Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-09T14:34:16.178Z 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:  05 March 2014

Rohit Kohli
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati Children’s Steatohepatitis Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Kevin E. Bove
Affiliation:
Division of Pediatric Pathology, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Stavra A. Xanthakos
Affiliation:
Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Frederick J. Suchy
Affiliation:
University of Colorado Medical Center
Ronald J. Sokol
Affiliation:
University of Colorado Medical Center
William F. Balistreri
Affiliation:
University of Cincinnati College of Medicine
Get access

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common cause of liver disease in both adults and children in the USA because of its strong association with the epidemic rates of obesity across all age groups. Originally considered predominantly to be a disease of developed countries with affluent and sedentary lifestyles, NAFLD has emerged in the last decade as a significant cause of liver disease worldwide, even in developing economies [1]. Increasing industrialization and commercial globalization in Asia, South America, and the Middle East have led to significant population shifts toward more western dietary habits and reduced energy expenditure, which, in turn, have increased the prevalence of overweight and obesity, and led to the identification of NAFLD as a common cause of liver disease [2].

While diverse conditions can lead to abnormal hepatic steatosis, defined as steatosis in >5% of hepatocytes, NAFLD is predominantly associated with excess adiposity, in particular central adiposity, and occurs in the absence of significant alcohol intake. It can be found in lean individuals but typically they too have significant visceral adiposity or severe insulin resistance syndromes, such as lipodystrophy [3].

