First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China: 5-year Experience at a High-volume Donor and Recipient Liver Transplant Center.

CHINA ARRIVING IN THE INTERNATIONAL TRANSPLANT COMMUNITY Organ transplantation in China has a long history of success and challenges. Since the 1960s, animal experiments have been performed in organ transplantation, providing the foundation for successful clinical procedures. In 1972, our center performed the first living donor kidney transplantation in China. Since then, kidney and liver transplant programs have evolved. By the beginning of the 21st century, organ transplantation had advanced, and clinical liver transplants have been performed successfully at the First Affiliated Hospital of Sun Yat-sen University.1 Organ shortage has been a prominent feature at our institution as it has been around the world. Starting in the early 1980s, many organs had been procured from inmates on death rows. This unethical approach has been rightfully criticized by the worldwide community. As a consequence, the source of organs for transplants has solely been replaced by voluntary donations from Chinese citizens since January 1, 2015. After a decade of arduous work, China has completed the transition from the use of organs from death row inmates to voluntary donations from citizens. In 2006, the Medical Secretary of the Ministry of Health issued The Interim Regulations on the Administration of Clinical Application of Human Organ Transplantation Technology, representing the first legal framework on organ transplantation in China provided by the health administration. In March 2007, the State Council announced The Regulations on Human Organ Transplantation as an ethically accepted legal framework of organ transplantation in China including the sources of organ donation in addition to the rights and protection of citizens to donate. After 3 years of laborious efforts, the legal framework was completed. In addition, scientific standards and procedures for determining the 3 types of organ donation deaths were standardized in China and included donor after brain death (DBD, C-I), donor after circulatory death (DCD, C-II), and donor after brain and circulatory death (DBCD, C-III). Moreover, policies and methods for humanitarian aid to donor families were established. Those policies follow WHO guidelines while recognizing specific aspects of the Chinese culture. The State Ministry of Health and the Red Cross Society of China launched a pilot project on organ donation after the death of citizens in 2010 and established the China Organ Donation Committee. The principle of this pilot project was to learn from the experiences and standards in developed countries while recognizing national conditions and the social reality in China aiming to build an ethical and effective scientific organ donation and transplantation system.2 In August 2013, China’s Health and Family Planning Commission issued The Regulations on the Administration of Human Donor Organ Procurement and Allocation (for Trial Implementation), regulating organ donation and ensuring the implementation of worldwide accepted ethical standards in organ donation in China. This approach demands strict compliance with the 3 Chinese definitions for donation (DBD, DCD, and DBCD) and procedures for voluntary organ donation after the death of a citizen, the establishment of an effective organ procurement organization, and a team of professional coordinators and social workers involved in human organ donation. Moreover, these regulations demand the strict use of the China Organ Transplant Response System to implement allocation. Since January 1, 2015, the China Human Organ Donation and Transplantation Committee has announced that voluntary organ donation by citizens is the only legal source of deceased donor organ transplantation in China. After tireless efforts, a Global Organ Donation and Transplantation Conference held on October 17, 2015, unanimously passed a resolution that China officially join the international organ transplantation family, ending the long history of exclusion and isolation of the Chinese transplantation community. The entry of China into the international organ transplant community ushered an unprecedented advancement of transplantation in China, facilitating entry into a new historical stage of sustainable progress: From 2010 to the end of 2019, a total of >27 000 deceased Chinese citizens organ donors have been reported, and the number of procured solid organ transplants exceeded 78 000. A total of 19 449 organ transplants have been performed nationwide in 2019, including 6170 liver transplants and 12 124 kidney transplants.3 The number of organs donated annually ranks among the highest in the world, aiding countless patients in urgent need of transplantation for terminal diseases. ORGAN TRANSPLANTATION AT THE FIRST AFFILIATED HOSPITAL OF SUN YAT-SEN UNIVERSITY The First Affiliated Hospital of Sun Yat-sen University in Guangzhou is one of the most recognized academic medical centers in China and the birthplace of organ transplantation in the country, having performed the first successful kidney transplant in China, the first combined liver and kidney transplantation, and the first multiple organ transplantation in Asia. In 2017, the world’s first ischemia-free liver transplantation (LT) was successfully performed at our institution. In 2021, we also performed the world’s first ischemia-free heart transplant. During the recent 5 years, >1100 livers have been donated, and >1000 livers have been successfully transplanted in our center. The advancement of organ transplantation at our center can be envisioned as a microcosm representing the progress in transplantation observed in the entire country. About 48.0% of our deceased donors are imported into the Guangdong Province, where our center is located (Figure 1A). At the same time, >70% of all organs procured at our institution have been transplanted in our center. Those numbers suggest that many patients transplanted at our center live outside of our province.FIGURE 1.: A, Native place distribution of donors. Generally, 63.3% (459/882) of the donors resided within Guangdong Province. The city of Maoming (229, 25.9%) was the top area based on the number of