Deep Liver Phenotyping and Immunology Study

The purpose of this study is to perform a characterisation of the cancer predisposing 'field effect' that is associated with hepatic & hepato-biliary malignancy, and, to identify minimally invasive biomarkers that may detect this field effect. This will be achieved through collection of patient samples (Tissue/Blood/Urine/Bile). Comparisons will then be made between patients with hepatic & hepatobiliary cancer and patients with chronic liver disease and also longitudinally in individual patients who either develop or are cured of hepatic & hepato-biliary malignancy during the study. The investigators hope to exploit this knowledge to develop novel biomarker candidates that may ultimately form inputs to a multi-parametric early cancer detection model. The study aims are:

• Develop a cohort of patients with HCC, cholangiocarcinoma or liver metastases and a cohort of chronic liver disease patients representing all the commonly encountered aetiologies (viral, metabolic, autoimmune and alcohol related liver disease).
• Collect samples from directly within the non-cancerous liver (FNA liver/biopsy/ablation/resection specimens), blood and urine in addition tumour tissue (resection/biopsy/ablation), bile and bile duct brushings.
• Flow cytometric & molecular biologic analysis of tissue and peripheral blood and bile.
• Transcriptomic analysis of cell populations in liver and blood.
• Genetic & molecular biologic analysis of hepatic and immune cells and secreted products.

Inclusion criteria

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged 18 years to 75 years.

Malignancy Cohort: extra inclusion criteria - Diagnosed with a malignancy or with clinical suspicion of a malignancy affecting the Liver or Biliary Tree.

Control cohort: extra inclusion criteria

• Patients with confirmed chronic non-malignant hepatobiliary disease.

Additional Inclusion Criteria for Patients Undergoing optional Liver FNA

• Willing to undergo ultrasound guided liver FNA (unless specific contra-indications to the procedure apply).
• Has undergone appropriate clinical imaging of the upper abdomen (US/CT/MRI) within the last 12 months.
• Full blood count (FBC) and coagulation profile (Coag) checked within 30 days prior to FNA procedure (Baseline Visit).

Exclusion criteria

• Unable to consent.
• Pregnancy.
• Any concern by the investigator regarding the safe participation of the patient in the study; or investigator's consideration, for any other reason, that a patient is inappropriate for participation in the study.

Additional Exclusion Criteria for Patients Undergoing optional Liver FNA (These criteria will exclude a patient from having FNA as part of the study)

• Significant comorbid medical condition(s) which may in the opinion of the investigator increase the risk of an FNA Liver.
• Coagulopathy - International Normalized Ratio (INR) >1.3, Prothrombin Time (PT) >16 seconds, Platelet count <100 x 10^3/L.
• Known bleeding disorder (e.g. Haemophilia).
• Current use of an oral/injectable anticoagulant medication.
• Current use of an oral antiplatelet agent.
• The presence of ascites.