Liver transplantation: Current status and challenges

Table 1 Comparison of hypothermic and normothermic mechanical perfusion

	Hypothermic mechanical perfusion	Normothermic mechanical perfusion
Temperature	4 °C	37 °C
Pathophysiology	Reduced cellular metabolism	Continued cellular metabolism
	Non-functioning liver during preservation	Functioning liver during preservation
Perfusate	No specific requirements, oxygen can be used	Continuous delivery of nutrients and oxygen needs to be maintained
Logistics	Similar to that of hypothermic mechanical perfusion currently used for renal allografts	More complex
Benefits	Logistically easier	Allows for the assessment of metabolic and synthetic function during preservation
	May provide benefit in marginal livers	May provide benefit in marginal livers
		Potential use in steatotic livers
		Felt to reduce ischemia reperfusion injury

Table 2 Current data for donor-specific HLA-antibody-associated injuries in kidney and liver transplantation

	Kidney transplantation	Liver transplantation
DSA specificity and levels	↑ risk hyperacute rejection[44]; ↑ DSA in new onset late kidney allograft dysfunction[45]; acute AMR is associated with high posttransplant DSA levels[45]	↑ DSA in recipients with CR, presence of IgG3 subclass associated with ↑ risk of graft loss[40]
C4d deposition in microvasculature	Graft failure significantly worse in the presence of C4d+ staining[44]; C4d+ is a marker of antibody-mediated injury[44,46]	C4d+ staining nonspecific; In the presence of DSA, linear portal capillary and sinusoidal staining observed in ACR; DSA negative C4d+ staining found in biliary strictures and recurrent liver disease[47]
DSA subtypes, C1q binding	↓ graft survival and ↑ risk for AMR with C1q-binding DSA[48,49]	Limited data[50]
Microvascular inflammation	Peritubular capillaritis is a possible predictor of chronic AMR[51]; subclinical AMR may contribute to development of CAN[52]	No current data
EC activation by light microscopy	EC and BM ultrastructural abnormalities in glomerular and peritubular capillaries are early markers of TXG[53]	No current data
Gene expression profile of chronic AMR	Defined genetic profile in AMR[54,55]	No current data
Therapeutic-trials to prevent DSA-associated injury	Bortezomib (plasma cell-targeted therapy) as a possible antihumoral therapy[56]; plasma exchange for AMR[57,58]	No current data

Modified from Ref. 43. AMR: Antibody-mediated rejection; CAN: Chronic allograft nephropathy; EC: Endothelial cell; BM: Basement membrane; DSA: Donor-specific HLA-antibody; TXG: Transplant glomerulonephropathy.