Lowering the age limit for "split-able" liver grafts is a potential strategy to increase donor availability for pediatric patients. Whether pediatric donors be used in SLT and the youngest donor age that can be considered for SLT have remained unclear. In this study, we reported the safe use of pediatric donors <7 years in SLT in children. The youngest donor was 2.7 years old; as far as we know, this is the youngest donor who has been reported in SLT.
Splitting liver grafts from pediatric donors is a potential strategy to provide organs for children and to decrease waitlist mortality, especially for patients <1 year old or weighing <6 kg. Most studies concentrated on the upper age limit of the donors for SLT;[8,13] the appropriate lower donor age limit for SLT has not been well defined, with previous studies suggesting that donors <10 years old or weighing <40 kg should not be considered.[2,14] With the progress in surgical skills and perioperative patient care, Cescon et al[15,16] demonstrated that the use of donors <10 years old or weighing <40 kg in SLT provided comparable outcomes compared with other pediatric recipients using adult split-graft donors. Nevertheless, the lower age limit for "split-able" liver grafts remains unknown.
Based on our clinical experience, we have established the criteria in selecting potential "split-able" liver grafts. Ideally, grafts meet all the criteria will be considered for split; however, grafts with only 1 missing criterion may also be considered if the donor is well controlled. This strategy is in accordance with a previous report showing that 1 missing criterion leads to a 43% increase of liver graft availability. Five of the 8 donors had 1 missing criterion, and 2 liver grafts had a longer cold ischemia time than given in our criteria. However, the recovery of liver function in these recipients (recipients 1, 2, 11, and 12) was slower than that of other recipients, liver biopsy of grafts from recipient 1 and 2 indicated ischemic and hypoxic changes. Although a liver biopsy was not performed in recipients 11 and 12, one of the patients developed cholangitis after operation and the other patient had slow recovery of biliary function. These results supported a recent study showing that prolonged cold ischemia time was associated with inferior graft recovery in SLT. Thus, a more cautious evaluation should be given to assess potential "split-able" liver grafts with a long cold ischemia time. In addition, 3 donors had a longer ICU stay before organ procurement than given in our criteria. The donors were well evaluated with a special focus on the risk of infection during their ICU stay, and the decision to use these donor livers for a split was made after multiple tests confirmed that the patients were free from pathogen infection and the patient conditions met all the other criteria for SLT. The 6 recipients receiving these liver grafts had a smooth recovery after transplant. Although the length of ICU stay is not considered in some transplant centers to determine potential "split-able" liver grafts,[6,17] we still take this factor into consideration because longer ICU stay may be related to nosocomial infection or hemodynamic disorder, and pediatric recipients are more vulnerable to this kind of injury.
One of the features of our study was that except for donor 4, all of the split procedures were performed ex situ. Some of grafts were transported to our center from other cities, which does not allow us to perform the split process in situ. Our results support other studies showing that ideal recipient outcomes could be achieved when the liver grafts were split ex situ.[19,20] Two reasons may be the cause of the remarkable outcomes: first, unlike adult grafts, the pediatric grafts were usually free of other underlying liver disease, such as steatosis; and, second, all of the donors were brain death donors with negligible warm ischemia time.
To validate the feasibility and safety of our split procedure, we further compared the outcomes of recipients receiving the LLS and ERLs. The levels of ALT and AST were significant higher in ERL recipients in the early postoperative days. One of the concerns of using ERL was the viability of segment IV because the lack of blood supply in segment IV may affect liver function. The ischemic changes in segment IV may cause hepatocyte necrosis and induce the transient release of ALT and AST; this is why the difference was seen in ALT and AST but not in TBIL. The difference vanished at the end of first week after transplant, and the postoperative complications did not differ between LLS and ERL recipients. Our study results are in accordance with other reports showing that the ischemic changes in segment IV did not influence recipient outcomes after SLT.
We chose 3 months after transplant as the cut-off point to evaluate the short-term outcomes because most of the surgery-related or life-threatening complications occur within 3 months after surgery. One of the severe complications in the early phase after pediatric liver transplant is HAT,[23,24] especially in young and small liver graft recipients.[25,26] Remarkably, none of the recipients in this study developed HAT during our follow-up time. The liver grafts suitable for split were well selected, and the splitting procedure was performed by our specialized team to protect the hepatic artery from unnecessary injuries. Therefore, SLT with pediatric donors does not increase the incidence of HAT in well-selected recipients. The complication with the highest incidence in this study was CMV infection (62.5%). So far, there is no evidence to show the association between small and young liver grafts and CMV infection. The CMV infection in recipients was likely related to the immunosuppressive effect. It is worth noting that the youngest donor for split in this study was 2.7 years old; as far as we know, this is the youngest reported donor in SLT. Both of the recipients had smooth courses of recovery.
In this study, we reported 16 cases of SLT in children who received split liver grafts from deceased pediatric donors <7 years old. Ideal short-term outcomes have been achieved in well-selected donors and recipients. Our study shed light on the potential attempt to push the lower age limit for "split-able" liver grafts. Nevertheless, the long-term follow-up for the recipients is still necessary, and more optimized criteria for selecting "split-able" liver grafts need to be established to further guarantee the safety use of young pediatric donors in SLT in the long run.
We would like to thank the funders of this study: Tianjin Clinical Research Center for Organ Transplantation Project (15ZXLCSY00070), Key Project of Tianjin Health and Family Planning Commission (16KG107), and Tianjin Natural Science Foundation (18JCYBJC44400).
ALT, alanine transaminase; AST, aspartate transaminase; BA, biliary atresia; BC, biliary complication; CLTR, China Liver Transplant Registry; CMV, cytomegalovirus; DBD, donation after brain death; EBV, Epstein-Barr virus; ERL, extended right lobe; GRWR, graft-to-recipient weight ratio; HAT, hepatic artery thrombosis; HBV, hepatitis B virus; ICU, intensive care unit; INR, international normalized ratio; LLS, left lateral segment; PELD, Pediatric End-Stage Liver Disease; PFIC, progressive familial intrahepatic cholestasis; RBC, red blood cell; SLT, split liver transplant; TBIL, total bilirubin.
American Journal of Transplantation. 2020;20(3):817-824. © 2020 Blackwell Publishing