donors. B, Numbers of donations every year. Compared with 2015, the number of donations increased by 51.4%, 83.1%, and 85.6% in 2016, 2017, and 2018, respectively. In total, 71.9% (792/1101) of donated organs were maintained and procured in our center, and 28.1% (309/1101) were imported grafts obtained from other centers and then transplanted in our center.LT More than 50% of our liver transplant recipients had a primary diagnosis of liver cancer followed by posthepatitic cirrhosis, and the vast majority (>90%) was 15 to 64 years of age. The prevalence of hepatitis B virus (HBV) infection in the general population of China remains high, and >90% of patients with HBV infections were >20 years old. HBV infections also represent the main cause of posthepatic cirrhosis and liver cancer (Figure 1). Most organs at our center have been recovered from DBDs or DCDs with comparable short- and long-term outcomes. In addition, ~3% of our donors had a diagnosis of brain and circulatory death (DBCD). Procurements from DBCDs are controlled, impacting the quality of donated organs. However, initial hepatocellular injury during the recovery and preservation process is considered a common problem when using organs from DBCDs. In comparing short- and long-term survival among these 3 types, we were able to document comparable transplant outcomes (Figures 2 and 3).FIGURE 2.: Recipient demographic characteristics. A, Recipient distribution in China. Most of the recipients were from Guangdong Province (n = 696, 67.0%). B, Recipients’ gender and age composition and surgical methods. C, Recipients’ pretransplant diagnosis each year. Cancer (52.6%) was the most common diagnosis, followed by posthepatitic cirrhosis (21.7%) D, Recipients’ perioperative conditions. The occurrence rates of EAD and PNF in 2015 were 49.0% and 2.8%, respectively, with rates declining annually. By 2020, the occurrence rates of EAD and PNF had decreased to 23% and 1.2%, respectively. Likewise, 30- and 90-d mortality rates decreased with 30- and 90-d mortality rates of 1.2 in 2020. EAD, early allograft dysfunction; PNF, primary nonfunction.FIGURE 3.: Survival analysis. A, Overall survival. B, Comparison between donor with/without HBV infection. C, Comparison between donor with/without macrovesicular steatosis (>20%). D, Comparison between donor with/without hypernatremia. E, Comparison between different donor types. F, Comparison between recipients with different diagnosis. DBCD, donor after brain and circulatory death; DBD, donor after brain death; DCD, donor after circulatory death; HBV, hepatitis B virus.The definition of extended criteria liver donors (ECDs) is usually based on advanced age, macrovesicular steatosis, DCD, hypernatremia (>165 mmol/L), hyperbilirubinemia (>51.3 mmol/L), anoxia, cerebrovascular accident, and prolonged cold ischemia times.4 Our center also utilizes donors with steatosis and infectious diseases (HBV) and hypernatremia. Outcomes of LT from ECDs suggest that the HBsAg-positive liver grafts do not increase postoperative morbidity and mortality. Moreover, with short cold ischemia time, outcomes after transplantation of steatotic liver and nonsteatotic livers have been comparable. We also observed that the level of donor sodium before organ procurement did not negatively impact early outcomes following in both adult and pediatric liver transplant recipients. The prognosis after LT varies among recipients based on the primary diagnosis. The 5-y survival rate after LT for hepatocellular carcinoma in the current studies varied from 60% to 85%. The 5-y survival rates after LT for benign diseases including posthepatic cirrhosis have been higher, varying from 74% to 88%. Recurrence of primary disease and organ shortage are the main problems currently limiting LT. Therefore, identifying approaches preventing recurrence of the original disease and expanding the pool of available liver grafts are of great significance to improve survival after LT. Outcomes in our center showed the best prognosis after LT for posthepatic cirrhosis and the lowest survival rate for patients with malignancies (Figure 3). Milan and UCSF criteria were considered the standard for the selection of HCC patients at our center. However, many patients in China undergo liver resections if the cancer diagnosis has been made earlier. LT is thus frequently only considered when other treatments have been ineffective or after further tumor progression. Based on very recent data, liver transplants in patients beyond the Milan criteria may have improved outcomes when implementing bridging therapies, including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. Our previous study suggested that radiofrequency will be beneficial in patients with circulating tumor cells.5 Expanding the liver graft pool and utilizing less than optimal grafts come with the risk of early allograft dysfunction and primary nonfunction. Innovative techniques and strategies are needed to protect these high-risk grafts from the deleterious effects of conventional preservation and ischemia-reperfusion injury (IRI). Our center introduced a new technique termed ischemia-free LT, which completely avoids IRI. Our initial experience has shown that this technique has significant advantages over preservation methods in restoring allograft function and reducing the incidence of complications.6 Our first-in-human trial showed that ischemia-free LT therefore provides a novel approach improving outcomes and thus allows the successful utilization of ECD livers.7 For some livers from DCDs, we have also designed a novel continuous normothermic machine perfusion without recooling, thus avoiding a second IRI.8 Early results have shown that this technique is efficacious and safe for LT with ECD livers.9 In conclusion, we present our experience of organ donations and transplantations in our center over the past 5 years. Our patients reside nationwide, emphasizing the leading role of our center in China. Based on numerous efforts, including organ reconditioning, expansion of donor organ pool, and novel transplant technics, survival after LT has improved at our center. Our novel approaches of organ preservation support the utilization of less than optimal organs, thus addressing the pressing problem of organ shortage.