Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion—A Systematic Review

Abstract

In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.

Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion

“…The challenge for the future is to find dynamic, very specific, rapidly measurable markers able to predict postoperative complications and long-term outcome. Technical advance in laboratory technique [ 61 ], genomics markers [ 62 , 63 ], new technologies such as hyperspectral real time imaging [ 64 ] and artificial intelligence might improve pre-transplant viability assessment and expand the donor pool.…”

Obstacles to implement machine perfusion technology in routine clinical practice of transplantation: Why are we not there yet?

“…Another interesting example of the lack of clinical consensus is the high number of parameters suggested for viability assessment during MP. The absence of uniform definitions and criteria, which target donor and recipient risk factors, often considered decisive to accept an organ, leads to a high number of small, retrospective cohort studies, claiming the discovery of new viability tools, with however limited clinical relevance 11,68 . Such parameters are often not even tested in human LT.…”

Using organ perfusion to optimize donor livers

“…Although standardized criteria are still lacking, both biliary and hepatocellular injury can be evaluated during NMP. Assessment of biliary injury relies on composition of bile fluid as a surrogate for various parameters of cholangiocyte function including bile biochemistry (pH, bicarbonate), bile composition, and overall quantity of bile production [42]. Parenchymal injury is assessed using effluent lactate clearance, transaminase release, tissue oxygen consumption, ATP production, and vascular flows and macroscopic appearance [38,40,43].…”