How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach

BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.

Outcome of split liver transplantation vs living donor liver transplantation:A systematic review and meta-analysis

BACKGROUND The outcomes of liver transplantation(LT)from different grafts have been studied individually and in combination,but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT(DD-SLT)and living donor LT(LDLT).AIM To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.METHODS This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.The following databases were searched for articles comparing outcomes of DD-SLT and LDLT:PubMed;Google Scholar;Embase;Cochrane Central Register of Controlled Trials;the Cochrane Database of Systematic Reviews;and Reference Citation Analysis(https://www.referencecitationanalysis.com/).The search terms used were:“liver transplantation;”“liver transplant;”“split liver transplant;”“living donor liver transplant;”“partial liver transplant;”“partial liver graft;”“ex vivo splitting;”and“in vivo splitting.”RESULTS Ten studies were included for the data synthesis and meta-analysis.There were a total of 4836 patients.The overall survival rate at 1 year,3 years and 5 years was superior in patients that received LDLT compared to DD-SLT.At 1 year,the hazard ratios was 1.44(95%confidence interval:1.16-1.78;P=0.001).The graft survival rate at 3 years and 5 years was superior in the LDLT group(3 year hazard ratio:1.28;95%confidence interval:1.01-1.63;P=0.04).CONCLUSION This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.

Progress of mechanical perfusion in split liver transplantation

Split liver transplantation is an essential means which expand the donor pool currently and the two livers obtained after splitting are marginal donor livers.The adoption of Static Cold Storage during allocation and preservation leads to a higher cold ischemia time,thus increasing the occurrence of related postoperative complications,which limits the further development of split-liver transplantation.Mechanical perfusion as a complement to split liver transplantation can minimize the damage to the marginal donor liver during preservation and reduce the occurrence of ischemia-reperfusion.At present,mechanical perfusion has achieved better efficacy in other types of marginal donor liver transplantation such as DCD,elderly donor liver,fatty liver,and so on.In recent years,mechanical perfusion has also shown great potential for application in split-liver transplantation,and limited clinical studies have shown outstanding therapeutic effects.Therefore,this paper will summarize the research progress and mechanisms related to the application of mechanical perfusion in split liver transplantation in order to promote the application of mechanical perfusion in split liver transplantation and reduce the damage of the organ during preservation.

Using on-site liver 3-D reconstruction and volumetric calculations in split liver transplantation

BACKGROUND： Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. METHODS： Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. RESULTS： The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g （930-1458 g） for the extended right lobe donors and 312 g （222-396 g） for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts,respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight.CONCLUSIONS： On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.

Topological approach of liver segmentation based on 3D visualization technology in surgical planning for split liver transplantation

BACKGROUND Split liver transplantation(SLT)is a complex procedure.The left-lateral and right tri-segment splits are the most common surgical approaches and are based on the Couinaud liver segmentation theory.Notably,the liver surface following right trisegment splits may exhibit different degrees of ischemic changes related to the destruction of the local portal vein blood flow topology.There is currently no consensus on preoperative evaluation and predictive strategy for hepatic segmental necrosis after SLT.AIM To investigate the application of the topological approach in liver segmentation based on 3D visualization technology in the surgical planning of SLT.METHODS Clinical data of 10 recipients and 5 donors who underwent SLT at Shenzhen Third People’s Hospital from January 2020 to January 2021 were retrospectively analyzed.Before surgery,all the donors were subjected to 3D modeling and evaluation.Based on the 3D-reconstructed models,the liver splitting procedure was simulated using the liver segmentation system described by Couinaud and a blood flow topology liver segmentation(BFTLS)method.In addition,the volume of the liver was also quantified.Statistical indexes mainly included the hepatic vasculature and expected volume of split grafts evaluated by 3D models,the actual liver volume,and the ischemia state of the hepatic segments during the actual surgery.RESULTS Among the 5 cases of split liver surgery,the liver was split into a left-lateral segment and right trisegment in 4 cases,while 1 case was split using the left and right half liver splitting.All operations were successfully implemented according to the preoperative plan.According to Couinaud liver segmentation system and BFTLS methods,the volume of the left lateral segment was 359.00±101.57 mL and 367.75±99.73 mL,respectively,while that measured during the actual surgery was 397.50±37.97 mL.The volume of segment IV(the portion of ischemic liver lobes)allocated to the right tri-segment was 136.31±86.10 mL,as determined using the topological approach to liver segmentation.However,during the actual surgical intervention,ischemia of the right tri-segment section was observed in 4 cases,including 1 case of necrosis and bile leakage,with an ischemic liver volume of 238.7 mL.CONCLUSION 3D visualization technology can guide the preoperative planning of SLT and improve accuracy during the intervention.The simulated operation based on 3D visualization of blood flow topology may be useful to predict the degree of ischemia in the liver segment and provide a reference for determining whether the ischemic liver tissue should be removed during the surgery.

