Chronic Liver Disease, Somatic Mutation
Conditions
Keywords
Somatic mutations liver
Brief summary
Deaths from chronic liver disease are rising in the UK and around the world. The leading causes are alcohol-related liver disease, metabolic-dysfunction associated steatotic liver disease (MASLD, formerly known as 'non-alcoholic fatty liver disease') and viral hepatitis. Chronic liver disease puts people at significantly increased risk of liver cancer, which in the UK has a 5 year survival of under 15%. Little is understood about how liver cells acquire genetic changes, called somatic mutations, as they progress from healthy cells, to disease, to cancer development. This study aims to investigate these somatic mutations across different causes of chronic liver disease, and different stages of liver disease. The investigators hope this will help us to understand how different insults to the liver put the liver cells under different pressures, resulting in varying genetic changes. By understanding these changes specific to disease aetiology and stage, novel genetic targets may be identified which assist to focus research in identifying specific prognostic, diagnostic and therapeutic tools in chronic liver disease, and improve outcomes for patients. Tissue, surplus to clinical requirement, from patients were undergoing liver biopsy, liver resection or liver transplantation (tissue sampling from explanted liver) collected by collaborators at University of Texas Southwestern will undergo genomic sequencing at the Wellcome Sanger Institute.
Interventions
OTHERNo intervention
This study utilises pre-collected samples only.
Sponsors
The Wellcome Sanger Institute
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-collected cohorts of liver tissue collected from adults (male and female) with consent and ethical approval for use in research.
Exclusion criteria
Anything outside of the above including samples other than liver tissue, samples where there is no consent or ethical approval for use in research and/or samples from children.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Somatic mutations in chronic liver disease | 2 years | Metrics evaluated include the number of somatic mutations, the spectrum of mutational signatures (encompassing base substitutions, indels, genome rearrangements, and copy number changes), and the size and relatedness of clonal populations within liver tissue samples. These collective analysis of these metrics will aim to identify and quantify variations that may contribute to disease development and progression. |
Countries
United Kingdom
Outcome results
None listed