Gastrointestinal diseases are a major cause of ill health. Blood tests called liver function tests (LFTs) are commonly performed in clinical practice. Bilirubin is part of the LFTs panel, and is an important chemical as it prevents damage to the cells in our body. Some studies have suggested that higher levels of bilirubin may prevent and be protective (after subsequent diagnosis) in certain cancers (e.g. in the lung and colon) and inflammatory disorders (e.g. fatty liver disease). Other LFTs such as GGT, ALT & AST are associated with inflammation and cancer in the liver and gut. We will compare bilirubin levels (and other LFTs) with these conditions within a large database containing anonymised electronic health records. These findings may lead to the discovery of drug targets that alter the levels of these liver products and the pathways regulating them in our body.
Liver function tests (LFTs) are commonly performed in clinical practice and are often associated with malignant and inflammatory diseases. Bilirubin, a natural anti-oxidant, is inversely associated with lung and colorectal cancer, chronic obstructive airway disease (COPD), and atherosclerosis. Other liver enzymes (e.g. GGT, ALT, AST) have been associated with inflammatory disorders such as fatty liver disease and hepatobiliary malignancy.
We will use linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER programme), [1] to investigate associations of LFTs with all common gastrointestinal disease and malignancies. We include people aged 18 or older with no underlying gastrointestinal disease at baseline, and use Cox models to estimate cause-specific hazard ratios (HRs) for the association of LFTs (Bilirubin, ALT, AST, GGT, ALP) with the first occurrence of gastrointestinal malignant and inflammatory disease. We will further compare outcomes of gastrointestinal malignant disease including mortality, disease free survival after curative and non-curative treatment.
Incidence, progression, and recurrence of 5 most common extra-intestinal cancers and death (all causes) will be important secondary outcome measures.
Identical analysis with toxins metabolised by the liver (lipids, triglycerides) will be performed.
Harry Hemingway - Chief Investigator - University College London ( UCL )
Constantinos Parisinos - Corresponding Applicant - University College London ( UCL )
Arturo Gonzalez-Izquierdo - Collaborator - University College London ( UCL )
Spiros Denaxas - Collaborator - University College London ( UCL )
HES Admitted Patient Care;NCRAS Cancer Registration Data;ONS Death Registration Data;Practice Level Index of Multiple Deprivation