 children. Improvement in liver histology, defined as decrease in NAFLD Activity Score ≥ 2 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% (12/46). Multivariate models were constructed using baseline and change in ALT, AST, and GGT at 52 weeks, for improvement in 1) liver histology primary outcome 2) borderline zone 1 NASH, and 3) fibrosis. For improvement in histology, the model (p < 0.0001) retained baseline and change in GGT (AUROC 0.79; 95% CI 0.71 - 0.87). For borderline zone 1 NASH, the model (p = 0.0004) retained baseline and change in ALT (AUROC 0.80; 95% CI 0.67 - 0.93). For fibrosis, the model (p<0.001) retained baseline and change in ALT (AUROC 0.80, 95% CI 0.67-0.93). Additional clinical parameters were added to the models using Akaike's Information Criteria selection, and significantly boosted performance: improvement in histology with AUROC of 0.89 (95% CI 0.82 - 0.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI 0.83 - 0.99) and fibrosis with AUROC of 0.89 (95% CI 0.82-0.94). Models were validated using data from the TONIC trial. Conclusion: 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 histologic response.
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