Pediatric non-alcoholic fatty liver disease: an increasing public health issue

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that encompasses a wide spectrum of liver abnormalities ranging from simple liver steatosis to steatohepatitis (non-alcoholic steatohepatitis), which may be associated with fibrosis and progress to cirrhosis and end-stage liver disease. NAFLD has recently become the most common cause of chronic liver disease in children and adolescents. NAFLD prevalence, alongside obesity, continues to increase among pediatric patients. Obesity is believed to represent a major risk factor for NAFLD, which is considered to be the liver presentation of the metabolic syndrome. Although the pathogenesis of NAFLD is not fully understood, the notion that multiple factors affect disease development and progression is widely accepted. Both genetic background and environmental factors contribute to NAFLD development. A more complete understanding of the pathogenesis may aid in developing non-invasive diagnostic tools and identifying new therapeutic targets. Liver biopsy currently remains the gold standard for NAFLD diagnosis and staging. Although lifestyle and diet modifications are key in NAFLD treatment, the development of new pharmacological therapies is crucial for patients who are unresponsive to first-line therapy.

Conclusion: Pediatric NAFLD is an increasing public health issue that remains underdiagnosed. A large-scale screening in the high-risk population, especially among the overweight pediatric patients, should be considered, including measurement of serum transaminases and liver ultrasound. It is crucial to treat this condition as soon as possible in order to avoid the progression to end-stage liver disease.

Fig. 1

Pathogenesis of NAFLD: the “multiple-hit” hypothesis. Genetics, epigenetics, environmental factors, insulin resistance, and obesity influence fat accumulation in the liver (steatosis). The fatty liver is then predisposed to secondary hits, including oxidative stress, mitochondrial dysfunction, pro-inflammatory cytokines imbalance, and stellate cells activation, which lead to necro-inflammation and fibrosis (NASH non-alcoholic steatohepatitis)

Fig. 2

Clinical algorithm for the management of pediatric NAFLD. In case of unexplained elevated ALT, of obesity, and/or of other comorbidities (insulin resistance, dyslipidemia, diabetes mellitus, hypertension), we recommend to perform a dosage of the liver transaminases. In case of normalization of the liver tests, the child has to be followed regularly by his pediatrician and a prevention should be introduced (diet and exercise). If the ALT remain elevated, an ultrasonography (and if necessary, a transient elastography) is recommended in order to detect the presence of steatosis. Other causes of liver diseases should also be excluded. If NAFLD is suspected or if the etiology of the liver disease remains unclear, a liver biopsy is recommended in order to detect the presence of inflammation and/or fibrosis, to stage the disease, and to confirm the diagnosis. If the diagnosis of NAFLD is confirmed, lifestyle changes represent the first-line treatment. Pharmacological treatments can be considered for patients who do not adhere to or are unresponsive to lifestyle modifications