1. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice
- Author
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Stavra A. Xanthakos, Joel E. Lavine, Katherine P. Yates, Jeffrey B. Schwimmer, Jean P. Molleston, Philip Rosenthal, Karen F. Murray, Miriam B. Vos, Ajay K. Jain, Ann O. Scheimann, Tamir Miloh, Mark Fishbein, Cynthia A. Behling, Elizabeth M. Brunt, Arun J. Sanyal, James Tonascia, Stephanie Abrams, Donna Garner, Paula Hertel, Ryan Himes, Alicia Lawson, 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, 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, Emily Ragozzino, Girish Rao, Kimberly Kafka, Ann Scheimann, Mark H. Fishbein, Joy Ito, Saeed Mohammad, Peter F. Whitington, Sarah Barlow, Danielle Carpenter, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Ajay Jain, Debra King, Jinping Lai, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Jorge Angeles, Jennifer Arin, Cynthia Behling, Craig Bross, Carissa Carrier, Jennifer Collins, Diana De La Pena, Janis Durelle, Mary Catherine Huckaby, Michael S. Middleton, Kimberly Newton, Claude Sirlin, Patricia Ugalde-Nicalo, Jesse Courtier, Ryan Gill, Camille Langlois, Emily Rothbaum Perito, Patrika Tsai, Niviann Blondet, Kara Cooper, Karen Murray, Randolph Otto, Matthew Yeh, Melissa Young, 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, Mark L. Van Natta, Annette Wagoner, Laura A. Wilson, and Goro Yamada
- Subjects
Blood Glucose ,Male ,0301 basic medicine ,Pediatric Obesity ,Time Factors ,Cirrhosis ,Biopsy ,Type 2 diabetes ,Chronic liver disease ,Severity of Illness Index ,Gastroenterology ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Nonalcoholic fatty liver disease ,Medicine ,Glucose homeostasis ,Prospective Studies ,Child ,Randomized Controlled Trials as Topic ,Fatty liver ,Age Factors ,Alanine Transaminase ,Treatment Outcome ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,medicine.medical_specialty ,Adolescent ,Risk Assessment ,digestive system ,Article ,03 medical and health sciences ,Internal medicine ,Humans ,Aspartate Aminotransferases ,Healthy Lifestyle ,Hepatology ,business.industry ,nutritional and metabolic diseases ,Odds ratio ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,business ,Risk Reduction Behavior ,Body mass index ,Biomarkers - Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth. METHODS: We compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8–17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis. RESULTS: At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH or in fibrosis occurred in 36% of the children, and both occurred in 11% of the children. Any improvement in NASH or fibrosis occurred in 52%, and both occurred in 20% of children. Type 2 diabetes developed in 5% of the cohort. Any progression to NASH and/or fibrosis was associated with adolescent age, higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein-cholesterol at baseline, increasing level of alanine aminotransferase, and hemoglobin A1C (P < .05). Progression to NASH and/or fibrosis were also associated with increasing level of gamma-glutamyl transferase and development of type 2 diabetes (P < .01). Increasing level of gamma-glutamyl transferase also associated with reduced odds of any improvement (P = .003). CONCLUSIONS: One-third of children with NAFLD enrolled in placebo groups of clinical trials had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.
- Published
- 2020
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