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Unmet needs in pediatric NAFLD research: what do we need to prioritize for the future?
Grace Hatton1, Tommaso Alterio2, Valerio Nobili2,3
1a Department of Medicine , King's College Hospital , London , UK.
Insights
Pediatric nonalcoholic fatty liver disease (NAFLD) requires further research into its causes and progression. Understanding the gut microbiome, risk factors, and inflammation is key to developing effective treatments for children.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Microbiome Research
Background:
- Pediatric nonalcoholic fatty liver disease (NAFLD) is a prevalent condition with complex mechanisms and unclear long-term impacts.
- Despite advancements, significant knowledge gaps persist regarding its pathophysiology and clinical significance in children.
Purpose of the Study:
- To identify and discuss unmet needs in pediatric NAFLD and nonalcoholic steatohepatitis (NASH) research.
- To highlight areas requiring further investigation, including the gut microbiome, perinatal influences, risk stratification, and portal inflammation.
Main Methods:
- Systematic literature search of PubMed/MEDLINE and Embase databases.
- Focus on articles published between January 1998 and January 2018.
- Identification of 'unmet needs' based on expert commentary and current research gaps.
Main Results:
- The relationship between the gut microbiome, perinatal factors, and NAFLD development needs clarification.
- Effective methods for risk stratification of pediatric NAFLD patients for cardiovascular, diabetic, and hepatic diseases are lacking.
- Mechanisms of portal inflammation in pediatric NASH, potentially differing from adults, remain poorly understood.
Conclusions:
- Further research into the interplay of the gut microbiome and perinatal factors is crucial for understanding and potentially preventing pediatric NAFLD and metabolic syndrome.
- Developing accurate risk stratification tools is essential for targeted interventions in children with NAFLD.
- Elucidating the immune processes in pediatric NASH may reveal novel therapeutic targets.
Introduction:
Pediatric nonalcoholic fatty liver disease (NAFLD) is common disorder that has complex pathophysiology and unquantified clinical significance. Though there have been major advances in the field, there is much yet to be understood. Areas covered: PubMed/MEDLINE and Embase were searched for articles related to pediatric NAFLD and nonalcoholic steatohepatitis (NASH) between January 1998 and January 2018. The areas considered to be 'unmet needs' were the relationship between the intestinal microbiome and perinatal events, clinical event risk stratification, and mechanisms underlying portal inflammation. Expert commentary: In utero and ex utero factors have been associated with NAFLD and also with the intestinal microbiome, but it is not yet known how intestinal dysbiosis can be reversed and whether intervention in high-risk neonates could alter their propensity for the metabolic syndrome. Children with NAFLD are at increased risk of cardiovascular, diabetic, and hepatic diseases, but it is unclear how best to stratify children into appropriate risk groups for targeted interventions. Finally, the immune processes underlying pediatric NASH are thought to differ to those in adult NASH, yet the events surrounding activation of periportal lymphocytes are poorly understood. Deepening our understanding of these topics may lead to novel therapeutic targets.
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