This report presents the Japanese status of organ procurement from deceased donors for organ transplantation in 2021 during the COVID-19 pandemic in Japan. The Act on Organ Transplantation was established in July, 1997, and amended in June, 2009. After the enforcement of the amended Act on Organ Transplantation in July 2010, the number of brain-dead donors vastly increased. But the total numbers of deceased donors for organ transplantation were almost the same from 2015 to 2018. In 2019 the total number increased to 125. But during the COVID-19 pandemic, the number decreased to 77 in 2020, and to 76 in 2021. In this situation, the numbers of brain-dead donors in 2020 and 2021 were kept almost the same from 2015 to 2018. The Japan Society for Transplantation would like to express its deepest gratitude to those who have expressed their willingness to donate their organs despite the difficult circumstances, to the families who have agreed to donate their organs, and to the medical staff, other related people, and transplant coordinators who have been involved in organ donation in order to respond to their wishes.

A total of 1,773 kidney transplants including 1,648 from living donors, 19 from non-heart-beating donors and 106 from heart-beating donors were performed in 2021 in Japan. The data obtained from the Japanese Renal Transplant Registry are shown and analyzed in this annual report. The characteristics of recipients and donors such as relationships, original diseases, duration of dialysis therapy, blood transfusion, status of viral antigens and antibodies, pretransplant complications, causes of death of deceased donors, ischemic time and histocompatibilities are described. In addition, immunosuppressants used initially and other treatments are analyzed. We also report the results of a follow-up survey for recipients and living donors.

As of December 31, 2021, a total of 10,839 liver transplants had been performed in 70 institutions in Japan. There were 718 deceased donor transplants (715 from heart-beating donors and 3 from non-heart-beating donors) and 10,121 living-donor transplants. The annual total of liver transplants in 2021 was 421. Deceased-donor transplants decreased to 63 in 2020 and 60 in 2021 from 88 in 2019, probably due to the COVID-19 pandemic. The most frequent indication was cholestatic disease, followed by hepatocellular disease and neoplastic disease. As for hepatocellular disease in 2021, alcoholic cirrhosis and non-alcoholic steatohepatitis were the most common. Patient survival following transplantation from heart-beating donors (715 transplants: 1-year 88.9%, 3-year 86.3%, 5-year 82.9%, 10-year 76.1%, 15-year 68.3%, 20-year 57.8%) was similar to that from living-donors (10,121 transplants: 1-year 85.7%, 3-year 81.9%, 5-year 79.4%, 10-year 74.4%, 15-year 69.7%, 20-year 65.2%, 25-year 62.3%, 30-year 58.8%). Graft survival was very much the same as patient survival (heart-beating donor: 1-year 88.5%, 3-year 85.9%, 5-year 82.5%, 10-year 75.7%, 15-year 67.9%, 20-year 57.5%，living-donor: 1-year 85.1%, 3-year 80.9%, 5-year 78.3%, 10-year 72.7%, 15-year 67.6%, 20-year 62.6%, 25-year 59.5%, 30-year 55.4%). Survival data are reported according to age and sex of recipient, indication, graft type, age and sex of donor, ABO-compatibility, and other factors. Cause of death of living liver donors is also reported.

Since the Organ Transplantation Act was passed in October 1997, a total of 625 heart transplantations (HTx) have been performed in Japan as of December, 2021. Of those, 556 HTx were performed after activation of a revised Transplant Act, and 84 were performed in 2019, which fell to 56 due to the COVID-19 pandemic in 2021. Most recipients had dilated cardiomyopathy; and the waiting condition of all patients was status 1 at HTx. The mean waiting time as status 1 continuously increased to 1,815 days in 2021 from 892 days in 2014 in adults. After approval of the use of an implantable continuous flow ventricular assist device (cf-LVAD) for bridge-to-transplant (BTT) in 2011, BTT, especially using cf-LVAD, increased. In 2021, 51 of 56 adult cases were supported by several types of cf-LVADs. Sixty children underwent HTx and 46 (77%) of them were BTT cases (8 in Nipro VAD, 20 in EXCOR VAD, 9 in Jarvik 2000 and 9 in other cf-VADs). Most patients underwent a modified bicaval method of operation with Celsior for cardiac preservation, and all recipients were administered triple therapy with calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and a steroid as an initial immunosuppressive regimen. Patient survival at 5, 10 and 20 years was 93.3%, 89.4% and 77.5%, respectively, which is superior to that of the international registry. This surveillance documented that the results of HTx in Japan were excellent despite a severe shortage of donors and long waiting times with LVAD as BTT.

【Objective】 To scrutinize the status of lung transplantation in Japan, the Japanese Society of Lung and Heart-Lung Transplantation started to collect and present registry data in 2005. This is the 18th official registry report of Japanese lung transplantation.

【Design and Methods】 The data on cadaveric lung transplantation and living-donor lung transplantation performed by the end of 2021 were registered in the database and analyzed regarding the number of transplants, recipient survival rates, recipient functional and working statuses, and causes of death after transplantations. Survival rates were calculated by the Kaplan-Meier method.

