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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 159; no. 5; pp. 1731 - 1751.e10
• Main Authors: Xanthakos, Stavra A., Lavine, Joel E., Schwimmer, Jeffrey B., Molleston, Jean P., Rosenthal, Philip, Murray, Karen F., Vos, Miriam B., Jain, Ajay K., Scheimann, Ann O., Fishbein, Mark, Brunt, Elizabeth M., Tonascia, James, Abrams, Stephanie, Garner, Donna, Hertel, Paula, Lawson, Alicia, Miloh, Tamir, Triggs, Nicole, Carr, April, Cecil, Kim, McNeill, Meghan, Mouzaki, Marialena, Bernstein, Kimberlee, DeVore, Stephanie, Kohli, Rohit, Lake, Kathleen, Towbin, Alex, Mencin, Ali, Reynoso, Elena, Alazraki, Adina, Cleeton, Rebecca, Cordero, Maria, Hernandez, Albert, Munos, Jessica Cruz, Raviele, Nicholas, Vos, Miriam, Carr, Laura, Cummings, Oscar W., Harlow, Kathryn, Klipsch, Ann, Ragozzino, Emily, Rao, Girish, Kafka, Kimberly, Scheimann, Ann, Fishbein, Mark H., Ito, Joy, Mohammad, Saeed, Barlow, Sarah, Cattoor, Theresa, Derdoy, Jose, Jain, Ajay, Siegner, Joan, Torretta, Susan, Angeles, Jorge, Arin, Jennifer, Behling, Cynthia, Bross, Craig, Carrier, Carissa, Collins, Jennifer, De La Pena, Diana, Huckaby, Mary Catherine, Middleton, Michael S., Newton, Kimberly, Sirlin, Claude, Ugalde-Nicalo, Patricia, Courtier, Jesse, Langlois, Camille, Perito, Emily Rothbaum, Tsai, Patrika, Cooper, Kara, Murray, Karen, Otto, Randolph, Yeh, Matthew, Young, Melissa, Fowler, Kathryn, Kleiner, David E., Doo, Edward C., Hall, Sherry, Hoofnagle, Jay H., Robuck, Patricia R., Sherker, Averell H., Torrance, Rebecca, Belt, Patricia, Dodge, John, Donithan, Michele, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Sharkey, Emily P., Smith, Jacqueline, Sternberg, Alice, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Yamada, Goro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Adolescent; Age Factors; Alanine Transaminase - blood; ALT; Aspartate Aminotransferases - blood; Biomarkers - blood; Biopsy; Blood Glucose - metabolism; Child; Cirrhosis; Diabetes Mellitus, Type 2 - epidemiology; Disease Progression; Female; Healthy Lifestyle; Histology; Humans; Male; Natural History; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - therapy; Pediatric Obesity - epidemiology; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Time Factors; Treatment Outcome; NAS; AST; NAFLD; OR; Natural History; CI; ALT; Histology; NASH; Cirrhosis; GGT; LDL; PNPLA3; HbA1c; NIDDK; NASH CRN; BMI
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2020.07.034

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.