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The Barnes group works on a range of projects related to liver pathology:

Liver cancer early detection

The DeLIVER technologies: TAPS, Host & viral genetics, immune analysis, advanced imaging, 'omics & protein biomarkers

Liver cancer, of which hepatocellular carcinoma (HCC) is the commonest form, is a major global health problem, with 854,000 new cases and 810,000 deaths/year. Liver cancer is the fastest rising cause of cancer death in the UK in part due to predominantly late-stage diagnoses when current treatments are not effective. Earlier detection improves survival and strategies to achieve this are focused on patient groups with conditions that increase the risk of HCC development, such as cirrhosis.

The CRUK-funded DeLIVER programme is characterising the pre-cancerous liver microenvironment and integrating multi-modal technologies to develop and refine strategies for translatable liver cancer risk prediction and early detection. The DeLIVER team are using state-of-the-art multiparametric imaging, host and viral genetics, and liquid biopsy technologies, such as Dr Chunxiao Song’s TAPS technology, to identify the earliest indications of HCC by studying people at high-risk of developing HCC over several years and those with early HCC.

We are also working on a collaborative programme in Pakistan to identify cancer-associated genotypes of hepatitis C to improve assessment of liver cancer risk. A cohort of ~500 individuals with HCV-associated liver cancer is being recruited and samples are being collected for viral whole genome sequencing. Working with Dr Azim Ansari (Nuffield Department of Medicine), we will analyse these sequences, comparing to people with HCV infection but not cancer, to identify any genetic patterns that are linked to cancer.

Vaccines against hepatitis

We are developing T cell pan-genotypic vaccines for hepatitis C virus (HCV) prevention and hepatitis B virus (HBV) cure using simian adenoviral and other viral vectors. A major challenge for HCV vaccine development is the significant viral diversity both within the same host and between hosts – though parts of the viral genome are conserved making these excellent T cell targets in the context of a T cell vaccine. Some of the technologies we are developing include integral genetic adjuvants that will have applicability in a broad range of diseases.

IgG4-related disease

Immunoglobulin G4-related disease (IgG4-RD) is a condition that causes inflammation that can affect many different organs. The pancreas is most commonly affected, followed by the bile ducts in the liver, the salivary glands and the kidneys. It is difficult to diagnose as there is no single test and although treatment with steroids is effective, better treatments that prevent relapse are needed. We are involved in the Oxford IgG4-RD study, which aims to discover the pathways that lead to IgG4-RD and find out what happens to patients with IgG4-RD in order to develop better diagnostic tests and treatment.

 

An overview of the trials involved in the Oxford DeLIVER program, including the Pearl, Selina and DELPHI trials.