Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-6bf8c574d5-qdpjg Total loading time: 0 Render date: 2025-03-01T07:33:44.596Z Has data issue: false hasContentIssue false

Chapter 36 - Non-Alcoholic Fatty Liver Disease in Children

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Rohit Kohli ,
Kevin E. Bove  and
Stavra A. Xanthakos
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
Get access

Summary

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in both adults and children worldwide [1]. Increasing industrialization and commercial globalization in Asia, South America, and the Middle East have led to shifts toward more western dietary habits and reduced energy expenditure, which, in turn, have increased the prevalence of overweight and obesity, and consequently NAFLD as a common cause of liver disease, even in developing economies [2].

Type
Chapter
Information
Liver Disease in Children , pp. 653 - 670
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Younossi, ZM, et al. Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64(1):73–84.CrossRefGoogle ScholarPubMed
Popkin, BM, Adair, LS, Ng, SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 2012;70(1):3–21.CrossRefGoogle ScholarPubMed
Semple, RK, et al. Genetic syndromes of severe insulin resistance. Endocr Rev 2011;32(4):498–514.CrossRefGoogle ScholarPubMed
Matteoni, CA, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116(6):1413–19.Google Scholar
Adams, LA, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129(1):113–21.Google Scholar
Goldberg, D, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology 2017;152(5):1090–9 e1.Google Scholar
Younossi, ZM, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation. Transplantation 2019;103(1):22–7.CrossRefGoogle ScholarPubMed
Shingina, A, et al. Future trends in demand for liver transplant: birth cohort effects among patients with NASH and HCC. Transplantation 2019;103(1):140–8.Google Scholar
Alkhouri, N, et al. Liver transplantation for nonalcoholic steatohepatitis in young patients. Transpl Int 2016;29(4):418–24.Google Scholar
Schwimmer, JB, et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006;118(4):1388–93.CrossRefGoogle ScholarPubMed
Browning, JD, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40(6):1387–95.CrossRefGoogle Scholar
Goyal, NP, Schwimmer, JB. The genetics of pediatric nonalcoholic fatty liver disease. Clin Liver Dis 2018;22(1):59–71.CrossRefGoogle ScholarPubMed
Anderson, EL, et al. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One 2015;10(10):e0140908.Google Scholar
Vos, MB, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017;64(2):319–34.Google Scholar
Schwimmer, JB, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138(4):1357–64, 1364 e1-2.CrossRefGoogle ScholarPubMed
Adeli, K. Closing the gaps in pediatric reference intervals: an update on the CALIPER project. Clin Biochem 2014;47(9):737–9.Google Scholar
Yu, EL, et al. Prevalence of nonalcoholic fatty liver disease in children with obesity. J Pediatr 2019;207:64–70.Google Scholar
Xanthakos, SA, et al. High prevalence of nonalcoholic fatty liver disease in adolescents undergoing bariatric surgery. Gastroenterology 2015;149(3):623–34 e8.Google Scholar
Manco, M, et al. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes 2008;32(2):381–7.Google Scholar
Manco, M, et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut 2008;57(9):1283–7.Google Scholar
Newton, KP, et al. Prevalence of prediabetes and type 2 diabetes in children with nonalcoholic fatty liver disease. JAMA Pediatr 2016;170(10):e161971.Google Scholar
Bhala, N, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54(4):1208–16.Google Scholar
Oliveira, S, et al. Incidental inflammatory adenoma with beta-catenin activation in the setting of paediatric NASH. Pediatr Obes 2018;13(1):70–3.Google Scholar
Kohli, R, et al. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr 2010;50(4):453–6.Google Scholar
Dunn, W, et al. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 2008;103(9):2263–71.Google Scholar
Ruhl, CE, Everhart, JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124(1):71–9.Google ScholarPubMed
Pacifico, L, et al. Functional and morphological vascular changes in pediatric nonalcoholic fatty liver disease. Hepatology 2010;52(5):1643–51.CrossRefGoogle ScholarPubMed
Caserta, CA, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol 2010;171(11):1195–202.CrossRefGoogle Scholar
Puri, P, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009;50(6):1827–38.Google Scholar
Kohli, R, et al. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology 2010;52(3):934–44.CrossRefGoogle Scholar
Nobili, V, et al. Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatr Res 2010;67(6):665–70.Google Scholar
Sanyal, AJ, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120(5):1183–92.CrossRefGoogle ScholarPubMed
Feldstein, AE, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003;125(2):437–43.Google Scholar
Kohli, R, et al. Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. J Biol Chem 2007;282(29):21327–36.Google Scholar
Sookoian, S, Pirola, CJ. Meta-analysis of the influence of I148 M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011;53(6):1883–94.Google Scholar
Santoro, N, et al. A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology 2010;52(4):1281–90.Google Scholar
Valenti, L, Alisi, A, Nobili, V. I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology. Hepatology 2012;56(2):1883–9.Google Scholar
Petersen, KF, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362(12):1082–9.Google Scholar
Al-Serri, A, et al. The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies. J Hepatol 2012;56(2):448–54.Google Scholar
Lin, YC, et al. Variants in the UGT1A1 gene and the risk of pediatric nonalcoholic fatty liver disease. Pediatrics 2009;124(6):e1221–7.CrossRefGoogle ScholarPubMed
