The Concept of Functional Graft Size: An Eternal Theme of Maximizing Donor Safety and Recipient Survival in Living Donor Liver Transplantation

Abstract

Predicting the risk of graft dysfunction has been a matter of debate in partial liver transplantation. Although graft size is associated with posttransplant survival in adult recipients, previous studies have accumulated evidence of other important factors determining the fate of partial grafts, including graft quality, recipient disease severity, portal inflow, and venous outflow.1-5 The combination of these factors helps estimate functional graft size (Figure 1). However, there is not enough scientific evidence to support reliable cutoffs for each component to accurately calculate the area of the pentagon. The lack of objective measures in estimating functional graft size leaves us relying on surgeons’ experience to decide which lobe should be taken from donors. With a graft to recipient weight ratio of 0.8% being a conservative cutoff to avoid small-for-size syndrome, most transplant centers worldwide have predominantly used larger right lobe grafts rather than smaller left lobe grafts in adult living donor liver transplantation (LDLT), knowing to pose more risks on the donor.6 Further, despite the advancement in surgical techniques and graft-recipient selection over time, there is no clear consensus on when and how partial liver graft hemodynamics should be modulated. To achieve the best outcomes in adult LDLT, a precise estimation of functional graft size is critical.FIGURE 1.: Functional graft size is determined by actual graft size, graft quality, recipient disease severity, graft portal inflow, and venous outflow. The area of the pentagon represents functional graft size. *To help understand the impact of excessive portal flow in LDLT, only portal hyperperfusion is shown as an unfavorable factor for portal inflow decreasing functional graft size. Please note that hypoperfusion (eg, portal steal) also negatively impacts functional graft size, but it was omitted in this figure. BMI, body mass index; GRSVR, graft to recipient splenic volume ratio; GRWR, graft to recipient weight ratio; GV/SLV, graft volume/standard liver volume; HVPG, hepatic venous pressure gradient; LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; V5/V8, segment 5/8 vein.Now, the question is how we determine the degree of portal hyperperfusion to guide us if portal inflow modulation is necessary. Is intraoperative portal pressure or flow accurate enough to tell us whether graft inflow should be modified? Intraoperative measurement is often affected by recipient unstable systemic hemodynamics, which potentially makes portal pressure and flow data unreliable and unreproducible. In contrast, a preoperative pressure study can provide a stable measure. At Cleveland Clinic, we routinely measure preoperative hepatic venous pressure gradient (wedge hepatic venous pressure-free hepatic venous pressure) to help determine the indication for portal inflow modulation in adult LDLT because this preoperative value correlates well with the postreperfusion portal flow.7 Since actual graft size per se does not always affect transplant outcomes, experienced centers have been pushing the boundary to use smaller grafts.8 Despite the lack of consensus on reliable indicators, both preoperative hepatic venous pressure gradient and intraoperative data could provide valuable information for the safe use of small-for-size grafts. On the other hand, some centers have achieved excellent survival after LDLT without measuring any intraoperative parameters. Therefore, the answer to the best indicator for decision-making remains unknown. More importantly, even if a reliable parameter of graft hemodynamics exists, an accurate cutoff to decide whether to proceed with portal inflow modulation is hard to be generalized because each center has its own indication, donor selection, and surgical techniques. In this issue of Transplantation, Singh et al9 reported a new parameter to predict early graft outcomes in adult LDLT (n = 135). The authors demonstrated that a high intraoperative pressure gradient across the liver graft (ΔPpost: portal pressure – central venous pressure > 12 mm Hg) and low graft to recipient splenic volume ratio (GRSVR ≤ 1.15 g/cc) were predictive of early allograft dysfunction. The hyperperfusion index (HPi: ΔPpost/GRSVR), an amalgamation of both parameters, was more sensitive and specific to identify recipients who were likely to experience early allograft dysfunction (HPi ≥ 9.97 mm Hg.cc/g). Further, when an HPi was >16.25 mm Hg.cc/g, it predicted 90-d mortality with a sensitivity of 100% and a specificity of 78.9%. Of 135 patients, 96 were included in the test cohort to establish the HPi, which was validated by another cohort of 39 patients. It should be noted that no recipient had portal inflow modulation to decrease portal flow and pressure, such as splenic artery ligation, splenectomy, or portocaval shunt. However, 17 recipients (12.6%) had shunt ligation to prevent a portal steal. Based on this retrospective study, the authors concluded that HPi could increase the ability to identify high-risk patients for early allograft dysfunction and mortality after adult LDLT. To improve outcomes, HPi may help establish surgical planning for portal inflow modulation. In Figure 1, the area of the pentagon represents functional graft size in partial liver transplantation. To increase functional graft size, we may take a right lobe rather than a left lobe, consider dual graft, encourage living donors to lose weight, or optimize recipient medical condition. However, once LDLT cases are set up, actual graft size, graft quality, and recipient disease severity are hardly modifiable. On the other hand, after hard lessons learned from multiple failures in the early era of LDLT, we have borne in mind that graft hemodynamics, including inflow and outflow, must be perfect.10 Therefore, every effort to medically and surgically control portal hyperperfusion and maximize graft venous outflow will increase functional graft size to minimize the risk of graft failure. The authors’ work highlights the importance of estimating functional graft size quantitatively. The beauty of HPi is attributable to dual consideration of portal hemodynamics (ΔPpost) and actual graft size (GRSVR), which gives higher sensitivity and specificity in predicting the risk of early allograft dysfunction and recipient mortality. Since HPi needs only simple math of intraoperative pressures and sizes of a liver graft and recipient’s spleen, this parameter should be easily adopted, and center-specific cutoff values can be identified based on previous data at each center. While each component of HPi consists of a known indicator, it makes sense to see better performance of this new index with the standardization of graft hemodynamics by actual graft size. Understanding the concept of functional graft size is essential in successful LDLT but not enough to push us up to the next level. We need to find a reliable and reproducible parameter capable of quantitating functional graft size. If we know minimal functional graft size to prevent small-for-size syndrome, larger grafts are not always necessary to achieve the goal. Therefore, accurate prediction of functional graft size will ultimately help maximize living donor safety and patient survival so that we can overcome the longstanding challenge that our pioneers and colleagues have struggled with.

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