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

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) wh...

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Published inGastroenterology (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
LanguageEnglish
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
Online AccessGet full text

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Abstract 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.
AbstractList 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.
Author Sternberg, Alice
Kohli, Rohit
Collins, Jennifer
Triggs, Nicole
Cattoor, Theresa
Hall, Sherry
Jain, Ajay K.
Karpen, Saul
Meinert, Jill
Carr, April
Jain, Ajay
Van Natta, Mark L.
Rosenthal, Philip
Sherker, Averell H.
Rao, Girish
Bozic, Molly
Scheimann, Ann O.
Yeh, Matthew
Munos, Jessica Cruz
Isaacson, Milana
Alazraki, Adina
Sirlin, Claude
Hoofnagle, Jay H.
Himes, Ryan
Torretta, Susan
Cooper, Kara
Tsai, Patrika
Harlow, Kathryn
Carr, Laura
Gill, Ryan
Wriston, Kristina
Perito, Emily Rothbaum
Langlois, Camille
Mohammad, Saeed
Cleeton, Rebecca
Schwimmer, Jeffrey B.
Young, Melissa
Siegner, Joan
Vos, Miriam B.
Lawson, Alicia
Fishbein, Mark H.
Arin, Jennifer
Clark, Jeanne M.
Brunt, Elizabeth M.
Behling, Cynthia A.
Stewart, Susan
Otto, Randolph
Raviele, Nicholas
Miriel, Laura
Carpenter, Danielle
Smith, Michael
Scheimann, Ann
Barlow, Sarah
Fowler, Kathryn
Newton, Kimberly
McNeill, Meghan
King, Debra
Carrier, Carissa
Blondet, Niviann
Xanthakos, Stavra A.
Whitington, Peter F.
Cordero, Maria
Trout, Andrew
Wilson, Laura A.
Bramlage, Kristin
DeVore, Stephanie
Lai, Jin
AuthorAffiliation 5 Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, Indiana
2 Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Columbia Vagelos College of Physicians and Surgeons, New York, New York
12 Department of Pediatrics, Feinberg Medical School of Northwestern University, Chicago, Illinois
9 Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, St. Louis University, St. Louis, Missouri
13 Department of Pathology, Sharp Memorial Hospital; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, California
11 Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, Florida
7 Pediatrics Institute, Cleveland Clinic Children’s, Cleveland, Ohio
3 Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
10 Johns Hopkins School of
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– name: 15 Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia
– name: 10 Johns Hopkins School of Medicine, Baltimore, Maryland
– name: 4 Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California
– name: 1 Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32712103$$D View this record in MEDLINE/PubMed
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Karpen, Saul
Carr, April
Jain, Ajay
Rosenthal, Philip
Rao, Girish
Bozic, Molly
Yeh, Matthew
Munos, Jessica Cruz
Isaacson, Milana
Alazraki, Adina
Sirlin, Claude
Himes, Ryan
Torretta, Susan
Cooper, Kara
Tsai, Patrika
Whitington, Peter F
Harlow, Kathryn
Carr, Laura
Gill, Ryan
Wriston, Kristina
Perito, Emily Rothbaum
Langlois, Camille
Mohammad, Saeed
Cleeton, Rebecca
Middleton, Michael S
Young, Melissa
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Lawson, Alicia
Arin, Jennifer
Stewart, Susan
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Raviele, Nicholas
Clark, Jeanne M
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Fowler, Kathryn
Newton, Kimberly
McNeill, Meghan
King, Debra
Carrier, Carissa
Blondet, Niviann
Cordero, Maria
Brunt, Elizabeth M
Fishbein, Mark H
Trout, Andrew
Bramlage, Kristin
DeVore, Stephanie
Lai, Jinping
Kafka, Kimberly
Cummings, Oscar W
Hernandez, Albert
Behling, Cynthia
Lake, Kathleen
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Molleston, Jean P
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Issue 5
Keywords NAS
AST
NAFLD
OR
Natural History
CI
ALT
Histology
NASH
Cirrhosis
GGT
LDL
PNPLA3
HbA1c
NIDDK
NASH CRN
BMI
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Snippet Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth. We compared...
BACKGROUND & AIMSNonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized...
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SubjectTerms 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
Title Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice
URI https://dx.doi.org/10.1053/j.gastro.2020.07.034
https://www.ncbi.nlm.nih.gov/pubmed/32712103
https://www.proquest.com/docview/2427522246
https://pubmed.ncbi.nlm.nih.gov/PMC7680281
Volume 159
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