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2014

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

Das, K, Mukherjee, PS, Ghosh, A, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593–1602.CrossRefGoogle Scholar
Popkin, BM, Adair, LS, Ng, SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 2012;70:3–21.CrossRefGoogle ScholarPubMed
Semple, RK, Savage, DB, Cochran, EK, Gorden, P, O’Rahilly, S. Genetic syndromes of severe insulin resistance. Endocr Rev 2011;32:498–514.CrossRefGoogle ScholarPubMed
Matteoni, CA, Younossi, ZM, Gramlich, T, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413–1419.CrossRefGoogle ScholarPubMed
Adams, LA, Lymp, JF, Sauver, ST, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129:113–121.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Deutsch, R, Kahen, T, et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006;118:1388–1393.CrossRefGoogle ScholarPubMed
Browning, JD, Szczepaniak, LS, Dobbins, R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.CrossRefGoogle Scholar
Fraser, A, Longnecker, MP, Lawlor, DA. Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999–2004. Gastroenterology 2007;133:1814–1820.CrossRefGoogle ScholarPubMed
Strauss, RS, Barlow, SE, Dietz, WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr 2000;136:727–733.Google ScholarPubMed
Alavian, SM, Mohammad-Alizadeh, AH, Esna-Ashari, F, Ardalan, G, Hajarizadeh, B. Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int 2009;29:159–163.CrossRefGoogle ScholarPubMed
Park, HS, Han, JH, Choi, KM, Kim, SM. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr 2005;82:1046–1051.CrossRefGoogle ScholarPubMed
Tominaga, K, Kurata, J, Chen, Y, et al. Prevalence of fatty liver in Japanese children and relationship to obesity: an epidemiological ultrasonographic survey. Dig Dis Sci 1995;40:2002–2209.CrossRefGoogle Scholar
Meng, L, Luo, N, Mi, J. Impacts of types and degree of obesity on non-alcoholic fatty liver disease and related dyslipidemia in Chinese school-age children? Biomed Environ Sci 2011;24:22–30.Google ScholarPubMed
Booth, ML, George, J, Denney-Wilson, E, et al. The population prevalence of adverse concentrations and associations with adiposity of liver tests among Australian adolescents. J Paediatr Child Health 2008;44:686–691.CrossRefGoogle ScholarPubMed
Manco, M, Marcellini, M, Devito, R, et al. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes 2008;32:381–387.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Dunn, W, Norman, GJ, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138:1357–1364.CrossRefGoogle ScholarPubMed
Kunde, SS, Lazenby, AJ, Clements, RH, Abrams, GA, et al. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology 2005;42:650–656.CrossRefGoogle ScholarPubMed
Xanthakos, S, Miles, L, Bucuvalas, J, et al. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clin Gastroenterol Hepatol 2006;4:226–232.CrossRefGoogle ScholarPubMed
Manco, M, Bedogni, G, Marcellini, M, et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut 2008;57:1283–1287.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Deutsch, R, Rauch, JB, et al. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 2003;143:500–505.CrossRefGoogle ScholarPubMed
Bhala, N, Angulo, P, van der Poorten, D, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54:1208–1216.CrossRefGoogle ScholarPubMed
Ascha, MS, Hanouneh, IA, Lopez, R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972–1978.CrossRefGoogle ScholarPubMed
Kohli, R, Boyd, T, Lake, K, et al. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr 2010;50:453–456.Google ScholarPubMed
Feldstein, AE, Treeprasertsuk, S, Sharatcharoenwitthay, AP, et al. The natural history of nonalchololic fatty liver disease in children: a follow-up study for up to 20 years. Hepatology 2008;48(Suppl):335A.Google Scholar
Dunn, W, Xu, R, Wingard, DL, et al. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterology 2008;103:2263–2271.CrossRefGoogle Scholar
Ruhl, CE, Everhart, JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124:71–79.CrossRefGoogle ScholarPubMed
Pacifico, L, Anania, C, Martino, F, et al. Functional and morphological vascular changes in pediatric nonalcoholic fatty liver disease. Hepatology 2010;52:1643–1651.CrossRefGoogle ScholarPubMed
Caserta, CA, Pendino, GM, Amante, A, 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;171:1195–1202.CrossRefGoogle Scholar
Puri, P, Wiest, MM, Cheung, O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009;50:1827–1838.CrossRefGoogle ScholarPubMed
Kohli, R, Kirby, M, Xanthakos, SA, 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;52:934–944.CrossRefGoogle Scholar
Nobili, V, Alkhouri, N, Bartuli, A, et al. Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatr Res 2010;67:665–670.CrossRefGoogle ScholarPubMed
Sanyal, AJ, Campbell-Sargent, C, Mirshahi, F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183–1192.CrossRefGoogle ScholarPubMed
Feldstein, AE, Canbay, A, Angulo, P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003;125:437–443.CrossRefGoogle ScholarPubMed
Kohli, R, Pan, X, Malladi, P, Wainwright, MS, Whitington, PF. Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. J Biol Chem 2007;282:21327–21336.CrossRefGoogle ScholarPubMed
Kohli, R, Feldstein, AE. NASH animal models: Are we there yet? J Hepatol 2011;55:941–943.CrossRefGoogle ScholarPubMed
Sookoian, S, Pirola, CJ. Meta-analysis of the influence of I148M variant of patatin-like phosp holipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011;53:1883–1894.CrossRefGoogle Scholar
Santoro, N, Kursawe, R, D’Adamo, E, 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;52:1281–1290.CrossRefGoogle ScholarPubMed
Valenti, L, Alisi, A, Galmozzi, E, et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology 2010;52:1274–1280.CrossRefGoogle ScholarPubMed
Petersen, KF, Dufour, S, Hariri, A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362:1082–1089.CrossRefGoogle ScholarPubMed
Al-Serri, A, Anstee, QM, Valenti, L, et al. The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies. J Hepatol 2012;56:448–454.CrossRefGoogle ScholarPubMed
