The main result of the present study is that neither the FAP patients donating their livers for domino procedure nor the recipients of FAP liver grafts are exposed to any significant additional operative risk compared to their counterparts i.e. FAP patients not donating their livers and deceased donor liver recipients, respectively.
Study of FAP liver donors versus FAP nonliver donors
The explant technique of the FAP liver donor is modified compared to the standard surgical technique for a diseased liver. This modification should not, for evident ethical reasons, carry an additional risk for the FAP liver donor. The principal technical caveat in removing an FAP liver for domino transplantation is in the sectioning of the suprahepatic vena cava. To prevent hepatic outflow obstruction, an adequate caval length for both the donor as well as the FAP liver graft (to be transplanted) is necessary. As mentioned earlier, to achieve an adequate caval length several modifications have been described (27–30). In our series, we did not have to use any modification to deal with the vena cava during domino LTs. However, when transplanting FAP patients with grafts without vena cava (living related LT or split graft without the vena cava) these reconstruction techniques were very useful in our experience (data not shown). Concerning the rate of complications (caval outflow obstruction or Budd–Chiari syndrome), in our series only one FAP donor developed venous outflow occlusion requiring retransplantation.
Another important aspect is the presence of autonomic dysfunction as well as cardiovascular alterations (arrhythmias and conduction abnormalities due to cardiac amyloid infiltration) in FAP patients (33–35). To deal with these specific problems, two strategies can be used: first, the application of percutaneous veno-venous bypass (36–38), and second, the preservation of the retrohepatic vena cava. In this series (consisting of whole domino liver grafts), we used veno-venous bypass in two specific circumstances: (1) hemodynamic and/or splanchnic intolerance to porto-caval clamping; and (2) in patients with pace makers (24 cases). It is worth noting that there was no morbidity related to the bypass and although the veno-venous bypass use was more frequent in the FAP donor group, the CIT (p = 0.1), duration of operation (p = 0.73) and the number of blood units transfused (p = 0.29) were similar for both groups, a finding which is different from other reported experiences (39).
On the other hand, the preservation of the retrohepatic vena cava is an alternative strategy to veno-venous bypass (40–45). In order to use (implant) the FAP graft obtained by this technique additional retrohepatic vena cava reconstruction is needed. Recently, Escobar et al. (39) evaluated the influence of the explant technique on the hemodynamic profile during domino LT by comparing a group of 20 FAP liver donors undergoing total hepatectomy including the vena cava with veno-venous bypass to a group of 16 FAP liver donors undergoing hepatectomy with preservation of the vena cava. The authors demonstrated that the two groups were similar in terms of intraoperative hemodynamic profile. In addition, during the postoperative period the incidence of cardiovascular events and of acute renal dysfunction was similar in both groups. In summary, both explant techniques i.e. standard technique with veno-venous bypass and vena cava preservation without bypass can be safely used, and the choice finally depends on the surgeon's preference.
As mentioned earlier, from a technical point of view, arterial, biliary, portal and outflow complications occurred with similar frequency in both groups (p = 0.6, 1.0, 0.2 and 1.0 respectively). Among these complications, hepatic artery thrombosis (HAT) is the most common thrombotic event in the early post-transplantation period with an incidence ranging from 2.5% to 5% (46, 47). The incidence of early HAT in our study was 3.3% in FAP liver donors and 1.8% in FAP liver recipients, lower than rates reported by most series evaluating adult patients. While, in the literature several surgical (47–50) and medical factors (47, 51, 52) have been shown to be linked to early HAT, it is interesting to mention one puzzling risk factor recently reported by Bispo et al. (53). In their study involving 223 liver transplants (86 for FAP) in 213 patients, the investigators demonstrated that the incidence of early HAT in FAP patients was 7.7-fold higher compared to non-FAP patients. In the multivariate analysis, FAP was the only independent factor to be associated with an increased risk of early HAT. In our study, we could not demonstrate such relation.
On the other hand, we found pre- and postoperative differences between the two groups. For instance, the waiting time for the FAP donors was longer compared to the nondonor group. This finding reflects the trend of a longer waiting time for LT in general observed in the last decade. Also, the FAP nondonor group received liver grafts from younger donors compared to their donor counterparts. These differences are not surprising given the fact that the nondonor patients were transplanted during an earlier period of time marked by younger deceased donors. In contrast, at the present time, organs from elderly donors are increasingly being used by transplant units (54,55). In this context, we believe that our findings are a reflection of the current donor trends in Europe and United States (54,55). Concerning the intraoperative differences, we found that all 61 (100%) FAP donor cases had the vena cava replaced compared to 12 (30.8%) patients in the nondonor group (p < 0.001). Lastly, the rejection rate among the FAP nondonors was significantly higher compared to FAP donors. Again, this difference is related to the period of transplantation. The FAP nondonor patients were transplanted during the cyclosporine A era. At present, drugs such as tacrolimus or mycophenolate mofetil often administered in combination have been very effective in reducing the incidence of acute cellular rejection (56,57). Considering that the majority of our FAP donors received these two drugs as their standard maintenance regimen, we can assume that the observed lower rejection rate in the later group is probably due to the introduction of these immunosuppressive regimens.
Study of FAP liver recipients versus deceased donor liver recipients
The safety of the recipient is another important aspect of domino LT. The procedure should not add any significant additional risk to the recipient compared to the risk associated with conventional deceased donor liver transplantation (DDLT). Our experience, shown in Table 6 is quite explicit—the operative safety and early outcome for FAP liver recipients were not compromised. Therefore, patients receiving FAP grafts would benefit from the short waiting time for transplantation.
In conclusion, the domino procedure does not add any significant risk to neither the FAP donor nor to the FAP liver recipient. This procedure is characterized by a very good graft function and low PNF rates. In addition, it has an associated morbidity and mortality related entirely to the recipient's pathology. Lastly, domino liver grafts increase the pool of available organs in an era of donor shortage, in turn allowing transplantation of marginal recipients that otherwise would be denied standard deceased donor LT.