Pediatric Metabolic (dysfunction)-associated Fatty Liver Disease: Current Insights and Future Perspectives

Overview

Journal Hepatol Int

Publisher Springer

Specialty Gastroenterology

Date 2024 Jun 16

PMID 38879851

Authors

Sunitha Vimalesvaran

Pietro Vajro

Anil Dhawan

Affiliations

Soon will be listed here.

Abstract

The historical use of the term non-alcoholic fatty liver disease (NAFLD) in obese/overweight children has been controversial as to the appropriateness of this terminology in children, and lately, in adults too. Newer game-changer terminology, metabolic (dysfunction)-associated fatty liver disease (MAFLD), for this condition signifies a positive step forward that addresses the limitations of the previous definition for both adults and children. The prevalence of MAFLD has surged in tandem with the global rise in obesity rates, establishing itself as a predominant cause of chronic liver disease in both adult and pediatric populations. The adoption of the recently proposed nomenclature reflects a more encompassing comprehension of the disease and its etiology compared to its predecessor, NAFLD. Notably, the revised terminology facilitates the recognition of MAFLD as an autonomous condition while acknowledging the potential coexistence of other systemic fatty liver disorders. Particularly in children, this includes various paediatric-onset genetic and inherited metabolic disorders, necessitating thorough exclusion, especially in cases where weight loss interventions yield no improvement or in the absence of obesity. MAFLD presents as a multifaceted disorder; evidence suggests its origins lie in a complex interplay of nutritional, genetic, hormonal, and environmental factors. Despite advancements, current non-invasive diagnostic biomarkers exhibit limitations in accuracy, often necessitating imaging and histological evaluations for definitive diagnosis. While dietary and lifestyle modifications stand as cornerstone measures for MAFLD prevention and management, ongoing evaluation of therapeutic agents continues. This article provides an overview of the latest developments and emerging therapies in the realm of paediatric MAFLD.

References

Till H, Mann O, Singer G, Weihrauch-Bluher S . Update on Metabolic Bariatric Surgery for Morbidly Obese Adolescents. Children (Basel). 2021; 8(5). PMC: 8151410. DOI: 10.3390/children8050372. View

Chan D, Nelson E, Li A, Woo J, Sea M, Chan R . Lifestyle intervention in obese Chinese adolescents with non-alcoholic fatty liver disease: a randomised controlled study. Hong Kong Med J. 2018; 24 Suppl 4(4):12-15. View

Alberti G, Gana J, Santos J . Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease. Nutrients. 2020; 12(11). PMC: 7698421. DOI: 10.3390/nu12113531. View

Mandala A, Janssen R, Palle S, Short K, Friedman J . Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients. 2020; 12(10). PMC: 7602751. DOI: 10.3390/nu12103166. View

Gronbaek H, Lange A, Birkebaek N, Holland-Fischer P, Solvig J, Horlyck A . Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese Danish children. J Pediatr Gastroenterol Nutr. 2011; 54(2):223-8. DOI: 10.1097/MPG.0b013e31822cdedf. View

Zou Z, Zeng J, Ren T, Huang L, Wang M, Shi Y . The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta-analysis. Liver Int. 2021; 42(9):1969-1980. DOI: 10.1111/liv.15080. View

Dionysopoulos G, Kalopitas G, Vadarlis A, Bakaloudi D, Gkiourtzis N, Karanika E . Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022; 63(27):8545-8553. DOI: 10.1080/10408398.2022.2062589. View

Vajro P, Franzese A, Valerio G, Iannucci M, Aragione N . Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children. J Pediatr. 2000; 136(6):739-43. View

Rupasinghe K, Hind J, Hegarty R . Updates in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Children. J Pediatr Gastroenterol Nutr. 2023; 77(5):583-591. DOI: 10.1097/MPG.0000000000003919. View

10.

Michail S, Lin M, Frey M, Fanter R, Paliy O, Hilbush B . Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS Microbiol Ecol. 2015; 91(2):1-9. PMC: 4358749. DOI: 10.1093/femsec/fiu002. View

11.

Alfani R, Vassallo E, De Anseris A, Nazzaro L, DAcunzo I, Porfito C . Pediatric Fatty Liver and Obesity: Not Always Justa Matter of Non-Alcoholic Fatty Liver Disease. Children (Basel). 2018; 5(12). PMC: 6306738. DOI: 10.3390/children5120169. View

12.

Lin X, Mai M, He T, Huang H, Zhang P, Xia E . Efficiency of ursodeoxycholic acid for the treatment of nonalcoholic steatohepatitis: A systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2022; 16(6):537-545. DOI: 10.1080/17474124.2022.2083605. View

13.

Welsh J, Karpen S, Vos M . Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr. 2012; 162(3):496-500.e1. PMC: 3649872. DOI: 10.1016/j.jpeds.2012.08.043. View

14.

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

15.

Abeysekera K, Fernandes G, Hammerton G, Portal A, Gordon F, Heron J . Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study. Lancet Gastroenterol Hepatol. 2020; 5(3):295-305. PMC: 7026693. DOI: 10.1016/S2468-1253(19)30419-4. View

16.

Gibson P, Lang S, Gilbert M, Kamat D, Bansal S, Ford-Adams M . Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study. Nutrients. 2015; 7(12):9721-33. PMC: 4690046. DOI: 10.3390/nu7125494. View

17.

Backhed F, Manchester J, Semenkovich C, Gordon J . Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007; 104(3):979-84. PMC: 1764762. DOI: 10.1073/pnas.0605374104. View

18.

Troisi J, Belmonte F, Bisogno A, Pierri L, Colucci A, Scala G . Metabolomic Salivary Signature of Pediatric Obesity Related Liver Disease and Metabolic Syndrome. Nutrients. 2019; 11(2). PMC: 6412994. DOI: 10.3390/nu11020274. View

19.

Farias C, Cisternas C, Gana J, Alberti G, Echeverria F, Videla L . Dietary and Nutritional Interventions in Nonalcoholic Fatty Liver Disease in Pediatrics. Nutrients. 2023; 15(22). PMC: 10674812. DOI: 10.3390/nu15224829. View

20.

Eslam M, Alkhouri N, Vajro P, Baumann U, Weiss R, Socha P . Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement. Lancet Gastroenterol Hepatol. 2021; 6(10):864-873. DOI: 10.1016/S2468-1253(21)00183-7. View