Indocyanine Green Clearance Test in Liver Transplantation: Defining Cut-off Levels for Graft Viability Assessment During Organ Retrieval and for the Prediction of Post-transplant Graft Function Recovery

Liver transplantation (LT) is the gold standard treatment for end-stage liver diseases. The success of LT and the expansion of medical conditions that are successfully treated with LT, has caused a growing gap between available organs and patients still dying while awaiting a transplantable organ. Various attempts at fulfilling the gap continue to be made, including donation from live donors, split livers, and utilization of "marginal" deceased donors (e.g. elderly donors, steatotic grafts, donors after cardiac death, etc.). Marginal grafts carry an increased risk of post-transplant failure which is difficult to quantify. Yet, we rely on the donor surgeon's evaluation based on experience. In selected cases, a liver biopsy can be used, however the limitations of liver biopsies in graft viability assessment are well known and extensively questioned in the scientific literature, to the point of being used only in few selected cases by many transplant units. The adoption of an objective measure of graft viability is highly desirable to prevent from transplanting organs at high risk of failure. Similarly, the recovery of organ function after LT is not measured by means of an objective test. This is mainly monitored with laboratory tests, in some cases measuring bile production, and monitoring the clinical evolution of patients condition.

Indocyanine green clearance test (IGT) has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and is commonly used as part of the preoperative work-up before liver resections. Indocyanine green is administered intravenously, up-taken almost exclusively by hepatocytes and excreted unprocessed in the bile ducts. The disappearance rate from the bloodstream is measured either on a blood sample (i.e. retention rate 15 minutes after injection) or - more recently - with a pulsidensitometric method (i.e. plasma disappearance rate). Slower plasma disappearance rate (PDR) correlate with worse liver function. A cut-off PDR level of >14%/min has been reported to allow safe major liver resections.

The role of IGT in LT has not been investigated extensively yet, in particular for the assessment of graft viability during donation. A correlation between graft steatosis and IGT in the donor has been observed whilst an increased incidence of graft failure has been reported with PDR<11%/min. Conversely, there is more evidence in the recipient setting, with IGT correlating with the occurrence of post-LT complications (PDR cut-off level for increased risk of post-LT complications of <12.85%/min or graft loss and/or patient death of <9.6%/min). However, a correlation between the changes in the values (i.e. the slope) of IGT and graft function recovery has not been studied yet. Since recent technology enables PDR to be measured non-invasively at the bedside, this parameter is an attractive addition to liver function assessment. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required.

Hyphotesis and Significance:

We hypothesize to identify an IGT cut-off level to aid the retrieval surgeon in the decision-making process of accepting an organ to be used for LT. Secondly, we hypothesize to identify a correlation between IGT values and post-transplant organ function recovery.