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Multicenter Matched-pair Analysis of Extended Right Lobe Versus Whole Organ Liver Transplantation: A Snap Shot of the Tragic Situation in Germany

Herden, Uta MD1; Nadalin, Silvio MD2; Scherer, Marcus N. MD3; Mehrabi, Arianeb MD4; Braun, Felix MD5; Paul, Andreas MD6; Gül-Klein, Safak MD7; Pratschke, Johann MD7; Fischer, Lutz MD1

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doi: 10.1097/TP.0000000000003982
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Split liver transplantation (SLT) offers the potential for expanding the limited deceased donor pool. Whereas outcomes of SLT in the pediatric population are generally considered positively, there are concerns regarding increased complications, especially biliary problems of right-extend liver transplantation (ERLT).1,2 Limiting liver splitting to optimal donors using a standardized technique may enable equivalent results of ERLT and whole liver transplantation (WLT).

The technique of partial liver transplantation was developed by R. Pichlmayr in the 1980s.3 After initial trials and a clinical learning curve, SLT was established in Germany as a standard procedure, applied in-situ by experienced transplant surgeons who either performed the splitting procedure in the donor clinic or, alternatively, the ex-situ application for liver transplants that were shipped to recipient hospitals. As a rule, during the initial period, both split grafts (right extended and left lateral) remained in the splitting center. Later, in early 2000, it was decided in Germany that the extended right graft will no longer be allocated to the splitting center but rather undergo a nationwide Model for End-stage Liver Disease (MELD)–based allocation to avoid a preference for centers or patients. This approach resulted in a second transport and thus a prolonged ischemic time.

Notably, only highly selected organs of excellent quality are used for ERLT. On the background of a significant recent deterioration of available donors in Germany,4 we hypothesized that the outcome after ERLT from optimal donors should compare favorably to that of WLT. Particularly, we were interested in testing if the change in allocation policy leading to prolonged cold ischemic time (CIT) and possibly further organ damage in ERLT may affect transplant outcomes. Against this background, we conducted a retrospective study in 7 large transplant centers in Germany between 2007 and 2015. A 1:1 matched-pairs analysis of 121 patients with ERLT and WLT each was done. Matching criteria included (1) recipient age, (2) recipient calculated MELD score, and (3) donor age.

Notably, ischemic times in the ERLT group increased by approximately 2.5 hours. Regarding surgical outcome, biliary and vascular complications were comparable following ERLT versus WLT. Likewise, overall patient mortality was comparable (17.4% with 21 patient deaths after ERLT and WLT each). Interestingly, in the early postoperative period (by 3 mo) patient mortality was higher after ERLT compared with WLT. With regard to the causes of death, organ failure with infectious complications, often associated with primary non function, dominated in the ERLT group. Additionally, statistical analysis revealed a significant reduction of graft survival for right-extended splits compared with whole organs (Figure 1). This difference in organ survival was distinctly amplified in the subgroup of patients transplanted with a high MELD score (≥30 points) (Figure 2).

F1
FIGURE 1.:
Graft survival whole organ vs right-extended split liver transplantation (LT). The figure shows the graft survival of the matched-pairs cohort (whole organ vs right-extended split LT, n = 121 per group) illustrated by Kaplan-Meier survival curves. There was a significant reduced graft survival following right-extended split LT compared to whole liver transplantation (Log-rank test P = 0.046).
F2
FIGURE 2.:
Graft survival whole organ vs right-extended split liver transplantation (LT) in recipients calculated MELD score ≥30 points. The figure illustrates the graft survival in patients with a high MELD score at the time of transplantation (MELD score ≥ 30 points; n = 52 patients). There was a clearly reduced graft survival following right-extended split LT compared to whole organ (Log-rank test P = 0.077). MELD, Model for End-stage Liver Disease.

Liver allocation in Germany is based on urgency using the MELD score.5 In clinical practice, liver splitting (generally ex-situ) is performed by the transplant center for a small child as the primary recipient, if the graft quality is estimated of appropriate quality. There are no clearly defined splitting criteria or mandatory splitting policies for high-quality organs and also no incentives for the specific center performing liver graft splitting. The remaining right-extended graft then undergoes formal MELD allocation within Germany or in selected cases in the entire Eurotransplant region6 resulting into prolonged ischemic times. In our cohort, ERLT showed a worse graft survival than WLT resulting into higher early mortality in the ERLT group. In particular, ERLT recipients with high MELD scores demonstrated an increased risk of primary non function and early mortality. We postulate that the interplay of several factors may explain the inferior outcomes of ERLT observed in our study, despite the use of organs from high-quality donors. The graft quality decreases as the splitting procedure creates an anatomic variant graft. Further damage of the graft occurs due to prolonged CIT with an extended transport time due to the formal allocation of the ERLT graft. In detail, in our study, the mean CIT in ERLT was 2.5 hours above the CIT in WLT resulting into an average of 13 hours. As split liver transplants are more technically demanding, they are also more vulnerable to secondary hits such as prolonged CIT and postoperative complications in severely ill recipients.7 Because of these factors, the early postoperative period after SLT is most critical which seems to be particularly true for recipients with high MELD levels.

In our opinion, it is essential to improve the logistics of SLT in Germany to reduce CITs. In a recent analysis of 64 adult recipients who received an ERLT at the University Medical Center Hamburg-Eppendorf,8 we found that grafts after external splitting with subsequent shipping to our center had a significantly longer ischemic time and compromised outcomes compared to ERLT after in-house splitting. Besides internal splitting with both split parts remaining in the same center, several other options could be considered: in situ splitting in the donor hospital followed by parallel shipping of split grafts to 2 recipient centers, sharing of splits within a regional network reducing travel distances for the second split, and, once established, the use of machine perfusion to abrogate the negative consequences of prolonged ischemic times. All of these options require adjustments with regard to legal, administrative, and logistical issues as well as human and hospital resources. However, at a time of organ shortage, when split liver transplants offer the opportunity to increase the number of transplants, every effort must be made to ensure the optimal outcome of these valuable transplants.

In conclusion, with the introduction of MELD-based allocation of right-extended grafts causing long CITs outcomes have been inferior. As a result, liver splitting enables pediatric liver transplant but shows results that, because of the logistics implemented in Germany, are well below expectations that can be anticipated from these high-quality transplants—in our opinion, a tragedy at times when every effort should be made to increase organ availability and to improve outcomes.

REFERENCES

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