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1. Nutrition assessment and MASH severity in children using the Healthy Eating Index

Author

Jain, Ajay Kumar, Buchannan, Paula, Yates, Katherine P, Belt, Patricia, Schwimmer, Jeffrey B, Rosenthal, Philip, Murray, Karen F, Molleston, Jean P, Scheimann, Ann, Xanthakos, Stavra A, Behling, Cynthia A, Hertel, Paula, Nilson, Jamie, Neuschwander-Tetri, Brent A, Tonascia, James, Vos, Miriam B, Cavallo, Laurel, Garner, Donna, Hertel, Paula M, Mysore, Krupa R, Ortega, Taira Illescas, Tessier, Mary Elizabeth, Triggs, Nicole, Tsai, Cynthia, Arce-Clachar, Ana Catalina, Bramlage, Kristin, Cecil, Kim, Mouzaki, Marialena, Popelar, Ann, Trout, Andrew, Xanthakos, Stavra, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Dasarathy, Srinivasan, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Diehl, Anna Mae, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Alazraki, Adina, Garcia, Carmen, Jara-Garra, Jorge, Karpen, Saul, Vos, Miriam, Chalasani, Naga, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Adams, Kathryn Harlow, Jarasvaraparn, Chaowapong, Klipsch, Ann, Morlan, Wendy, Ragozzino, Emily, Samala, Niharika, Vuppalanchi, Raj, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Kowdley, Kris V, Liu, Kevin, Misic, Sandra, Sohal, Adam, Anthony, Angela, Chapin, Catherine, Fishbein, Mark H, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Jain, Ajay K, Ajmera, Veeral, Alba, Amy, Behling, Cynthia, Goyal, Nidhi, Keyvan, Leila, Loomba, Rohit, Madamba, Egbert, Middleton, Michael S, Morfin, Rebecca, Newton, Kimberly, Richards, Lisa, Singh, Seema, Sirlin, Claude, Skonieczny, Jaret, Ugalde-Nicalo, Patricia, Wang, Andrew, Awe, Remilekun, Gill, Ryan, Hameed, Bilal, Olvera, Daisy, and Terrault, Norah

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Obesity, Digestive Diseases, Nutrition, Prevention, Clinical Research, Clinical Trials and Supportive Activities, Pediatric, Oral and gastrointestinal, Metabolic and endocrine, Good Health and Well Being, Humans, Male, Child, Female, Diet, Healthy, Nutrition Assessment, Lipids, Sugars, Body Weight, Nonalcoholic Steatohepatitis Clinical Research Network, Clinical sciences
Abstract

BackgroundPediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.MethodsDiet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.ResultsIn all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index Z-score of 2.2 ± 0.5. Diet was classified as low HEI < 47.94 (n = 39), mid HEI ≥ 47.94 and < 58.89 (n = 41), or high HEI ≥ 58.89 (n=39). Children with high HEI (healthier diet) had lower body weight (p = 0.005) and more favorable lipids. Mean serum triglycerides for low, mid, and high HEI were 163, 148, and 120 mg/dL, respectively; p = 0.04 mid versus high, p = 0.01 low versus high. Mean HDL was 38, 41 and 43 mg/dL; p = 0.02 low vs high. Less severe steatosis was noted with added sugar ≤ 10% of calories (p = 0.03). Higher lobular inflammation is associated with a higher percentage of calories from fat (OR (95% CI) = 0.95 (0.91-1.00), p = 0.04).ConclusionsIn children with MAFLD, high HEI is associated with lower body weight and more favorable lipids, while added sugar and fat intake has individual histologic features. Differential consumption of major dietary components may modify both metabolic risk factors and histologic liver injury, highlighting the importance of objective diet assessments in children with MAFLD.

