Nonalcoholic Fatty Liver Disease In Children
Introduction. 어린이의 비알코올성 지방간 질환
Nonalcoholic fatty liver disease (NAFLD) is nowadays one of the leading causes of chronic liver disease in children
(1).
It is defined by hepatic fat infiltration >5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake (<20 g/day), evidence of viral, autoimmune or drug-induced liver disease.
It includes a spectrum of liver disease ranging from simple intra-hepatic fat accumulation (steatosis) to different degrees of necrotic inflammation and fibrosis (steatohepatitis [NASH])
(2). NAFLD growing incidence reflects the worldwide annual increase in the number of obese individuals. In fact, it is typically associated with metabolic dysfunctions, which determinates an increased risk of developing type 2 diabetes mellitus, metabolic syndrome (MS) and cardiovascular diseases, even in children.
The scientific literature does not give at the moment long-term follow-up data on the natural history and prognosis of pediatric NAFLD, but it is known that, in susceptible individuals, it can evolve to cirrhosis and hepatocellular carcinoma
Epidemiology and pathophysiology
Pediatric NAFLD prevalence is estimated to be between 3% and 10%.
Diagnosis
A recent position paper by the ESPGHAN Hepatology Committee (16) has clarified the diagnostic approach to NAFLD in childhood. NAFLD is more frequent in children aged more than 10 years and is usually present with overweight/obesity. The diagnosis of NAFLD needs the recognition of fatty liver, and the exclusion of other causes of steatosis (Table 1).
Liver biopsy is the current gold standard for the diagnosis of NAFLD, and it is the only way to distinguish between NASH and simple steatosis, and to determine fibrosis and the severity of liver damage.
Histological pattern
Histological assessments play an important role in the diagnosis and management of NAFLD in children. Thus it is important to carefully evaluate and discriminate among the different histological features which characterize NAFLD/NASH.
Steatosis
Hepatocellular steatosis, the principal hallmark of NAFLD, is the accumulation of lipids within the cytoplasm in > 5% of hepatocytes.
Ballooning
Ballooning is a degenerative modification of hepatocytes, that lose their normal polygonal shape, becoming swollen and round
Inflammation
Inflammatory infiltrate, constituted by a mix of lymphocytes and histiocytes, is mainly localized in lobules or in portal tracts.
Fibrosis
The fibrosis represents the manifestation of an advanced form of liver damage.
Scoring system
Currently, two main scoring systems exist to evaluate histological activity in NAFLD and NASH, and are used both in children and adults
Treatment
Several studies have demonstrated that lifestyle modifications, based on a dietary restriction and the promotion of physical activity, lead to an improvement of NAFLD (30-32).
Diet and lifestyle changes
Weight loss improves hepatic and extra-hepatic insulin sensitivity by reducing the delivery of free fatty acids (FFA) and through better peripheral glucose utilization
Antioxidants
Oxidative stress is considered a major contributor to NAFLD pathogenesis and its progression to NASH. Antioxidants, such as vitamin E, are therefore potentially valuable as a NAFLD/NASH therapy, breaking the chain reaction of lipid peroxidation and restoring the endogenous antioxidant/oxidant balance.
Insulin sensitizing agents
Metformin has also been well studied in the field of pediatric NAFLD
Omega-3 long-chain polyunsaturated fatty acids
Dietary supplements such as long-chain omega-3 polyunsaturated fatty acids have been used in adults with NAFLD
Hepatoprotective agents
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that might theoretically antagonize the progression of NAFLD/NASH
Probiotics
Recently, a new treatment strategy using probiotics was proposed for the treatment of NAFLD.
References AN SOURCE
- 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.
- Esposito E, Iacono A, Bianco G, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009;139:905–911.
- Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–1481.
- Iacono A, Raso GM, Canani RB, Calignano A, Meli R. Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms. J Nutr Biochem. 2011;22:699–711.
- Lirussi F, Mastropasqua E, Orando S, et al. Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev 2007, 1. CD005165.
- Lee J, Hong SW, Rhee EJ, Lee WY. GLP-1 Receptor Agonist and Non- Alcoholic Fatty Liver Disease. Diabetes Metab J. 2012;36:262–267.
- pediatrics 2/2021, www.cham.org/gastro
- Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med. 2007;13:552–559.
- Pediatrics 2/2021
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