Split liver transplantation in China: Past, present, and future

Split liver transplantation (SLT) is a procedure where an intact donor liver is splitted into two anatomically and functionally independent grafts, which are transplanted to two recipients. SLT can effectively expand the source of donor liver, and has become the predominant surgical solution to the shortage of donor livers after years of exploration and refinement.

History of SLT: The development of SLT procedure was full of twists and turns. Before its development, Bismuth and Houssin reported independent pediatric liver transplantations of liver grafts that had been reduced in size before transplantation in 1984.^[1] Pichlmayr et al^[2] made the first SLT attempt in 1988. In the following year, Bismuth et al^[3] completed a split transplantation of right and left hemilivers, but the two recipients died 20 days and 45 days postoperatively, respectively. Since then, through the joint efforts of experts and scholars, the survival rates of both graft and recipient survival in SLT have been significantly improved. In 1995, the 6-month survival rates for pediatric and adult recipients of SLT and their grafts in Europe are comparable to the cadaveric whole livers from the European Liver Transplant Registry in the same period.^[4] After more than 10 years of development, the SLT technology was basically established in mature transplantation centers in Europe and the United States.

Current status of SLT: With the establishment and improvement of this technology, SLT has now especially reduced the mortality rate of pediatric recipients on the waiting list for liver transplantation without increasing donor risks like living-donor liver transplantation (LDLT). The percentage of adult liver transplant recipients with SLT at the University of California Los Angeles in 2021 was approximately 14% , and the percentage of pediatric recipients was over 40%.^[5] At the beginning of this century, the 3-year survival rates of recipients and grafts of SLT were close to those of whole liver transplantation (WLT) in Italy.^[6] Additionally, patients undergoing SLT and LDLT showed similar outcomes in terms of overall survival, graft survival, or complications.^[7] Overall, the efficacy of SLT is recognizable and has achieved comparable efficacy to WLT and LDLT in both adult and pediatric recipients.

The development of SLT is not evenly widespread. In Italy, the SLT rate is as high as 20% in the north, but only 8% nationwide, and the SLT rate is up to 10% in the United Kingdom, Argentina, and Brazil, and only 6% across Europe. In the United States, while more than 10% of donor livers meet the criteria for splitting, the reality is that only 1–4% of donor livers are split.^[8] SLT in Asia generally started later than in Europe and the United States, and the proportion of LDLT is higher compared to SLT. In South Korea, the proportion of SLT during 2005–2014 was less than 5%, while the proportion of LDLT was as high as 75.1%.^[9] Europe is quite proactive when it comes to SLT. In the United States, donor screening standards are stricter. In China, younger donors are typically selected, and the technology is steadily advancing. Throughout the world, despite its full implementation, SLT application still shows a low proportion and uneven development in various regions.

Innovations in SLT: SLT’s development is also accompanied by continuous innovation. For example, the left and right hemiliver split, derived from the classical split, significantly improved the availability of the transplanted liver. Another example is the in situ splitting technique which maximizes the protection of the quality of the donor liver. Compared to ex vivo SLT, the in situ technique offers several advantages: shorter cold ischemia time, less intraoperative blood loss, and faster recovery for the recipient. The technique of machine perfusion partially mimics the state of perfusion of the donor liver under stable blood flow, and therefore allows for mechanically perfused liver splitting and improves the utilization of marginal donor livers from non-heart-beating donors. In addition, the use of small-sized split donor livers in auxiliary liver transplantation is also promising for the treatment of chronic liver failure. After more than 30 years of development, SLT has achieved tremendous progress in terms of technology and has expanded in terms of indications.

Development of SLT in China: The first SLT was reported in Chinese mainland in 2002. Although that was more than 20 years ago, SLT only gained more room for development after China fully implemented postmortem organ donation for its citizens in 2015. Although SLT started late in China, most of the major transplantation centers in China carry out SLT now. Our center performed the first SLT in July 2014, and has now completed more than 200 cases. By 2022, our transplantation center has the highest number of SLT cases in China. We believe that SLT for biliary atresia in children can achieve clinical outcomes comparable to LDLT.^[10] After years of practice and summarization, a comprehensive theory and key technology system of SLT has been established in our center, including donor–recipient evaluation and matching,^[11] tube splitting and reconstruction,^[12,13] complication monitoring and prevention,^[14] and postoperative follow-up management.