Published
2023

5. Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Author

Kimberly P. Newton, Laura A. Wilson, Nancy A. Crimmins, Mark H. Fishbein, Jean P. Molleston, Stavra A. Xanthakos, Cynthia Behling, Jeffrey B. Schwimmer, Donna Garner, Paula Hertel, Alicia Lawson, Yen Pham, Nicole Triggs, Kristin Bramlage, April Carr, Meghan McNeill, Marialena Mouzaki, Stavra Xanthakos, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Saul Karpen, Miriam Vos, Laura Carr, Oscar W. Cummings, Kathryn Harlow, Ann Klipsch, Wendy Morlan, Emily Ragozzino, Cindy Sawyers, Angela Anthony, Theresa Cattoor, Janet Freebersyser, Ajay K. Jain, Susan Torretta, Janis Durelle, Nidhi P. Goyal, Patricia Ugalde-Nicalo, Andrew Wang, Niviann Blondet, Kara Cooper, Randolph Otto, Matthew Yeh, Melissa Young, David E. Kleiner, Edward C. Doo, Sherry Hall, Jay H. Hoofnagle, Averell H. Sherker, Rebecca Torrance, Patricia R. Robuck, Peggy Adamo, Patricia Belt, Jeanne M. Clark, Jill Meinert, Laura Miriel, Carrie Shade, Emily P. Sharkey, Jacqueline Smith, Michael Smith, Alice Sternberg, ScM, James Tonascia, Mark L. Van Natta, Annette Wagoner, Tinsay Woreta, Katherine P. Yates, John Dodge, Michele Donithan, and Milana Isaacson

Subjects
Hepatology, Gastroenterology
Abstract

Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.

Published
2023
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6. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

Author

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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7. Low and High Birth Weights are Risk Factors for Nonalcoholic Fatty Liver Disease in Children

Author

Kimberly P. Newton, Haruna S. Feldman, Christina D. Chambers, Laura Wilson, Cynthia Behling, Jeanne M. Clark, Jean P. Molleston, Naga Chalasani, Arun J. Sanyal, Mark H. Fishbein, Joel E. Lavine, Jeffrey B. Schwimmer, Stephanie H. Abrams, Sarah Barlow, Ryan Himes, Rajesh Krisnamurthy, Leanel Maldonado, Rory Mahabir, April Carr, Kimberlee Bernstein, Kristin Bramlage, Kim Cecil, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Daniel Podberesky, Alex Towbin, Stavra Xanthakos, Daniela Allende, Srinivasan Dasarathy, Arthur J. McCullough, Mangesh Pagadala, Rish Pai, Cha'Ron Winston, Gerald Behr, Jay H. Lefkowitch, Ali Mencin, Elena Reynoso, Manal F. Abdelmalek, Mustafa Bashir, Stephanie Buie, Anna Mae Diehl, Cynthia Guy, Christopher Kigongo, David Malik, Yi-Ping Pan, Dawn Piercy, Mariko Kopping, Tyler Thrasher, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Albert Hernandez, Saul Karpen, Jessica Cruz Munos, Nicholas Raviele, Miriam Vos, Molly Bozic, Oscar W. Cummings, Samer Gawrieh, Ann Klipsch, Emily Ragozzino, Linda Ragozzino, Kumar Sandrasegaran, Girish Subbarao, Raj Vuppalanchi, Laura Walker, Kimberly Kafka, Ann Scheimann, Joy Ito, Saeed Mohammad, Cynthia Rigsby, Lisa Sharda, Peter F. Whitington, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Ajay Jain, Debra King, Jinping Lai, Pat Osmack, Joan Siegner, Susan Stewart, Brent A. Neuschwander-Tetri, Susan Torretta, Kristina Wriston, Fereshteh Assadian, Vanessa Barone, Maria Cardona Gonzalez, Jodie Davila, Oren Fix, Kelly Anne Hennessey, Kris V. Kowdley, Kacie Lopez, Erik Ness, Michelle Poitevin, Nicholas Procaccini, Brook Quist, Alana Saddic, Cara Wiseman, Matthew Yeh, Susan S. Baker, Diana Lopez-Graham, Sonja Williams, Lixin Zhu, Jonathan Africa, Brandon Ang, Hannah Awai, Archana Bhatt, Craig Bross, Jennifer Collins, Janis Durelle, Kathryn Harlow, Rohit Loomba, Michael Middleton, Kimberly Newton, Melissa Paiz, Claude Sirlin, Patricia Ugalde-Nicalo, Mariana Dominguez Villarreal, Bradley Aouizerat, Nathan M. Bass, Danielle Brandman, Jesse Courtier, Linda D. Ferrell, Natasha Feier, Ryan Gill, Bilal Hameed, Camille Langlois, Jacqueline Maher, Emily Rothbaum Perito, Claudia Ramos, Philip Rosenthal, Norah Terrault, Patrika Tsai, Ashley Ungermann, Pradeep Atla, Brandon Croft, Rebekah Garcia, Sonia Garcia, Muhammad Sheikh, Mandeep Singh, Kara Cooper, Simon Horslen, Evelyn Hsu, Karen Murray, Randolph Otto, Melissa Young, Sherry Boyett, Laura Carucci, Melissa J. Contos, Sherri Kirwin, Kenneth Kraft, Velimir A.C. Luketic, Puneet Puri, Jolene Schlosser, Mohammad S. Siddiqui, Elizabeth M. Brunt, Kathryn Fowler, David E. Kleiner, Sherry Brown, Edward C. Doo, Jay H. Hoofnagle, Patricia R. Robuck, Averell Sherker, Rebecca Torrance, Patricia Belt, Michele Donithan, Erin Hallinan, Milana Isaacson, Kevin P. May, Laura Miriel, Alice Sternberg, James Tonascia, Mark Van Natta, and Katherine Yates

