Artigo Acesso aberto Revisado por pares

Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

2020; Elsevier BV; Volume: 159; Issue: 5 Linguagem: Inglês

10.1053/j.gastro.2020.07.034

ISSN

1528-0012

Autores

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 Scheimann, Tamir Miloh, Mark Fishbein, Cynthia Behling, Elizabeth M. Brunt, Arun J. Sanyal, James Tonascia, Stephanie H. Abrams, Donna Garner, Paula M. Hertel, Ryan Himes, Alicia Lawson, Tamir Miloh, Nicole Triggs, Kristin Bramlage, April Carr, Kim M. Cecil, Meghan McNeill, Marialena Mouzaki, Andrew T. Trout, Stavra A. Xanthakos, Kimberlee Bernstein, Stephanie DeVore, Rohit Kohli, Kathleen D. Lake, Daniel J. Podberesky, Alexander J. Towbin, Joel E. Lavine, Ali Mencin, Elena Reynoso, Adina Alazraki, Rebecca Cleeton, María Cordero, Albert Altés, Saul J. Karpen, Jessica Cruz Muños, Nicholas Raviele, Miriam B. Vos, Molly Bozic, Laura Carr, Oscar W. Cummings, Kathryn E. Harlow, Ann Klipsch, Jean P. Molleston, Emily Ragozzino, Girish S. Rao, Kimberly Kafka, Ann Scheimann, Mark Fishbein, Joy Ito, Saeed Mohammad, Peter F. Whitington, Sarah E. Barlow, Elizabeth M. Brunt, Danielle Carpenter, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Ajay K. Jain, Debra King, Jinping Lai, Joan Siegner, Susan D. 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, Joel E. Lavine, Michael S. Middleton, Kimberly P. Newton, Jeffrey B. Schwimmer, Claude B. Sirlin, Patricia Ugalde‐Nicalo, Jesse Courtier, Ryan M. Gill, Camille Langlois, Emily R. Perito, Philip Rosenthal, Patrika Tsai, Niviann Blondet, Kara Cooper, Karen F. Murray, Randolph K. Otto, Matthew M. Yeh, Melissa Young, Elizabeth M. Brunt, Kathryn J. Fowler, David E. Kleiner, Edward Doo, Sherry Hall, Jay H. Hoofnagle, Patricia R. Robuck, Averell H. Sherker, Rebecca Torrance, Patricia Belt, Jeanne M. Clark, J.A. Dodge, Michele Donithan, Milana Isaacson, Mariana Lazo, Jill Meinert, Laura Miriel, Emily P. Sharkey, Jacqueline Smith, Michael L. Smith, Jürgen Floege, James Tonascia, Mark L. Van Natta, Annette Wagoner, Laura Wilson, Goro Yamada, Katherine P. Yates,

Tópico(s)

Diet, Metabolism, and Disease

Resumo

Background & AimsNonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth.MethodsWe 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.ResultsAt 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 and/or in fibrosis was associated with adolescent age, and higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein cholesterol at baseline (<0.05), and over follow-up time, with increasing level of alanine aminotransferase, hemoglobin A1C (P<.05), gamma-glutamyl transferase and development of type 2 diabetes (P<.01). Increasing level of gamma-glutamyl transferase was also associated with reduced odds of any improvement (P = .003).ConclusionsOne-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. Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth. 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. 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 and/or in fibrosis was associated with adolescent age, and higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein cholesterol at baseline (<0.05), and over follow-up time, with increasing level of alanine aminotransferase, hemoglobin A1C (P<.05), gamma-glutamyl transferase and development of type 2 diabetes (P<.01). Increasing level of gamma-glutamyl transferase was also associated with reduced odds of any improvement (P = .003). 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.

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