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1. Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

Author

Stephanie Kelley, Manuel Lombardero, Shannon M. Riggs, Laurie A. Rodgers-Augustyniak, Sherry R. Hall, Jeffrey Teckman, Naureen Islam, Peter A. Lee, Karen F. Murray, Shirley Montanye, Jay H. Hoofnagle, Kathleen B. Schwarz, Kara Cooper, Rosemary A. Nagy, Daniel Cui, Norberto Rodriguez-Baez, Camille Langlois, Donna Stoliker, Natasha Feier, Tamara Haller, Douglas Mogul, Hejab Imteyaz, Frani Averbach, Robert A. Anders, Christina M. Lalama, Athena Hau, Andrew Pelesko, Hongxia Li, Qian Zhao, Kiyoko Oshima, Joel Feier, Sharon Lawlor, Jacki Cerkoski, Kim Kafka, Edward Doo, Melissa Weiner, Philip J. Rosenthal, Rebecca Torrance, Regina M. Hardison, Averell H. Sherker, Sarah Jane Schwarzenberg, Hsing-Hua S Lin, Ella Zadorozny, and Simon C. Ling

Subjects
Male, medicine.medical_specialty, Canada, Cirrhosis, Adolescent, Kaplan-Meier Estimate, Antiviral Agents, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatitis B, Chronic, 030225 pediatrics, Internal medicine, Medicine, Blood test, Humans, Decompensation, 030212 general & internal medicine, Prospective Studies, Practice Patterns, Physicians', Child, medicine.diagnostic_test, business.industry, Lamivudine, Infant, Entecavir, medicine.disease, United States, Treatment Outcome, Hepatocellular carcinoma, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Disease Progression, Female, business, Biomarkers, medicine.drug, Follow-Up Studies
Abstract

Objective To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. Study design This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. Results Among 362 children followed for a median of 4.2 years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. Conclusions In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.

Published
2020

2. 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

3. 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

4. Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

Author

Kathryn E. Harlow, Jonathan A. Africa, Alan Wells, Patricia H. Belt, Cynthia A. Behling, Ajay K. Jain, Jean P. Molleston, Kimberly P. Newton, Philip Rosenthal, Miriam B. Vos, Stavra A. Xanthakos, 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, Gerald Behr, Jay H. Lefkowitch, Ali Mencin, Elena Reynoso, Adina Alazraki, Rebecca Cleeton, Maria Cordero, Albert Hernandez, Saul Karpen, Jessica Cruz Munos, Nicholas Raviele, 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, Peter F. Whitington, Theresa Cattoor, Jose Derdoy, Janet Freebersyser, Debra King, Jinping Lai, Pat Osmack, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Susan S. Baker, Diana Lopez-Graham, Sonja Williams, Lixin Zhu, Hannah Awai, Craig Bross, Jennifer Collins, Janis Durelle, Michael Middleton, 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, Patrika Tsai, Kara Cooper, Simon Horslen, Evelyn Hsu, Karen Murray, Randolph Otto, Matthew Yeh, Melissa Young, Elizabeth M. Brunt, Kathryn Fowler, David E. Kleiner, Sherry Brown, Edward C. Doo, Jay H. Hoofnagle, Patricia R. Robuck, Averell Sherker, Rebecca Torrance, Jeanne M. Clark, Michele Donithan, Erin Hallinan, Milana Isaacson, Kevin P. May, Laura Miriel, Alice Sternberg, James Tonascia, Mark Van Natta, Laura Wilson, and Katherine Yates

Subjects
Male, medicine.medical_specialty, Statin, medicine.drug_class, Hypercholesterolemia, Article, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, 030225 pediatrics, Internal medicine, Intervention (counseling), Diabetes mellitus, Nonalcoholic fatty liver disease, Humans, Medicine, Longitudinal Studies, Child, Life Style, Triglycerides, Hypertriglyceridemia, business.industry, Cholesterol, LDL, medicine.disease, Diet, Clinical research, Pediatrics, Perinatology and Child Health, Female, 030211 gastroenterology & hepatology, business, Dietary modifications, Dyslipidemia
Abstract

OBJECTIVE:To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN:This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS:There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS:More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

Published
2018

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