New study to examine thre role of vitamin D in the progression of paediatric NAFLD

Children's Liver Disease FoundationChildren's Liver Disease Foundation (CLDF), the UK’s leading charity fighting childhood liver disease, is to fund a PhD student fellowship at the University of Surrey which will look at the role of vitamin D in the progression of paediatric non-alcoholic fatty liver disease (NAFLD), now recognised as the most common cause of childhood liver disease in the UK.

The £74,500 award will fund a three year study, to be led by Dr Bernadette Moore, a lecturer in molecular nutrition at the University, who will be working in collaboration with Kings College Hospital Paediatric Liver Clinic.

"We are thrilled that CLDF have agreed to fund this project which will enable us to find out more about a disease which is affecting increasing numbers of UK children," commented Dr Moore. "The incidence of paediatric NAFLD has risen sharply in past three decades, affecting an estimated 3–9% of all children and up to 70% of obese children."

"Whilst we know that people in the UK have low level vitamin D status during the winter due to the lack of sunlight, children with fatty liver disease have been shown to have particularly low levels and this deficiency is associated with more severe liver disease. This project will examine the diet and specific genes that can affect vitamin D levels in UK children with liver disease."

Over the next three years 60 children with a histological diagnosis of NAFLD attending the paediatric liver unit at Kings College Hospital will be prospectively recruited for genotyping, dietary assessment and measurement of serum25-hyroxyvitamin D and 1,25 hydroxyvitamin D . Patients will be genotyped for polymorphisms recently shown to affect vitamin D status in healthy populations and these gene variants will also be examined in archived samples from over 100 children with NAFLD and cohorts of other chronic paediatric liver diseases. In parallel, human hepatocytes and hepatic stellate cells will be stimulated in vitro to identify microRNAs regulated by vitamin D.

University of Surrey Research TeamIn the context of chronic liver disease, the prevalence of low serum 25-hdroxyyvitamin D (25(OH)D) has been reported to be as high as 90% and low serum concentrations of 25 (OH)D have been shown to correlate to the severity of NAFLD in adults and children. Furthermore recent experimental data from animal studies suggests both that vitamin D deficiency is involved in NAFLD progression and that vitamin D supplementation may have therapeutic benefit. However, whilst several lines of evidence suggest a role for vitamin D insufficiency in the development and progression of NAFLD, the molecular mechanisms by which vitamin D may have a protective effect on NAFLD are yet to be determined. The relationship between dietary and genetic determinants of vitamin D status and NAFLD in UK children is still unknown.

The results of the study will inform nutrition guidelines for paediatric liver disease patients and provide molecular insight into the role of vitamin D in the pathophysiology of paediatric NAFLD.

Catherine Arkley, Chief Executive of CLDF, commented: "Supporting research is a vital area of our work as this is what gives young people and their families hope for a better future. Over the past 30 years CLDF has funded over £8m of research projects, encompassing clinical, laboratory based and social research, including previous studies carried out both by the Dr Moore at University of Surrey and the Kings College Hospital paediatric team. We are delighted to be working with both teams again by funding this collaborative study which will be the first of its kind in the UK and which we hope will represent a key step forward in our understanding of NAFLD."

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