【Results】 A total of 658 cadaveric lung transplantation (350 single, 308 bilateral), 270 living-donor lung transplantation, and 3 heart-lung transplantation procedures were performed by the end of 2021. The number of cadaveric lung transplants reached the record high of 93 in 2021. Five-year and 10-year survival rates of cadaveric lung transplantations were 73.7% and 61.4%, which were superior to those in the international registry. Five-year and 10-year survival rates of living-donor transplantations were similar to those of cadaveric lung transplantation with 73.8% and 62.5%. The 3 recipients of heart-lung transplantation are all alive. The functional status of approximately 80% of recipients was restored to the mMRC scale of grade 0 or 1 after cadaveric and living-donor lung transplantations. The mMRC of the 3 heart-lung transplant recipients was grade 0. Infection has been the leading cause of death after lung transplantation. The number of deaths from chronic lung allograft dysfunction, malignancy and post-transplantation lymphoproliferative disease have been increasing in recent years.

【Conclusion】 The outcomes of Japanese lung transplantation are so far satisfactory. The modified Japanese transplantation law has been enforced since July 2010, and an increase in the number of cadaveric organ transplantations was achieved after that. In 2020, the number of lung transplants decreased due to the influence of the COVID-19 pandemic; however, in 2021, the number recovered and reached a record high. The Japanese Society of Lung and Heart-Lung Transplantation will continue to present annual reports of Japanese lung transplantations.

A total of 488 cases of pancreas transplantation from deceased and living-related donors were performed in 21 institutions in Japan between April 2000 and the end of 2021. The following donor- and recipient-related factors were analyzed: age and gender of donor and recipient, cause of death, history of diabetes and hemodialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and posttransplant survival rates of patient and graft. Based on the analyses, the current status of pancreas transplantation in Japan was described. The patient survival after the transplantation was 95.8%, 94.5% and 92.5% at 1, 3, and 5 years, respectively. The pancreas graft survival in cases with simultaneous pancreas and kidney transplantation (SPK) was 87.5%, 84.8%, and 82.8% at 1, 3, and 5 years, respectively. The pancreas graft survival in cases with pancreas after kidney transplantation (PAK) (82.4%, 67.4%, and 54.9% at 1, 3, and 5 years, respectively) and pancreas transplantation alone (PTA) (68.4%, 44.9%, and 32.1% at 1, 3, and 5 years) was significantly poorer than for SPK. The main cause of pancreas graft loss was graft thrombus in SPK cases, while it was chronic rejection in PAK and PTA cases. In conclusion, we demonstrated the current status of pancreas transplantation in Japan. While the posttransplant outcome was favorable, it is necessary to overcome graft thrombus in SPK cases and chronic rejection in PAK and PTA cases for improving the posttransplant outcomes.

Following the first clinical islet transplantation procedure in 2004 and the initial era of performing islet transplantation as a single-center clinical trial, a multicenter clinical trial of islet transplantation with the goal of achieving coverage by national health insurance was started in 2012. Improvement of islet transplantation outcomes was achieved using anti-thymocyte globulin, and islet transplantation finally obtained coverage by Japanese national health insurance in 2020, marking the advent of the third era of clinical islet transplantation. Unfortunately, there were no cases of islet transplantation in 2020, as the start of the COVID-19 pandemic resulted in a decrease in donor information for islet transplantation. However, in 2021, two clinical islet transplants were performed. We herein report the impact of the COVID-19 pandemic on islet transplantation in Japan, which started at almost the same time as the introduction of national health insurance coverage for islet transplantation, and describe the two cases of islet transplantation performed in 2021.

Thirty-five intestinal transplants were performed since 1996 in 6 institutions. There were 24 deceased donor and 13 living donor transplants. Primary causes of intestinal transplants were short gut syndrome (n=17), intestinal mobility function disorder (n=15), others (n=1) and re- transplantation (n=4). One-year patient survival was 91%, and 10-year patient survival was 59%. They were excellent results for a standard therapeutic option for intestinal failure if patients failed to maintain total parental nutrition.

Hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for a wide range of otherwise fatal hematologic disorders, and the number of HSCTs has continued to increase over the last 30 years; more than 5,000 allogeneic and autologous HSCTs have been performed annually in recent years. A constant increase of allogeneic HSCTs for older (aged over 50) patients, and an increase in the variety of donor/stem cell sources such as cord blood from unrelated donors have led to this constant increase of HSCT in Japan. The transplant survival outcome also continues to improve and the assets for the improvement include better supportive care, innovative transplant approaches, and the considerable contribution of a well-established transplant outcome registry to a variety of clinical studies.

The case is that of a 12-year-old girl. Kasai’s procedure was performed for biliary atresia on the 29th day of life. Liver failure gradually progressed, and she was referred to our hospital for living-donor liver transplantation (LDLT). She was genetically diagnosed with Rett syndrome at the age of 5, and due to the decline in motor function and language function associated with Rett syndrome, she was able to express emotion but she only spoke babblingly and could hardly communicate, and thought she was able to stand and walk, she was unstable. The movement of putting a fist in the mouth and bruxism, which are peculiar to patients with Rett syndrome, were frequently observed. Although she had autism due to Rett syndrome, the neurological and life prognosis of Rett syndrome was predicted to be good, and her family had a positive desire for liver transplantation and was available to cooperate in postoperative management. Based on the above, we judged that the case was suitable for LDLT and performed LDLT using a left lobe graft with caudate lobe with the father of the patient as a donor. Although Rett syndrome is a refractory mental and nervous system systemic progressive disease, the prognosis of liver cirrhosis is significantly worse than that of Rett syndrome in this case. Liver transplantation was acceptable, after balancing the potential risks and benefits.