Measuring Fatty Liver With Ultrasound and MRS in Children With Overweight or Obesity

Study Overview
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Brief Summary
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Obesity is associated with a variety of comorbidities, amongst which non-alcoholic fatty liver disease (NAFLD). A recent meta-analysis has shown that the prevalence of NAFLD in obese pediatric populations is around 35%, compared to approximately 8% in general pediatric populations, making it a very important health threat in these populations. The golden standard for diagnosis of NAFLD is liver biopsy. However, since liver biopsy is associated with a certain risk of morbidity and mortality, this method is inappropriate for screening large populations at-risk for developing NAFLD. Magnetic resonance spectroscopy has demonstrated excellent correlation with liver biopsy and the is the most accuratete non-invasive method to measure liver fat content in children. However, MRS is expensive and not available in all centres. A novel ultrasonographic measurement to quantitatively assess liver steatosis is the hepatorenal index (HRI). Previous studies have shown high sensitivity and specificity of the HRI, as compared to MRS and liver biopsy. However, this measurement has never been validated in children. In this study, the HRI will be compared to MRS in children with obesity, to validate the HRI and to determine cut-off points.

Detailed Description
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Rationale: Obesity is associated with a variety of co-morbidities. Children with obesity are more likely to have risk factors associated with cardiovascular disease (eg, hypertension, high cholesterol, and type 2 diabetes mellitus), but also non-alcoholic fatty liver disease (NAFLD). A recent meta-analysis has shown that the prevalence of NAFLD in obese pediatric populations is approximately 35%, compared to approximately 8% in general pediatric populations [6], making it a very important health threat in these populations. The golden standard for the diagnosis of NAFLD is liver biopsy. However, since liver biopsy is associated with a certain risk of morbidity and mortality, this method is inappropriate for screening large populations at-risk for developing NAFLD. Magnetic resonance spectroscopy has demonstrated excellent correlation with liver biopsy and the most accurate non-invasive method to measure liver fat content in children. However, MRS is an expensive method that is not available in all centers. A novel ultrasonographic measurement to quantitatively assess liver steatosis is the hepatorenal index (HRI), which is calculated as the ratio of hepatic and renal ultrasonographic brightness. Previous studies in adults have shown a high sensitivity and specificity of the HRI, as compared to liver biopsy as well as H-MRS. However, the measurement of the HRI has never been validated in children. The validation of this simple, non-invasive method to quantitatively assess fat accumulation in the liver, could improve the screening for, and follow-up of, NAFLD in at-risk populations. Objective: The aim of this study is to validate the ultrasonographic hepatorenal index in children with overweight, obesity and morbid obesity, by using MRS, and to determine cut-off points for the HRI according to liver fat percentages measured with MRS. Study design: cross-sectional study Study population: Overweight and obese children from the Centre for Overweight Adolescent and Childrens Healthcare (COACH) program. Main study parameters/endpoints: Ultrasonographic hepato-renal index and liver fat percentage as determined by magnetic resonance spectroscopy. Secondary study parameters/endpoints: correlate liver fat percentage as measured with MRS, and HRI, with anthropometric, metabolic and cardiovascular parameters.

Official Title
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Measuring Fatty Liver With Ultrasound and MRS in Children With Overweight or Obesity (Dutch Title: Het Meten Van Leververvetting Met Echo en MRS in Kinderen Met Overgewicht of Obesitas)

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Magnetic resonance spectroscopy measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in the COACH program Aged below 18 years Exclusion Criteria: · Implanted medical devices such as pacemakers or neurostimulators Metal objects in the body (for instances prosthetics, piercings, metal parts in the eye, permanent eyeliner) Previous brain surgery Cardiac arrhythmia Epilepsy Claustrofobia Not wanting to be informed about accidental findings on MRS

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with suspected NAFLD<br>Children with overweight or obesity. Both children that are and children that are not suspected of having NAFLD (based on ultrasound and laboratory findings) are included. | Other: Magnetic resonance spectroscopy measurement<br>* Magnetic resonance spectroscopy measurement will be performed to measure liver fat content.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ultrasonographic hepato-renal index | Ratio of hepatic and renal echogenicity | Until december 2019 | 
| Liver fat percentage | Liver fat percentage will be measured withmagnetic resonance spectroscopy. | Until december 2019 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI z-score | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 
| Liver enzyme levels | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 
| Fibrosan values | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 
| Lipid spectrum | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 
| Glucose metabolism | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 
| Blood pressure | Secondary outcomes will be correlated with liver fat percentage as measured with MRS and with the ultrasonographic hepato-renal index | Until december 2019 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Alcoholic Fatty Liver Disease, Magnetic Resonance Spectroscopy, Ultrasonographic hepatorenal index