Abstract
Purpose of Review
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in both adults and children. In this article, we review recent developments in the screening, diagnosis, and treatment of pediatric NAFLD.
Recent Findings
Although alanine aminotransferase (ALT) remains the best screening test for NAFLD in children, and liver biopsy is still required for the diagnosis of nonalcoholic steatohepatitis (NASH), other noninvasive biomarker/imaging studies (MRI-PDFF and VCTE) have emerged as diagnostic methods for pediatric NAFLD. Two large clinical therapeutic trials testing vitamin E, metformin, and cysteamine in pediatric NAFLD yielded mostly inconclusive results. Bariatric surgery has begun to be used in adolescents with severe obesity. An adult phase 2 study using obeticholic acid (OCA) to treat NASH patients with fibrosis showed some positive results. As we continue to await the first FDA-approved therapeutic agent for NASH, lifestyle change remains the main modality of treatment.
Summary
Newer diagnostic and treatment modalities for pediatric NAFLD continue to be in development under FDA guidance.
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References
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Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.
Anstee QM, McPherson S, Day CP. How big a problem is non-alcoholic fatty liver disease? BMJ. 2011;343:d3897.
Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686–90.
Yu EL, Golshan S, Harlow KE, Angeles JE, Durelle J, Goyal NP, et al. Prevalence of nonalcoholic fatty liver disease in children with obesity. J Pediatr. 2019;207:64–70.
Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: prevalence and impact on world health. Hepatology. 2016;64(1):19–22.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.
Welsh JA, Karpen S, Von MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010. J Pediatr. 2013;162(3):496–500.e1.
Riley MR, Bass NM, Rosenthal P, Merriman RB. Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists. J Pediatr. 2005;147(6):839–42.
Barlow SE. Expert Committee. 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.
Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, 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.
Schwimmer JB, Newton KP, Awai HI, Choi LJ, Garcia MA, Ellis LL, et al. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38(10):1267–77.
Awai HI, Newton KP, Sirlin CB, Behling C, Schwimmer JB. Evidence and recommendations for imaging liver fat in children, based on systemic review. Clin Gastroenterol Hepatol. 2014;12(5):765–73.
Schwimmer JB, Middleton MS, Behling C, Newton KP, Awai HI, Paiz MN, et al. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology. 2015;61(6):1887–95.
Bohte AE, van Werven JR, Bipat S, Stoker J. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol. 2011;21(1):87–97.
Loomba R, Sirlin CB, Schwimmer JB, Lavine J. Advances in pediatric nonalcoholic fatty liver disease. Hepatology. 2009;50(4):1282–93.
Vuppalanchi R, Gould RJ, Wilson LA, Unalp-Arida A, Cummings OW, Chalasani N, et al. Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int. 2012;6(1):379–85.
Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork N, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology. 2009;136(5):1585–92.
Loomba R, Chalasani N. The hierarchical model of NAFLD: prognostic significance of histologic features in NASH. Gastroenterology. 2015;149(2):278–81.
Tang A, Desai A, Hamilton G, Wolfson T, Gamst A, Lam J, et al. Accuracy of MR imaging-estimated proton density fat fraction for classification of dichotomized histologic grades and nonalcoholic fatty liver disease. Radiology. 2015;274(2):416–25.
Middleton MS, Van Natta ML, Heba ER, Alazraki A, Trout AT. Masand P Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease. Hepatology. 2018;67(3):858–72.
Nobili V, Vizzutti F, Arena U, Abraldes JG, Marra F, Peitrobattista A, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology. 2008;48(2):442–8.
Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014;164(1):186–8.
Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology. 2008;48(1):119–28.
•• Schwimmer JB, Ugalde-Nicalo P, Welsh JA, Angeles JE, Cordero M, Harlow, 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. This study showed the provision of a diet low in free sugar result in significant improvement of hepatic steatosis in adolescents with NAFLD.
Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, 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.
Dohil R, Cabrera BL SS, Wang T, Durelle J, Duke KB, et al. Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011;33(9):1036–44.
Schwimmer JB, Lavine JE, Wilson LA, Neuschwander-Tetri BA, Xanthakos SA, Kohli R, et al. In children with nonalcoholic fatty liver disease, cysteamine bitatrate delayed release improves liver enzymes but does not reduced disease activity scores. Gastroenterology. 2016;151(6):1141–54.
Lin CH, Kohli R. Bile acid metabolism and signaling: potential therapeutic target for nonalcoholic fatty liver disease. Clin Transl Gastroenterol. 2018;9(6):164.
Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145(3):574–82.
•• Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman A, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicenter, randomized, placebo-controlled phase 3 trial. Lancet. 2019;394(10215):2184–96. The study showed obeticholic acid significantly improved fibrosis and key component of NASH disease activity among adult patients with NASH.
Eslam M, Alvani R, Shiha G. Obeticholic acid: towards first approval for NASH. Lancet. 2019;394(10215):2131–3.
Inge TH, Courcoulas AP, Jenkins TM, Michalsky MP, Helmrath MA, Brandt ML, et al. Weight loss and health status 3 years after bariatric surgery in adolescents. N Engl J Med. 2016;374(2):113–23.
Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379–88.
Manco M, Mosca A, De Peppo F, Caccamo R, Gutrera R, Cutrera R, et al. The benefit of sleeve gastrectomy in obese adolescents on nonalcoholic steatohepatitis and hepatic fibrosis. J Pediatr. 2017;180:31–7.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367–78.
US Department of Health and Human Services. Noncirrhotic nonalcoholic steatohepatitis with liver fibrosis: developing drugs for treatment. Guidance for industry. December 2018. https://www.fda.gov/media/119044/download (accessed June 30, 2020).
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RK served as a consultant for Intercept Pharmaceuticals. CHL: none.
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Lin, CH., Kohli, R. Emerging New Diagnostic Modalities and Therapies of Nonalcoholic Fatty Liver Disease. Curr Gastroenterol Rep 22, 52 (2020). https://doi.org/10.1007/s11894-020-00786-y
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DOI: https://doi.org/10.1007/s11894-020-00786-y