Wattacheril, J, et al. Genome-wide associations related to hepatic histology in nonalcoholic fatty liver disease in Hispanic boys. J Pediatr 2017;190:100–7 e2.CrossRefGoogle ScholarPubMed
Abdelmalek, MF, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 2010;51(6):1961–71.Google Scholar
Welsh, JA, et al. Caloric sweetener consumption and dyslipidemia among US adults. JAMA 2010;303(15):1490–7.Google Scholar
Schwimmer, JB, et al. Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA 2019;321(3):256–65.Google Scholar
Schwimmer, JB, et al. Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with nonalcoholic fatty liver disease. Gastroenterology 2019;157(4):1109–22.Google Scholar
Frediani, JK, et al. Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005–2014. Environ Health 2018;17(1):6.CrossRefGoogle Scholar
Jin, R, et al. Perfluoroalkyl substances and severity of nonalcoholic fatty liver in children: an untargeted metabolomics approach. Environ Int 2020;134:105220.Google Scholar
Feldstein, AE, et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009;58(11):1538–44.Google Scholar
Barlow, SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007;120(Suppl 4):S164–92.Google Scholar
Lee, TH, et al. Serum aminotransferase activity and mortality risk in a United States community. Hepatology 2008;47(3):880–7.Google Scholar
Nobili, V, et al. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med 2009;7:21.Google Scholar
Patton, HM, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135(6):1961–71 e2.Google Scholar
Carter-Kent, C, et al. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009;50(4):1113–20.Google Scholar
Wieckowska, A, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44(1):27–33.Google Scholar
Vuppalanchi, R, et al. Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2014;12(12):2121–30 e1–2.Google Scholar
Alkhouri, N, et al. A combination of the pediatric NAFLD fibrosis index and enhanced liver fibrosis test identifies children with fibrosis. Clin Gastroenterol Hepatol 2011;9(2):150–5.CrossRefGoogle ScholarPubMed
Jackson, JA, et al. Performance of fibrosis prediction scores in paediatric non-alcoholic fatty liver disease. J Paediatr Child Health 2018;54(2):172–6.Google Scholar
Nobili, V, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008;48(2):442–8.Google Scholar
Schwimmer, JB, et al. Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease. Hepatology 2017;66(5):1474–85.Google Scholar
Sawh, MC, et al. Normal range for MR elastography measured liver stiffness in children without liver disease. J Magn Reson Imaging 2020;51(3):919–27.Google Scholar
Dillman, JR, et al. Quantitative liver MRI-biopsy correlation in pediatric and young adult patients with nonalcoholic fatty liver disease: can one be used to predict the other? AJR Am J Roentgenol 2018;210(1):166–74.Google Scholar
Mouzaki, M, et al. Assessment of nonalcoholic fatty liver disease progression in children using magnetic resonance imaging. J Pediatr 2018;201:86–92.CrossRefGoogle ScholarPubMed
Loomba, R, et al. Placebo in nonalcoholic steatohepatitis: insight into natural history and implications for future clinical trials. Clin Gastroenterol Hepatol 2008;6(11):1243–8.Google Scholar
Larson, SP, et al. Histopathologic variability between the right and left lobes of the liver in morbidly obese patients undergoing Roux-en-Y bypass. Clin Gastroenterol Hepatol 2007;5(11):1329–32.Google Scholar
Vos, MB, et al. Response to the letters regarding the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition NAFLD Guidelines. J Pediatr Gastroenterol Nutr 2017;65(5):e115–e116.Google Scholar
West, J, Card, TR. Reduced mortality rates following elective percutaneous liver biopsies. Gastroenterology 2010;139(4):1230–7.Google Scholar
Harwood, J, et al. Safety of blind percutaneous liver biopsy in obese children: a retrospective analysis. J Clin Gastroenterol 2010;44(10):e253–5.CrossRefGoogle ScholarPubMed
Brunt, EM, et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94(9):2467–74.CrossRefGoogle ScholarPubMed
Kleiner, DE, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–21.CrossRefGoogle ScholarPubMed
Musso, G, et al. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52(1):79–104.CrossRefGoogle ScholarPubMed
Nobili, V, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 2006;44(2):458–65.Google Scholar
Devore, S, et al. A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. J Pediatr Gastroenterol Nutr 2013;57(1):119–23.CrossRefGoogle ScholarPubMed
Nobili, V, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008;48(1):119–28.Google Scholar
Lavine, JE, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011;305(16):1659–68.Google Scholar
Sanyal, AJ, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362(18):1675–85.CrossRefGoogle ScholarPubMed
Klein, EA, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306(14):1549–56.Google Scholar
Schwimmer, JB, et al. In children with nonalcoholic fatty liver disease, cysteamine bitartrate delayed release improves liver enzymes but does not reduce disease activity scores. Gastroenterology 2016;151(6):1141–54 e9.Google Scholar
Inge, TH, Xanthakos, SA. Reversal of nonalcoholic steatohepatitis in adolescents after metabolic surgery. J Pediatr 2017;180:6–7.Google Scholar
Chavez-Tapia, NC, et al. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010;1:CD007340.Google Scholar
Manco, M, et al. The benefit of sleeve gastrectomy in obese adolescents on nonalcoholic steatohepatitis and hepatic fibrosis. J Pediatr 2017;180:31–7 e2.Google Scholar
Doycheva, I, et al. Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in young adults in the United States. J Clin Gastroenterol 2018;52(4):339–46.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×