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Special Report

Unmet needs in pediatric NAFLD research: what do we need to prioritize for the future?

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Pages 961-967 | Received 06 May 2018, Accepted 14 Aug 2018, Published online: 21 Aug 2018

References

  • Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.
  • Schwimmer JB, Deutsch R, Kahen T, et al. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–1393.
  • Anderson EL, Howe LD, Jones HE, et al. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PloS One. 2015;10:e0140908.
  • Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–1048.
  • Day CP, James OFW. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–845.
  • Marchesini G, Brizi M, Morselli-Labate AM, et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J of Med. 1999;107:450–455.
  • Orlik B, Handzlik G, Olszanecka-Glinianowicz M. The role of adipokines and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease. Postepy Hig I Med Dosw. 2010;64:212–219.
  • White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10:1342–1359.
  • Stepanova M, Rafig N, Makhlouf H, et al. Predictors of all-cause mortality and liver-related mortality in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Dig Dis Sci. 2013;58:3017–3023.
  • Zafrani ES. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Arch. 2004;444:3–12.
  • Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis. 2004;24:3–20.
  • Nobili V, Alisi A, Newton KP, et al. Comparison of the phenotype and approach to pediatric vs adult patients with nonalcoholic fatty liver disease. Gastroenterology. 2016;150:1798–1810.
  • Hubscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathology. 2006;49:450–465.
  • Adolph TE, Grander C, Grabherr F, et al. Adipokines and non-alcoholic fatty liver disease: multiple interactions. Int J Mol Sci. 2017;18:pii: E1649.
  • Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2017;66:180–190.
  • Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014;146:1513–1524.
  • Zhu LX, Baker RD, Baker SS. Gut microbiome and nonalcoholic fatty liver diseases. Pediatr Res. 2015;77:245–251.
  • Littman DR, Pamer EG. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe. 2011;10:311–323.
  • Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336:1268–1273.
  • Burcelin R, Serino M, Chabo C, et al. Metagenome and metabolism: the tissue microbiota hypothesis. Diabetes Obes Metab. 2013;15:61–70.
  • Backhed F. Programming of host metabolism by the gut microbiota. Ann Nutr Metab. 2011;58:44–52.
  • Caesar R, Fåk F, Bäckhed F. Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med. 2010;268:320–328.
  • Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313–323.
  • Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336:489–493.
  • Garcia-Larsen V, Ierodiakonou D, Jarroid K, et al. Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis. PloS Med. 2018;15:e1002507.
  • Schwartz S, Friedberg I, Ivanov IV, et al. A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol. 2012;13:r32.
  • Bokulich NA, Chung J, Battaglia T, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8:343ra82.
  • Madan JC, Hoen AG, Lundgren SN, et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr. 2016;170:212–219.
  • Chu DM, Antony KM, Ma J, et al. The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med. 2016;8:77.
  • Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–721.
  • Fernandez L, Langa S, Martin V, et al. The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res. 2013;69:1–10.
  • O’Sullivan A, Farver M, Smilowitz JT. The influence of early infant-feeding practices on the intestinal microbiome and body composition in infants. Nutr Met Insights. 2016;8:87.
  • Salminen S, Bouley C, Boutron-Ruault MC, et al. Functional food science and gastrointestinal physiology and function. Br J of Nutr. 1998;80:147–171.
  • Zhang HS, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106:2365–2370.
  • Ma J, Prince AL, Bader D, et al. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat Commun. 2014;5:3889.
  • Oben JA, Mouralidarane A, Samuelsson AM, et al. Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice. J Hepatology. 2010;52:913–920.
  • Wankhade UD, Zhong Y, Kang P, et al. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PloS One. 2017;12:e0175675.
  • Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–484.
  • Le Roy T, Llopis M, Lepage P, et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2013;62:1787–1794.
  • Nobili V, Bedogni G, Alisi A, et al. A protective effect of breastfeeding on the progression of non-alcoholic fatty liver disease. Arch Dis Child. 2009;94:801–805.
  • Vajro P, Paolella G, Fasano A. Microbiota and gut-liver axis: their influences on obesity and obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2013;56:461–468.
  • Ceccarelli S, Panera N, Mina M, et al. LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease. Oncotarget. 2015;6:41434–41452.
  • Alisi A, Manco M, Devito R, et al. Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2010;50:645–649.
  • Pouteau E, Nguyen P, Ballèvre O, et al. Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes. Proc Nutr Soc. 2003;62:87–93.
  • Zhu L, Baker SS, Gill C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57:601–609.
  • Cope K, Risby T, Diehl AM. Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology. 2000;119:1340–1347.
  • Engstler AJ, Aumiller T, Degen C, et al. Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease. Gut. 2016;65:1564–1571.
  • Del Chierico F, Nobili V, Vernocchi P, et al. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology. 2017;65:451–464.