Problems of SLT in China: At present, the main transplantation centers in China have successively performed SLT procedure, but the development of SLT differs in regions and centers, with more procedures performed in Hangzhou, Guangzhou, Chengdu, Tianjin, Beijing, Qingdao, and Shanghai, revealing the reality of unbalanced development and insufficient homogenization at present. The development of SLT requires sufficient time for clinical practice and steady accumulation in order to improve the overall technical level of transplantation centers.

In addition, the incidence of SLT complications still needs to be further controlled. The incidence of complications, such as hepatic artery or portal vein stenosis/thrombosis, hepatic vein stenosis, or outflow tract obstruction, is relatively higher, especially for recipients of left lobe or left lateral lobe donor livers. This is related to the inherent angle between the blood flow into the liver from the left donor liver and the main trunk of the portal vein, or underdeveloped portal vein in low body weight pediatric recipients, or outflow tract obstruction due to torsional deformity during growth and development. These complications may be effectively reduced if the technical protocol is further standardized.

Inadequate sharing of donor liver resources among transplantation centers, coupled with the lack of a policy endorsement encouraging splitting, further contributes to the current state that many transplantation centers choose to forgo splitting in the absence of suitable recipients, resulting in an underutilization of splittable donor liver resources. Similar to some European and American countries, much more donor livers meet the criteria for splitting in China than the ratio of donor livers that are actually split. We need a more complete overall coordination mechanism and distribution policy to narrow this gap. Issues such as these require continued attention and further solutions from experts and practitioners in the field of liver transplantation.

The Path Forward for SLT in China: SLT in China is still in the early stage with unbalanced development in various regions and centers. To expand the donor pool and save more patients waiting for liver transplantation, centers need to be encouraged to carry out this procedure in an orderly manner, while prioritizing the safety of the recipients.

An inter-regional multi-center SLT consortium can address the problem of uneven technology development. For transplantation centers and regions where SLT started late and the technology is not standardized, point-to-point or point-to-region assistance can be provided by larger transplantation centers where SLT was started early. To address the common complications of SLT, technical assistance should be provided to improve graft survival and recipient survival and improve the overall efficacy of SLT in China. Our center took the lead in establishing the South China Split Liver Transplantation Alliance including 25 hospitals in 2020, and was the first to successfully hold a national workshop on SLT, providing a communication platform for centers in the region while exporting our own experience and technology. The alliance has completed nearly 300 SLT cases to date.

Early standardization of the key technology system of SLT in China can circumvent the problem of insufficient homogenization. A universally recognized standard in the industry should be formulated sooner and promoted to all regions and major centers. In addition, major centers should report SLT donor–recipient data in China Liver Transplant Registry (CLTR) in a timely manner, and health authorities or quality control centers should conduct quality control on the major centers and supervise the centers in rational screening of donors and recipients and standardization of surgical procedures. Through years of clinical practice of SLT, our center has led multiple domestic transplantation centers to jointly formulate the “Expert Consensus on Split Liver Transplantation”,^[15] “Expert Consensus on Evaluation of Split Liver Transplantation Donors and Donor Organs”,^[16] and “Chinese Expert Consensus on Vascular Division and Reconstruction in Split Liver Transplantation”,^[17] with every effort to promote the establishment of a standardized technology system of SLT in China.

Today when the number of donor livers available for splitting is much larger than the number of donor livers that are actually split, efforts to increase the proportion of SLT are particularly important and should be doubly safeguarded by policy and communication and collaboration. A pool of recipients in different regions that are eligible for split liver grafts should be established with dynamic updates. A policy should be developed to prioritize splits in the allocation of liver grafts; and allocation of liver segments should be prioritized for allocation for the grafts that meet the criteria of splitting. These measures will increase the SLT ratio and save more lives.

In conclusion, SLT has accounted for more than 8% of liver transplantations completed in China in 2022, which is already a significant increase from only 1.25% in 2016. In response to the current situation of low postmortem organ donation rate of citizens and the prominent shortage of liver supply, SLT plays an extremely important role and has a huge space for development. In future, a great deal of work needs to be done on the establishment and promotion of standardized technologies, exploration and application of innovative techniques, and promotion of policies appropriate to national conditions. With the joint efforts of transplantation colleagues and the support of national policies, China’s SLT will walk a road of high-quality development.

Funding

This work was supported by the National Key R&D Plan (No. 2017YFA0104304), the National Natural Science Foundation of China (No. 81972286), and the Science and Technology Program of Guangdong Province (Nos. 2020B1212060019 and 2017B020209004).

Conflicts of interest

None.