Review article: the management of paediatric nonalcoholic fatty liver disease

Abstract

Summary Background Paediatric nonalcoholic fatty liver disease (NAFLD) is a major public health concern given the recent increase in its prevalence and link to obesity and other metabolic comorbidities. Current treatment strategies involve lifestyle changes. Other surgical and pharmacologic interventions have been proposed; however, limited randomised controlled trials (RCTs) in the paediatric population restrict their use. Aim To review the current management of paediatric NAFLD, including lifestyle and pharmacologic interventions, and to formulate recommendations for study design for future studies. Methods A MEDLINE, Pubmed and Cochrane Review database search used a combination of keywords, including NAFLD, nonalcoholic steatohepatitis (NASH), paediatric, treatments, lifestyle changes, bariatric surgery, orlistat, metformin, thiazolidinediones, vitamin E, cysteamine bitartrate, ursodeoxycholic acid (UDCA), probiotics, omega‐3 fatty acids, pentoxyfylline, farnesoid X receptor agonist and toll‐like receptor modifiers. The articles were selected based on their relevance to the review. Results Lifestyle interventions involving diet and exercise remain first‐line treatment for paediatric NAFLD. Bariatric surgery, orlistat, insulin sensitisers and UDCA have been evaluated but are not recommended as first or second‐line therapy. Medications such as cysteamine bitartrate, probiotics, polyunsaturated fats and pentoxyfilline share beneficial effects in trials, however, there is a paucity of adequately powered RCTs in which liver histology is evaluated. Vitamin E has been shown to be effective and safe in improving NASH histology in children. Conclusions Lifestyle intervention should be first‐line treatment for paediatric NAFLD. Vitamin E should be considered for those with biopsy‐proven NASH or borderline NASH failing first‐line therapy. Other therapeutics show promising results but require larger RCTs with convincing endpoints. Improved screening techniques, objective validated inclusion criteria and outcome measures as well as rigour in study design are necessary for propelling therapeutic discovery.

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

“…Although several drug-based therapies, such as vitamin E and metformin, and dietary supplementation, including probiotics and docosahexaenoic acid, have shown beneficial effects on ballooning, steatosis and inflammation, fibrotic lesions are refractory to treatment [140] and the long-term outcome of paediatric NASH remains poor [141] .…”

The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline

“…In NAFLD not associated with lipodystrophy, diet and exercise are first-line treatments (72), and among pharmacological treatments, vitamin E (in children and adults) (73, 74) and pioglitazone (in adults) (73, 75) have shown the most consistent benefit for liver histopathology. However, these treatments have not been studied in patients with lipodystrophy and are not approved for NAFLD.…”

Effectiveness of a carbohydrate restricted diet to treat non-alcoholic fatty liver disease in adolescents with obesity: Trial design and methodology

“…The standard of care in the dietary management of children with NAFLD is a diet low in fat comprised of foods with low energy density, which served as the basis for the control diet group (31–32). The FRD was based on the USDA MyPlate Daily Food Plan for teenagers and consisted of 55:25:20% energy from carbohydrates: protein: fat (33).…”