Lin, YC, Chang, PF, Hu, FC, Chang, MH, Ni, YH. Variants in the UGT1A1 gene and the risk of pediatric nonalcoholic fatty liver disease. Pediatrics 2009;124:e1221–e1227.CrossRefGoogle ScholarPubMed
Abdelmalek, MF, Suzuki, A, Guy, C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 2010;51:1961–1971.CrossRefGoogle ScholarPubMed
Welsh, JA, Sharma, A, Abramson, JL, et al. Caloric sweetener consumption and dyslipidemia among US adults. JAMA 2010;303:1490–1497.CrossRefGoogle ScholarPubMed
Barlow, SE. Expert Committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007;120(Suppl 1):S164–S192.CrossRefGoogle ScholarPubMed
Lee, TH, Kim, WR, Benson, JT, Therneau, TM, Melton, LJ. Serum aminotransferase activity and mortality risk in a United States community. Hepatology 2008;47:880–887.CrossRefGoogle Scholar
Maffeis, C, Banzato, C, Talamini, G. Waist-to-height ratio, a useful index to identify high metabolic risk in overweight children. J Pediatr 2008;152:207–213.CrossRefGoogle ScholarPubMed
Nobili, V, Alisi, A, Vania, A, 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.CrossRefGoogle ScholarPubMed
Loomba, R, Wesley, R, Pucino, F, et al. Placebo in nonalcoholic steatohepatitis: insight into natural history and implications for future clinical trials. Clin Gastroenterol Hepatol 2008;6:1243–1248.CrossRefGoogle ScholarPubMed
Patton, HM, Lavine, JE, van Natta, ML, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135:1961–1971.CrossRefGoogle ScholarPubMed
Carter-Kent, C, Yerian, LM, Brunt, EM, et al. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009;50:1113–1120.CrossRefGoogle ScholarPubMed
Wieckowska, A, Zein, NN, Yerian, LM, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44:27–33.CrossRefGoogle ScholarPubMed
Alkhouri, N, Carter-Kent, C, Lopez, R, et al. A combination of the pediatric NAFLD fibrosis index and enhanced liver fibrosis test identifies children with fibrosis. Clin Gastroenterol Hepatol 2011;9:150–155.CrossRefGoogle ScholarPubMed
Nobili, V, Vizzutti, F, Arena, U, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008;48:442–448.CrossRefGoogle Scholar
Larson, SP, Bowers, SP, Palekar, NA, 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;5:1329–1332.CrossRefGoogle ScholarPubMed
West, J, Card, TR. Reduced mortality rates following elective percutaneous liver biopsies. Gastroenterology 2010;139:1230–1237.CrossRefGoogle ScholarPubMed
Potter, C, Hogan, MJ, Henry-Kendjorsky, K, Balint, J, Barnard, JA. Safety of pediatric percutaneous liver biopsy performed by interventional radiologists. J Pediatr Gastroenterol Nutr 2011;53:202–206.CrossRefGoogle ScholarPubMed
Brunt, EM, Kleiner, DE, Wilson, LA, Belt, P, Neuschwander-Tetri, BA. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 2011;53:810–820.CrossRefGoogle ScholarPubMed
Kleiner, DE, Brunt, EM, Van Natta, M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.CrossRefGoogle ScholarPubMed
Schwimmer, JB, Behling, C, Newbury, R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005;42:641–649.CrossRefGoogle ScholarPubMed
Musso, G, Gambino, R, Cassader, M, Pagano, G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52:79–104.CrossRefGoogle ScholarPubMed
Nobili, V, Marcellini, M, Devito, R, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 2006;44:458–465.CrossRefGoogle ScholarPubMed
DeVore, S, Kohli, R, Lake, K, et al. A multidisciplinary clinical program is effective in stabilizing BMI and reducing ALT in pediatric patients with NAFLD. J Pediatr Gastroenterol Nutr 2013;57:119–123.CrossRefGoogle Scholar
Nobili, V, Manco, M, Devito, R, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008;48:119–128.CrossRefGoogle ScholarPubMed
Lavine, JE, Schwimmer, JB, van Natta, ML, 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;305:1659–1668.CrossRefGoogle ScholarPubMed
Sanyal, AJ, Chalasani, N, Kowdley, KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675–1685.CrossRefGoogle ScholarPubMed
Klein, EA, Thompson, JR, Tangen, CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549–1556.CrossRefGoogle Scholar
Dohil, R, Schmeltzer, S, Cabrera, BL, et al. Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011;33:1036–1044.CrossRefGoogle ScholarPubMed
Chavez-Tapia, NC, Tellez-Avila, FI, Barrientos-Gutierrez, T, et al. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010;(1):CD007340.Google Scholar
Xanthakos, SA, Miles, L, Bove, K, Inge, T. Outcome of nonalcoholic fatty liver disease (NAFLD) in adolescents after bariatric surgery. Obesity (Silver Spring), 2007;15(Suppl 1):A209.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] 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.

  • Non-alcoholic fatty liver disease in children
    • By Rohit Kohli, Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati Children’s Steatohepatitis Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Kevin E. Bove, Division of Pediatric Pathology, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Stavra A. Xanthakos, Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.037
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.

  • Non-alcoholic fatty liver disease in children
    • By Rohit Kohli, Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati Children’s Steatohepatitis Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Kevin E. Bove, Division of Pediatric Pathology, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Stavra A. Xanthakos, Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.037
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.

  • Non-alcoholic fatty liver disease in children
    • By Rohit Kohli, Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati Children’s Steatohepatitis Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Kevin E. Bove, Division of Pediatric Pathology, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Stavra A. Xanthakos, Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  • Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
  • Book: Liver Disease in Children
  • Online publication: 05 March 2014
  • Chapter DOI: https://doi.org/10.1017/CBO9781139012102.037
Available formats
×