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Databases, Factual, Cross-sectional study, Biopsy, Birth weight, Population, 030209 endocrinology & metabolism, Article, Infant, Postmature, Fetal Development, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Nonalcoholic fatty liver disease, Epidemiology, medicine, Birth Weight, Humans, education, Child, education.field_of_study, Obstetrics, business.industry, Infant, Low Birth Weight, medicine.disease, Obesity, United States, Low birth weight, Cross-Sectional Studies, 030104 developmental biology, Endocrinology, Liver, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Body mass index
Abstract

To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD.A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category.Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62).Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease.

Published
2017

8. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis

Author

Jonathan A. Africa, Cynthia A. Behling, Elizabeth M. Brunt, Nan Zhang, Yunjun Luo, Alan Wells, Jiayi Hou, Patricia H. Belt, Rohit Kohil, Joel E. Lavine, Jean P. Molleston, Kimberly P. Newton, Peter F. Whitington, Jeffrey B. Schwimmer, Stephanie H. Abrams, Sarah Barlow, Ryan Himes, Rajesh Krisnamurthy, Leanel Maldonado, Rory Mahabir, April Carr, Kimberlee Bernstein, Kristin Bramlage, Kim Cecil, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Daniel Podberesky, Alex Towbin, Stavra Xanthakos, Gerald Behr, Jay H. Lefkowitch, Ali Mencin, Elena Reynoso, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Albert Hernandez, Saul Karpen, Jessica Cruz Munos, Nicholas Raviele, Miriam Vos, Molly Bozic, Oscar W. Cummings, Ann Klipsch, Emily Ragozzino, Kumar Sandrasegaran, Girish Subbarao, Laura Walker, Kimberly Kafka, Ann Scheimann, Joy Ito, Mark H. Fishbein, Saeed Mohammad, Cynthia Rigsby, Lisa Sharda, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Ajay Jain, Debra King, Jinping Lai, Pat Osmack, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Susan S. Baker, Diana Lopez–Graham, Sonja Williams, Lixin Zhu, Jonathan Africa, Hannah Awai, Cynthia Behling, Craig Bross, Jennifer Collins, Janis Durelle, Kathryn Harlow, Michael Middleton, Kimberly Newton, Melissa Paiz, Claude Sirlin, Patricia Ugalde-Nicalo, Mariana Dominguez Villarreal, Bradley Aouizerat, Jesse Courtier, Linda D. Ferrell, Natasha Feier, Ryan Gill, Camille Langlois, Emily Rothbaum Perito, Philip Rosenthal, Patrika Tsai, Kara Cooper, Simon Horslen, Evelyn Hsu, Karen Murray, Randolph Otto, Matthew Yeh, Melissa Young, and Kathryn Fowler

Subjects
0301 basic medicine, Liver Cirrhosis, Male, medicine.medical_specialty, Adolescent, Biopsy, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Child, Hepatology, business.industry, Histocytochemistry, nutritional and metabolic diseases, Baseline data, medicine.disease, Fibrosis, Response to treatment, Obesity, Hepatitis C, digestive system diseases, Advanced fibrosis, Fatty Liver, 030104 developmental biology, Cross-Sectional Studies, Liver, Disease Progression, 030211 gastroenterology & hepatology, Female, Steatosis, Steatohepatitis, business, Body mass index
Abstract

BACKGROUND & AIMS: Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. METHODS: We performed a cross-sectional study of baseline data from 813 children (age less than 18 years; mean age, 12.8±2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the NASH Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. RESULTS: Zone 1 steatosis was present in 18% of children with NAFLD (n=146) and zone 3 steatosis was present in 32% (n=244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P

Published
2016

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