Omics-based Predictors of NAFLD/Potential NASH

Summary

The cascade of care for the non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) requires crossing the barriers for their diagnosis and treatment. The multifactorial nature of NAFLD/NASH limits their diagnosis by a single factor solely. This project aimed at developing a powerful composite marker panel based on multi-omics technologies to detect NAFLD without or with fibrosis (potential for NASH) in high-risk populations (obesity, type 2 diabetes, hypertensive, dyslipidemia). This project is an exploratory study to unrevealing the intra-heterogeneity and inter-similarities of NAFLD without and with fibrosis versus those of healthy individuals. The molecular and clinical characteristics of 450 participants (225 adults aged 30-60 years and 225 children aged 12 -18 years) will be investigated; 150 NAFLD patients without, 150 NAFLD patients with fibrosis (potential NASH) compared to 150 healthy individuals. Detection of genetic polymorphism of SNP of 10 gene variants involved with NAFLD without and with fibrosis, gene discovery and molecular diagnosis of dyslipidemia using next-generation sequencing and whole-exome sequencing (genomics), the expression level for the top 5 of 168-panel genes of plasma miRNAs (epi-genomics), the glycosylation pattern of five glycoproteins (proteomics), salivary analysis of ten microbiomes and five microbial-related metabolites (metabolomics) will be investigated. Eventually, the development of precision therapies to target NAFLD without and with fibrosis and possibly reverse fibrosis could be achieved.

Conditions

• Non-Alcoholic Fatty Liver Disease
• Non Alcoholic Steatohepatitis

Interventions

DIAGNOSTIC_TEST

Genomics (DNA Extraction)

Blood samples for detection of: Genes for Dyslipidemia BY WES and NGS (4 GWA) (30 cases) Genes polymorphism for NAFLD/NASH BY TaqMan SNP Genotyping Assay on 10 GWAS

DIAGNOSTIC_TEST

Epi-genomics

* blood samples for detection of Expression profiling of plasma microRNAs * PCR array to determine the altered miRNAs for 168 plasma miRNAs (12 cases) * Expression analysis of top 5 altered miRNAs (All)

DIAGNOSTIC_TEST

Proteomics (Glycoproteomics)

blood samples for Identifying glycosylation pattern of five glycoproteins linked with NAFLD/NASH (transferrin, apoC III, haptoglobin, Mac2 binding protein, IgG)

DIAGNOSTIC_TEST

Salivary Metabolomics

Salivary Samples for detecting Salivary Metabolomics 1. Genome analysis (Identification of microbial strains common among Egyptians BY apid RT-PCR (DNA sequencing: 16S rRNA gene amplicons) 2. Microbiome related Metabolites Identification using GC-MS Analysis (the top 5 identified microbial-related metabolites) as metabolomics 3. Meta-genomic assess of three microbiome-related metabolites; lactoferrin, (LPS), (IgA) BY Commercial ELISA kits

BEHAVIORAL

Individualized counselling for behavioural modification

Individualized counselling for behavioral modification (3 sessions): Nutritional education, Promotion of physical activities and Cognitive \& Psychological support

Sponsors & Collaborators

• National Research Centre, Egypt

  lead OTHER

Principal Investigators

• Ammal M Metwally · National Research Centre of Egypt

Eligibility

Min Age

12 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-01

Primary Completion

2023-12-30

Completion

2024-04-30

Countries

• Egypt

Study Locations