Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence in concert with the global epidemic of obesity and is being diagnosed at increasingly younger ages. NAFLD includes a broad spectrum of liver conditions, ranging from fat accumulation in hepatocytes (nonalcoholic fatty liver) to nonalcoholic steatohepatitis (NASH), which is characterized by tissue necro-inflammation, hepatocyte injury (hepatocellular ballooning) and fibrosis at different stages (steatofibrosis). Current evidence suggest that NASH can progress to cirrhosis and end-stage liver disease requiring liver transplantation. At present, liver biopsy represents the reference standard for the diagnosis of NAFLD and for grading and staging disease severity. However, the invasiveness of the procedure is the primary limitation for its use to screen large numbers of subjects at risk, or be performed repeatedly to measure fat changes following treatment. Therefore, because of the high prevalence of NAFLD and its progressive nature, there has been an urgent need to develop and validate reliable noninvasive tests that can accurately predict the presence of advanced disease and allow for disease monitoring without the need for liver biopsy. Also, it is reasonable to assume that early detection of the disease and its complications may strongly influence the choice of treatment, leading to better long-term outcomes. The purpose of this research is to prospectively assess the diagnostic performance of new biomarkers and imaging techniques such as multiparametric ultrasound for the diagnosis of NAFLD, NASH and fibrosis.
Establishing the diagnosis of NAFLD and disease severity as well as monitoring the disease over time remain major challenges for pediatricians caring for the growing number of youths with NAFLD. The early diagnosis of NAFLD is an important issue at all ages but especially in at-risk children who are obese because of the tendency of the disease to progress in both adolescents and young adults. Also, it is reasonable to assume that early detection of the disease may strongly influence the choice of treatment, leading to better long-term outcomes.
Therefore, identifying and validating potential novel non-invasive biomarkers and imaging techniques is a critical area of research in paediatric NAFLD. Diagnostics development in the area of NAFLD research can be divided into two major groups: modalities to detect and quantify the presence of fibrosis and modalities directed at establishing the diagnosis of NASH.
To this end, a large population of overweight/obese youth will undergo a comprehensive and complete analysis of novel biomarkers and imaging techniques in comparison with age- and gender-matched normal weight subjects, an approach that has not been used so far.
Expected results
1) Validation of biomarkers such as cytokeratin-18, tissue inhibitor of metalloproteinases 1, amino-terminal propeptide of type III procollagen and hyaluronic acid for the diagnosis of NASH and fibrosis;
2) Validation of multiparametric ultrasound for the diagnosis as well as monitoring of NAFLD and its complications.
Early identification of children and adolescents with MHO provides an excellent opportunity for primary prevention at the population level, by instituting simple lifestyle changes, such as weight loss and regular physical exercise, that can prevent severe hepatic complications.