Reflection on 10 problems of clinical xenotransplantation / 器官移植

The shortage of donors restricts the development of organ transplantation. Xenotransplantation might act as an effective approach to resolve this problem. With the advancement of genome editing technologies as well as research and development of novel immunosuppressant, lots of breakthroughs have been achieved in the field of xenotransplantation. Nevertheless, a majority of researches are still in the preclinical stage. Recently, the success of the world's first genetically engineered pig-to-human heart transplantation has greatly inspired researchers. However, clinical xenotransplantation still faces an array of problems, including counteracting rejection, controlling inflammation, regulating coagulation disorder, improving physiological compatibility of xenografts, paying attention to the risk of interspecific infection, optimizing immunosuppressive regimen, screening donor genome editing types, selecting suitable recipients, modifying xenotransplantation guidelines, and awareness of public recognition, etc. In this article, these 10 problems were summarized, aiming to provide reference for promoting the clinical application of xenotransplantation.

New progress on liver transplantation for liver cancer: 2019 ILTS annual collection / 器官移植

The 25th Annual Congress of International Liver Transplantation Society (ILTS) was held from May 15 to 18, 2019 in Toronto, Canada. Focusing on the special topic of liver transplantation for liver cancer, down-staging liver cancer and bridging therapy before liver transplantation, prediction of liver cancer recurrence after liver transplantation, individualized immunosuppressive scheme, prevention and treatment of liver cancer recurrence after liver transplantation were summarized in this article. In addition, the literatures published in recent two years related to the research progress were reviewed.

Tailored long-term immunosuppressive regimen for adult liver transplant recipients with hepatocellular carcinoma

BACKGROUNDS/AIMS: There are few guidelines for tailored immunosuppressive regimens for liver transplantation (LT) recipients with hepatocellular carcinoma (HCC). To establish long-term immunosuppressive regimens suitable for Korean adult LT recipients, we analyzed those that were currently in use at a single high-volume institution. METHODS: This cross-sectional study comprises three parts including review of the immunosuppressive regimens used to manage 2,147 adult LT outpatients, review of LT recipients who were diagnosed of HCC at LT, and review of LT recipients who suffered from HCC recurrence. RESULTS: In 1,000 adult LT recipients who were living more than 5 years with no adverse events, 916 received a calcineurin inhibitor (CNI)-based therapy (CNI only in 520; CNI with mycophenolate mofetil [MMF] in 396) and 84 were receiving an MMF-based therapy (MMF only in 45; MMF with minimal CNI in 39). Tacrolimus was preferred over cyclosporine for both monotherapy and combination therapy along the passage of posttransplant period. There was no difference in selection of immunosuppressants, target blood concentration, and rate of combination therapy between LT recipients with and without HCC, except for the first 1 year. Sirolimus-based regimens were applied in 21 patients who showed HCC recurrence. Sorafenib was often used after conversion to sirolimus. CONCLUSIONS: Tailored immunosuppressive regimen covering the long-term posttransplant period should be established after consideration of individualized patient profiles including HCC.

Liver Transplantation for Advanced Hepatocellular Carcinoma / 대한이식학회지

Hepatocellular carcinoma (HCC) has become an important indication for liver transplantation in Korea. Even though the Milan criteria have been accepted as the gold standard in deceased donor liver transplantation, the acceptable indication for living donor liver transplantation is controversial. This review covers several key issues in liver transplantation for advanced HCC: (1) recent developments and published data on expanded criteria, (2) the role of down-staging, (3) an ethical issue in expanding the criteria in living donor liver transplantation, and (4) post-operative management, including the immunosuppressive regimen and post-transplant adjuvant chemotherapy to improve survival after transplantation for advanced HCC. Biological factors, such as AFP, PIVKA-II, and a PET scan, in addition to tumor size and number, may be helpful in selecting eligible patients for liver transplantation among patients with advanced HCC. Low-level immunosuppression with low exposure of calcineurin inhibitor may reduce HCC recurrence after transplantation.

Effect of Modification of Immunosuppressive Regimen on Renal Allograft Survival Rate in Recipients with Mild Chronic Rejection / 대한이식학회지

Purpose: Concept that modification of immunosuppression can delay the deterioration of graft function and graft failure is the one of strategies for chronic rejection. We analyzed the effect of modification of immunosuppression in 116 recipients with biopsy confirmed mild chronic rejection retrospectively. Methods: Mild chronic rejection was diagnosed by single renal pathologist under the uniformed criteria; mild tubular atrophy & interstitial fibrosis (less than 25%) combined with vascular change such as fibrous intimal thickening. General rules of modification after chronic rejection in our center were (1) strict adjustment of cyclosporine (CsA) dosage around 100~120microgram/L of trough blood level, (2) triple conversion in double therapy recipients (add anti-metabolites; azathioprine or MMF), (3) dose increment of anti-metabolites, (4) maintain of immunosuppression if ongoing immunosuppression is satisfactory to above criteria. Results: After 74.8+/-44.5 months of follow-up, we identified 72 graft failures (62.1%). Overall post-diagnosis graft survival rate were 93.1%, 79.7%, 63.6% and 35.8% in 1, 3, 5 and 10 years respectively. The status of graft function categorizedn by stage of chronic kidney disease (CKD) at diagnosis (CKD 4 or 5 stage), timing of diagnosis (more than post-transplant 3 years) and presence of severe proteinuria (more than 1 g/day of urinary excretion) were significant risk factors affecting the post-diagnosis graft survival rate. In multivariate survival analysis, these factors were confirmed as independent variables affecting post-diagnosis graft survival rate. But modification of immunosuppressive regimen after mild chronic rejection which was classified by modification (yes versus no), type of anti-metabolites (azathioprine versus MMF) and change of immunosuppressive strength (equal versus additional versus incremental) didn't cause the significant difference of post-diagnosis graft survival rate. Conclusion: Though pathologic change is mild, the modification of immunosuppression is not effective to delay graft failure in renal allograft recipient with pathologically established chronic rejection.