ABO-incompatible Pediatric Liver Transplantation Research Articles

Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant.

ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis. A retrospective review of all patients who received an ABOi LT at ourinstitution was performed. Comparisons were made based on era (early: 1997-2008, modern: 2009-2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant. 17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1-28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1. ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.

Progress in perioperative management of ABO-incompatible pediatric liver transplantation

ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.

ABO-incompatible Pediatric Liver Transplantation With Antibody and B-cell Depletion-free Immunosuppressive Protocol in High Consanguinity Communities.

From November 2010 to June 2015, 176 children aged 0.2-to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered. The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5-70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures. ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.

The management and outcomes of ABO-incompatible pediatric liver transplantation: Experience of a single Chinese center

BackgroundTo investigate the safety of using ABO incompatible (ABO-i) liver grafts in pediatric patients under our prophylactic strategies. MethodsA total number of 544 pediatric liver transplantations between January 2013 and December 2017 performed in Organ Transplant Center, Tianjin First Central Hospital were included in this study. The recipients were divided into 3 groups based on the compatibility of donor-recipient blood type matching (ABO-identical group, n = 352, ABO-compatible group, n = 121 and ABO-incompatible group, n = 71). Recipient characteristics, perioperative data, postoperative complications and recipient survival rate were compared. The recipient outcomes between living-related and non-living-related ABO-incompatible liver graft recipients were also compared. ResultsThe median follow-up time in three groups were 3.4 (1.8, 6.4) years, 3.2 (1.8, 6.1) years and 2.8 (1.8, 6.2) years, without statistical difference. The cumulative 1-year and 3-year graft survival rate were 94.3% and 94.0% in ABO-id group, 93.1% and 93.1% in ABO-c group and 97.1% and 97.1% in ABO-i group. The cumulative 1-year and 3-year recipient survival rate were 96.1% and 95.5% in ABO-id group, 94.8% and 94.8% in ABO-c group and 97.1% and 97.1% in ABO-i group, respectively. No significant difference was seen among three groups. The recipient characteristics and perioperative data were similar among three groups. The recipients in ABO-i group showed significantly lower incidence of portal vein stenosis. Apart from that, three groups shared equal incidence of other surgical complications and acute rejection. Among ABO-i liver graft recipients, the cumulative 1-year and 3-year recipient survival rate were 98.2% and 98.2% in living donor liver transplant (LDLT) recipients and 92.9% and 92.9% in deceased donor liver transplant (DDLT) recipients, without significant difference. The incidence of hepatic artery thrombosis was significantly higher in DDLT group compared with LDLT group, while the other complications were similar between two groups. ConclusionOur data revealed that the application of ABO-i liver grafts in pediatric liver transplantation under rational peri-operative management strategy is a safe measure to increase donor availability for pediatric patients in Chinese population. Levels of EvidenceIII

Acute antibody- mediated rejection in ABO-incompatible pediatric liver transplantation: a single center experience in Japan

Introduction: It was reported that patients younger than two years of age were able to accept ABO-incompatible liver transplantation (ABO-I LTx) without any preoperative desensitization treatment. However, evidences of acute antibody-mediated rejection (aAMR) following ABO-I LTx remain limited in pediatric LTx. The aim of this study was to clarify clinical details of aAMR following pediatric ABO-I LTx. Method: We retrospectively analyzed our database of patients who underwent ABO-I LTx in our institute between November 2005 and June 2019. Diagnosis of aAMR was proven by histological findings of dilatation of portal capillaries and positive staining for C4d. Result: There were 103 (18.4%) cases of ABO-I LTx among 560 LTx in our institute. The number of patients under two years of age was 80 (77.7%), who did not receive prophylactic Rituximab as our protocol. The incidence of acute AMR was 6.8% (7 cases) including four patients under two years of age. The youngest was 8-month-old. Two patients over two years of age suffering from aAMR did not receive prophylactic Rituximab due to urgent LTx (acute liver failure). Postoperative anti-donor blood type IgM titers (AdB-IgM) were significantly higher in the cases of aAMR: median titers of aAMR cases was 1:32; that of non aAMR cases was 1:2 (p<0.01). The cutoff values were estimated by a ROC curve as 1:16. On the other hands, preoperative AdB IgM did not show significant difference. As the treatments of aAMR, steroid bolus injection therapy and IVIG were immediately introduced for all patients and additional plasma exchange was performed for three patients, followed by administration of MMF. Although all patients recovered from aAMR, biliary stricture was occurred in a case. Conclusion: It was considered that Rituximab prophylaxis should be extended to the patients under two years of age and we have not to overlook mild elevation of AdB-IgM after pediatric ABO-I LTx.

The Role of Liver Sinusoidal Endothelial Cells in Induction of Carbohydrate Reactive B Cells Tolerance Through the Programmed Death 1/Programmed Death Ligand 1 Pathway.

A spontaneous tolerance of B cells responding to blood group antigens frequently develops in ABO-incompatible pediatric liver transplantation (LT). Liver sinusoidal endothelial cells (LSECs), which exclusively express blood group antigens in the liver, possess a capacity to induce alloantigen-specific tolerance. In this study, we elucidated the role of LSECs in the tolerance induction of blood group antigen-reactive B cells after ABO-incompatible LT using mice that lack galactose-α(1,3)galactose (Gal) epitopes resembling blood group carbohydrate antigens. Using adoptive transfer of LSECs from wild type (WT) C57BL/6J mice to congenic α1,3-galactosyltransferase gene knockout (GalT) mice, we established orthotropic GalT → GalT LSEC chimera mice. Anti-Gal Ab (antibody) production was evaluated after immunization of GalT → GalT LSEC chimera mice with Gal rabbit RBC. Adoptive transfer of LSECs isolated from WT GalT mice via the portal vein resulted in persistent engraftment of Gal LSECs in congenic GalT mouse livers. Only when GalT mice were splenectomized before LSEC inoculation, the GalT → GalT LSEC chimera lost the ability to produce anti-Gal Abs. The administration of blocking monoclonal Abs (mAbs) against programmed death ligand 1 to the splenectomized GalT → GalT LSEC chimera resulted in the recovery of anti-Gal Ab production. These findings suggest that LSECs take a part in tolerization of immature but not mature B cells specifically for Gal. Furthermore, the programmed death 1/programmed death ligand 1 pathway likely plays a crucial role in the mechanisms underlying spontaneous tolerization of B cells responding to ABO-blood group antigens in LT.

Effects of Rituximab On ABO-Incompatible Pediatric Liver Transplantation: A Japanese Multicenter Study.

Effects of Rituximab On ABO-Incompatible Pediatric Liver Transplantation: A Japanese Multicenter Study.

Evidence of Immune Tolerance to Blood Group Antigens in a Case of ABO‐Incompatible Pediatric Liver Transplantation

In a 12-year-old patient with blood group O, who had received a partial liver graft 10 years ago from his father with blood group A, the levels of anti-A-specific antibodies (Abs) were persistently undetectable after the transplantation, while the levels of anti-B-specific Abs gradually increased and attained a plateau. Peripheral blood mononuclear cells (PBMCs) from this patient were engrafted into NOD/SCID mouse in order to investigate the immune response to donor-type blood group antigens. Even after sensitization with blood group-A erythrocytes, no anti-A Abs were detected in the serum samples of the mouse that received PBMCs from the blood group-O recipient of group-A liver allograft, however, immunoglobulins specific for antigens other than the A antigens were produced. Thus, we provide a possible evidence of immune tolerance to blood group antigens in this ABO-incompatible pediatric liver transplantation.

Successful ABO-incompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis

Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.