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Characterisation of the role of vitamin D in paediatric non-alcoholic fatty liver disease.

Gibson, Philippa S. (2017) Characterisation of the role of vitamin D in paediatric non-alcoholic fatty liver disease. Doctoral thesis, University of Surrey.

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Abstract

Previous research has suggested a role for vitamin D in non-alcoholic fatty liver disease (NAFLD) pathogenesis. Several observational studies have observed low vitamin D status (25OHD) with poorer histological findings. The principal aims of this study were to assess diet and lifestyle, 25OHD status, gene variants in vitamin D metabolism in UK children, and separately examine the effect of vitamin D in an in vitro NAFLD model. Dietary results from the case control study (n=32) indicated vitamin D intakes of paediatric patient with biopsy-proven NAFLD and ultrasound-cleared obese patients were 1.7μg/day and 3.5μg/day, respectively, well below the new UK recommendation. Children failed to meet current UK government recommendations for physical activity. In our UK paediatric biopsy-proven NAFLD cohort (n=103), the majority of patients presented with deficient (<25nmol/L, 25.5%) or insufficient (<50nmol/L, 80.8%) mean serum 25OHD levels. Furthermore, patients had significantly lower 25OHD levels during winter months in comparison to summer (p=0.0001) and autumn (p=0.0026), while 25OHD levels were non-significantly lower in NASH compared to non-NASH patients (p=0.0576). We observed that single nucleotide polymorphisms (SNPs) involved in vitamin D metabolism were associated with poorer liver histology grading; specifically, three SNPs were associated with increased steatosis and one with increased inflammation score in Caucasian patients. Finally, LX-2 cells, an immortalised human hepatic stellate cell line, demonstrated significantly reduced cell proliferation (p=0.0005) with increasing doses of 1α,25(OH)2D3 after 10 days of incubation in clonogenic assays. In conclusion, we found that NAFLD children have extremely low levels of 25OHD throughout the year, with little dietary contribution. In addition, several vitamin D related SNPs were associated with poorer histological findings. These novel data suggest an important role for vitamin D in the pathogenesis and progression of NAFLD in a paediatric population.

Item Type: Thesis (Doctoral)
Subjects : Nutrition, molecular biology, diet, liver disease, paediatric, vitamin D
Divisions : Theses
Authors :
AuthorsEmailORCID
Gibson, Philippa S.UNSPECIFIEDUNSPECIFIED
Date : 28 February 2017
Funders : Children's Liver Disease Foundation, Institute of Liver Studies, King's College Hospital
Contributors :
ContributionNameEmailORCID
Thesis supervisorMoore, J. BernadetteUNSPECIFIEDUNSPECIFIED
Thesis supervisorHart, Kathryn H.UNSPECIFIEDUNSPECIFIED
Thesis supervisorLanham-New, Susan A.UNSPECIFIEDUNSPECIFIED
Depositing User : Philippa Gibson
Date Deposited : 09 Mar 2017 12:29
Last Modified : 09 Mar 2017 12:29
URI: http://epubs.surrey.ac.uk/id/eprint/813394

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