تفاصيل المشروع
Abstract English
Background
Non-alcoholic fatty liver disease (NAFLD) is a major global driver of liver related morbidity and mortality. As metabolic complications of obesity increase the incidences of hypertension, diabetes and renal disease, NAFLD is similarly increasing in incidence. In Kuwait NAFLD is becoming the single largest cause of liver disease requiring transplant. The progression from NAFLD to hepatitis and fibrosis is not well understood and molecular markers aiding the clinical diagnosis and treatment are lacking. The purpose of this study is to identify genetic triggers and risk factors as well as metabolic regulatory exosomes associated with NAFLD.
Methods
We will define the pathogenesis of NAFLD / NASH through the investigation of ggenetics by performing whole genome sequencing on all recruited patients, targeted analysis of rare variants contribute to NAFLD and if patient numbers reach 1000 or more, then we can perform genome-wide association studies. Mitochondrial bioenergetic efficiency (FACS/OROBOROS) and test effect of therapeutic exosome using ex vivo human steatotic liver model using Organox device. Metabolomic profiling on patients will be carried out to define and will allow the assessment of functional microbiomics. The role innate, innate-like, and adaptive immune cells in NAFLD pathogenesis by screening for immunoregulation impairment: by assessing the frequency of and functional capacity of CD4posCD25highFOXP3pos regulatory T cells (Tregs) and regulatory B cells and measure the peripheral inflammatory burden by screening for a 54 serum biomarkers of immune activation. Patient undergoing surgical intervention, animal models and ex vivo machine perfusion using OrgaNox device
We expect to define the incidence of NAFLD in Kuwait ad to define the genetic, metabolic and immunological signatures changes in NAFLD on a cellular and tissue level and to evaluate the influence of surgical intervention / medical therapy on disease progression.
Non-alcoholic fatty liver disease (NAFLD) is a major global driver of liver related morbidity and mortality. As metabolic complications of obesity increase the incidences of hypertension, diabetes and renal disease, NAFLD is similarly increasing in incidence. In Kuwait NAFLD is becoming the single largest cause of liver disease requiring transplant. The progression from NAFLD to hepatitis and fibrosis is not well understood and molecular markers aiding the clinical diagnosis and treatment are lacking. The purpose of this study is to identify genetic triggers and risk factors as well as metabolic regulatory exosomes associated with NAFLD.
Methods
We will define the pathogenesis of NAFLD / NASH through the investigation of ggenetics by performing whole genome sequencing on all recruited patients, targeted analysis of rare variants contribute to NAFLD and if patient numbers reach 1000 or more, then we can perform genome-wide association studies. Mitochondrial bioenergetic efficiency (FACS/OROBOROS) and test effect of therapeutic exosome using ex vivo human steatotic liver model using Organox device. Metabolomic profiling on patients will be carried out to define and will allow the assessment of functional microbiomics. The role innate, innate-like, and adaptive immune cells in NAFLD pathogenesis by screening for immunoregulation impairment: by assessing the frequency of and functional capacity of CD4posCD25highFOXP3pos regulatory T cells (Tregs) and regulatory B cells and measure the peripheral inflammatory burden by screening for a 54 serum biomarkers of immune activation. Patient undergoing surgical intervention, animal models and ex vivo machine perfusion using OrgaNox device
We expect to define the incidence of NAFLD in Kuwait ad to define the genetic, metabolic and immunological signatures changes in NAFLD on a cellular and tissue level and to evaluate the influence of surgical intervention / medical therapy on disease progression.
| الحالة | منتهي |
|---|---|
| تاريخ البدء/النهاية الساري | 1/05/23 → 1/05/25 |
الشركاء المتعاونون
- Kings College London
بصمة
استكشف موضوعات البحث التي تناولها هذا المشروع. يتم إنشاء هذه الملصقات بناءً على الجوائز/المنح الأساسية. فهما يشكلان معًا بصمة فريدة.