  • Den Besten G, Bleeker A, Gerding A, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARG-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64:2398–2408.
  • Gill PA, van Zelm MC, Muir JG, et al. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018;48:15–34.
  • Leung C, Rivera L, Furness JB, et al. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13:412–425.
  • Michail S, Lin M, Frey MR, et al. Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS Microbiol Ecol. 2015;91:1–9.
  • Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101:15718–15723.
  • Bugianesi E, Bizzarri C, Rosso C, et al. Low birthweight increases the likelihood of severe steatosis in pediatric non-alcoholic fatty liver disease. Am J Gastroenterol. 2017;112:1277–1286.
  • Ley RE, Turnbaugh PJ, Klein S, et al. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–1023.
  • Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Int J Epidemiol. 2013;42:1215–1222.
  • Catalano PM, Presley L, Minium J, et al. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care. 2009;32:1076–1080.
  • Barker DJP. In utero programming of chronic disease. Clin Sci (Lond). 1998;95:115–128.
  • Ma YY, Li L, Yu CH, et al. Effects of probiotics on nonalcoholic fatty liver disease: A meta-analysis. World J Gastroenterol. 2013;19:6911–6918.
  • Eslamparast T, Poustchi H, Zamani F, et al. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr. 2014;99:535–542.
  • Fan JG, Xu ZJ, Wang GL. Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model. World J Gastroenterol. 2005;11:5053–5056.
  • Manzhalii E, Virchenko O, Falayeyeva T, et al. Treatment efficacy of a probiotic preparation for non-alcoholic steatohepatitis: a pilot trial. J Dig Dis. 2017;18:698–703.
  • Holscher HD, Faust KL, Czerkies LA, et al. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. JPEN J Parenter Enteral Nutr. 2012;36:95S–105S.
  • Endo H, Niioka M, Kobayashi N, et al. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis. PloS One. 2013;8:e63388.
  • Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509–1517.
  • Nier A, Enlster AJ, Maier IB, et al. Markers of intestinal permeability are already altered in early stages of non-alcoholic fatty liver disease: studies in children. PLoS One. 2017;12:e0183282.
  • Guercio Nuzio S, Di Stasi M, Pierri L, et al. Multiple gut–liver axis abnormalities in children with obesity with and without hepatic involvement. Pediatr Obes. 2017;12:446–452.
  • Rao S, Simmer K, Patole S. Probiotic supplementation in neonates with major gastrointestinal surgical conditions: a systematic review. J Matern Fetal Neonatal Med. 2018;31:1517–1523.
  • Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL# 3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39:1276–1285.
  • Vajro P, Mandato C, Licenziati MR, et al. Effects of lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52:740–743.
  • Famouri F, Shariat Z, Hashemipour M, et al. Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. J Pediatr Gastroenterol Nutr. 2017;64:413–417.
  • Panasevich MR, Peppler WT, Oerther DB, et al. Microbiome and NAFLD: potential influence of aerobic fitness and lifestyle modification. Physiol Genomics. 2017;49:385–399.
  • Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–916.
  • Fermin CR, Lee AM, Filipp SL, et al. Serum alanine aminotransferase trends and their relationship with obesity and metabolic syndrome in united states adolescents, 1999-2014. Metab Syndr Relat Disord. 2017;15:276–282.
  • Marzuillo P, Del Giudice EM, Santoro N. Pediatric fatty liver disease: role of ethnicity and genetics. World J Gastroenterol. 2014;20:7347–7355.
  • Hunt KJ, Resendez RG, Williams K, et al. National cholesterol education program versus world health organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio heart study. Circulation. 2004;110:1251–1257.
  • Boyraz M, Hatipoglu N, Sari E, et al. Non-alcoholic fatty liver disease in obese children and the relationship between metabolic syndrome criteria. Obes Res Clin Pract. 2014;8:E356–E363.
  • Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med. 2011;62:361–380.
  • Madan SA, John F, Pyrsopoulos N, et al. Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis. Eur J of Gastroenterol Hepatol. 2015;27:1237–1248.
  • Gibson PS, Lang S, Gilbert M, et al. Assessment of diet and physical activity in paediatric non-alcoholic fatty liver disease patients: a United Kingdom case control study. Nutrients. 2015;7:9721–9733.
  • Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67:1265–1273.
  • Angulo P, Bugianesi E, Bjornsson ES, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145:782–789.
  • Seki E, Brenner DA. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology. 2008;48:322–335.
  • Parker GA, Picut CA. Immune functioning in non lymphoid organs: the liver. Toxicol Pathol. 2012;40:237–247.
  • Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88:125–172.
  • Paik YH, Kim J, Aoyama T, et al. Role of NADPH oxidases in liver fibrosis. Antioxid Redox Signal. 2014;20:2854–2872.
  • Baffy G. Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J Hepatol. 2009;51:212–223.
  • Ma X, Hua J, Mohamood AR, et al. A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury. Hepatology. 2007;46:1519–1529.
  • Henning JR, Graffeo GS, Rehman A, et al. Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice. Hepatology. 2013;58:589–602.
  • Krenkel O, Puengel T, Govaere O, et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology. 2018;67:1270–1283.

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