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.
Study Type
OBSERVATIONAL
Enrollment
250
This study utilises pre-collected samples only.
Wellcome Sanger Institute
Cambridge, United Kingdom
Somatic mutations in chronic liver disease
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.
Time frame: 2 years
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