Personalising immunosuppression in liver transplantation

This prospective observational cohort study aims to determine the utility of combining two novel blood tests - quantiferon monitor and donor specific cell-free DNA (QFM-dscfDNA) - in monitoring and managing immunosuppression post liver transplantation (LT). Liver function tests (LFTs) are extremely sensitive tests for organ injury but have poor specificity for LT complications. As a screening tool, they can lead to a series of radiological and endoscopic investigations that often culminate in an invasive liver biopsy to confirm the clinical event. Researchers at Austin Health have therefore pioneered the study of two rapid and low-cost blood tests in LT: QFM which measures the immune function of the recipient, and dscfDNA which quantifies injury to the donor organ. For this study, adults (aged 18 years and older) undergoing LT at a tertiary hospital will be invited to participate in this study in the inpatient and outpatient setting. Study co-ordinators (clinicians who are not members of the treating team) will meet with potential participants face-to-face and provide them with written information about the study. Participants who provide written informed consent will be followed up for 12 months and will be required to have serial additional blood sampling. This will be performed by experienced phlebotimists when blood tests for the standard of care for LT occur wherever possible, to reduce the need for additional venesection. 15-30ml of blood will be collected to perform QFM-dscfDNA testing and be stored for future research purposes. Blood sampling will occur pre-transplantation and post-transplant on day 1, 3 and 5; week 1 and 2; month 1, 2, 4, 6 and 12. If an episode of treatment responsive biopsy proven acute rejection (tBPAR) or infection occurs, blood sampling will occur and at three timepoints 1-3 days apart to capture QFM-dscfDNA dynamics. All samples will be batched for analysis at the end of the 12-month follow-up, so results will not influence the decision-making of the treating clinicians. In the event that a patient is unwell and unable to consent (which may happen for example in fulminant hepatic failure), consent for initial enrolment will be obtained from the next of kin/medical treatment decision maker. Following recovery from the LT, patient consent for ongoing follow up and for use of data collected at enrolment will be obtained. If the patient wishes to withdraw the consent obtained from their next of kin/medical treatment decision maker, all of the data collected for research purposes will be destroyed.