Role of basic studies in expanding the donor pool for liver transplantation

BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease, but a huge gap remains between the number of people who need a liver transplant and the number of organs available. In order to maximize donor organ access for adult and pediatric recipients, novel surgical and liver replacement procedures have evolved. Newer surgical techniques include split cadaveric liver transplantation and living donor liver transplantation (LDLT). With marginal and abnormal donor livers, despite tremendous advances in surgical technology, individual surgical procedure can not be completely brought into play unless effective measurements and basal studies are undertaken. DATA SOURCES: A literature search of MEDLINE and the Web of Science database using 'liver transplantation' and 'expanding donor pool' was conducted and research articles were reviewed. RESULTS: Therapies directed toward scavenging O(2-), inhibiting nicotinamide adenine dinucleotide phosphate oxidase, and/or immuno-neutralizing tumor necrosis factor-alpha may prove useful in limiting the liver injury induced by surgical procedures such as split liver transplantation or LDLT. Improved donor organ perfusion and preservation methods, modulation of inflammatory cytokines, energy status enhancement, microcirculation amelioration, and antioxidant usage can improve non-heart beating donor liver transplantation. Effective measures have been taken to improve the local conditions of donor cells with steatosis, including usage of fat-derived hormone and inflammatory mediators, ischemic preconditioning, depletion of Kupffer cells, and cytokine antibody and gene therapy. Double-filtration plasmapheresis can effectively reduce HCV viremia and prevent HCV recurrence in patient with high HCV RNA levels after LDLT. CONCLUSIONS: Shortage of grafts and poor function of marginal and abnormal donor grafts put many patients at risk of death in waiting for liver transplantation. Advances in surgical technology, combined with improvement and breakthroughs in basic studies hold a promise in expanding the liver donor pool.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Partial liver transplantation

Partial liver transplantation,including reducedsize liver transplantation,split liver transplantation,and living donor liver transplantation,has been developed with several innovative techniques because of donor shortage.Reduced-size liver transplantation is based on Couinaud’s anatomical classification,benefiting children and small adult recipients but failing to relieve the overall donor shortage.Split liver transplantation provides chances to two or even more recipients when only one liver graft is available.The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality.The first and most important issue involving living donor liver transplantation is donor safety.Before surgery,a series of donor evaluations—including anatomical,liver volume,and liver function evaluations—is indispensable,followed by ethnic agreement.At different recipient conditions,auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation,which employ piggyback techniques,are good alternatives.Partial liver transplantation enriches the practice and knowledge of the transplant society.

Chinese expert consensus on evaluation of donor and donor liver for split liver transplantation

With the advent of the era of organ donation after citizen's death,split liver transplantation(SLT)can effectively increase the supply of donor livers and shorten the transplantation wait time for patients,especially pediatric recipients.In recent years,SLT has been performed to varying degrees in many transplant centers in China,and varying levels of efficacy have been achieved.The quality of donors and donor livers for SLT is an important factor affecting the outcome of the surgery.At this stage,it is necessary to reach a consensus on the evaluation of SLT donor and liver donor that is suitable for the conditions in China by combining the well-established experience of the international community with advanced transplantation technology.This approach will aid in enhancing the efficacy of SLT.Based on the experience of experts,a consensus on the evaluation of donors and donor livers for SLT has been formulated in this study,which focuses on evaluation of donors and donor livers,evaluating the functional and anatomical aspects of the donor liver and donorerecipient matching.