Nonalcoholic Fatty Liver Disease In Children

Introduction                  

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

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5. 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.
6. 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.
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8. 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.
9. 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.
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13 .Valerio Nobili Bambino Gesù” Children Hospital, P.zzle Sant’Onofrio, 4, 00165 Rome iTALY