ABO-compatible Liver Transplantation Research Articles

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

ABO-Incompatible Liver Transplantation under the Desensitization Protocol with Rituximab: Effect on Biliary Microbiota and Metabolites.

Background: ABO-incompatible liver transplantation (ABOi LT) under the desensitization protocol with rituximab had excellent survival outcomes comparable to those of ABO-compatible liver transplantation (ABOc LT). In this work, we explored the effect of ABOi LT on recipients from the perspective of biliary microbiota and metabonomics. Methods: Liver transplant (LT) recipients treated at our center were enrolled in the study. In total, 6 ABOi LT recipients and 12 ABOc LT recipients were enrolled, and we collected their bile five times (during LT and at 2 days, 1 week, 2 weeks and 1 month after LT). The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. Results: We obtained 90 bile samples. Whether in group ABOi LT or ABOc LT, the most common phyla in all of the samples were Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The most common genera were Lactobacillus, Weissella, Klebsiella, Pantoea and Lactococcus. There was no significant difference in the diversity between the two groups at 1 week, 2 weeks and 1 month after LT. However, the biggest disparities between the ABOi LT recipients and ABOc LT recipients were observed 2 days after LT, including increased biodiversity with a higher ACE, Chao1, OBS and Shannon index (p < 0.05), and more Staphylococcus in ABOi LT and binary−Jaccard dissimilarity, which indicated varying β-diversity (p = 0.046). These differences were not observed at 1 week, 2 weeks and 1 month after LT. The principal coordinate analysis (PCoA) revealed that the composition of the bile microbiota did not change significantly within 1 month after LT by longitudinal comparison. In an analysis of the bile components, the metabolites were not significantly different every time. However, four enrichment KEGG pathways were observed among the groups. Conclusion: These findings suggest that ABOi LT under the desensitization protocol with rituximab did not significantly affect the biliary microbiota and metabolites of recipients.

Lactic Acidosis, Hypoglycemia, and Eosinophilia: Novel Markers of Antibody-Mediated Rejection Causing Graft Ischemia.

Historically, minimal significance has been given to the humoral immune response after liver transplantation and, despite antibodies against HLA antigens being present in 10-20% of patients awaiting transplant, the incidence of antibody mediated rejection (AMR) after ABO compatible (ABO-C) liver transplantation is low (1).Donor Specific Antibodies (DSA) can lead to early graft loss (2), but most patients awaiting liver transplant are not screened for HLA sensitisation and serum DSA measurement are only undertaken if AMR is suspected. We describe two cases of AMR occurring within one week of ABO-C liver transplantation with previously unreported biochemical and histological characteristics.

Comparison of clinical outcomes between ABO-incompatible and ABO-compatible pediatric liver transplantation: a systematic literature review and meta-analysis.

ABO-incompatible (ABO-i) liver transplantation (LT) is a life-saving method for pediatric patients in emergency situations that has the potential to expand the pool of liver donors. However, the risks of ABO-i compared to ABO-compatible (ABO-c) LT are unclear. To address this clinical uncertainty, we conducted a systematic review and meta-analysis to compare clinical outcomes between ABO-i and ABO-c LT in pediatric patients. A systematic search for studies comparing outcomes between ABO-i and ABO-c LT was performed in the MEDLINE (PubMed), EMBASE, and Cochrane Library databases through May 2020. Outcomes evaluated included graft survival rate, patient survival rate, rejection, infection, biliary complications, and vascular complications. Quality of evidence was assessed using the Newcastle-Ottawa scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3. A total of 12 studies involving 7461 patients were included in the review. Meta-analysis of these studies showed significantly lower 1year, 3year, and 5year graft survival rates for ABO-i vs. ABO-c LT (1year: OR = 0.46, 95% CI 0.35-0.59, P < 0.00001; 3years: OR = 0.47, 95% CI 0.36-0.63, P < 0.00001; 5year: OR = 0.48, 95% CI 0.37-0.63, P < 0.00001) as well as significantly lower 1year, 3year, 5year, and 10year patient survival rates for ABO-i vs. ABO-c (1year: OR = 0.34, 95% CI 0.24-0.49, P < 0.00001; 3years: OR = 0.24, 95% CI 0.14-0.40, P < 0.00001; 5years: OR = 0.47, 95% CI 0.35-0.64, P < 0.00001; 10years: OR = 0.59, 95% CI 0.38-0.90, P = 0.02). No significant differences were observed between the groups in incidence of cytomegalovirus infection, acute cellular rejection, acute rejection, biliary complications, or hepatic artery thrombosis. Our systematic review and meta-analysis showed consistently lower patient survival and graft survival in pediatric ABO-i LT compared to ABO-c LT. However, ABO-i LT is still a life-saving emergency option for pediatric patients waiting for a suitable liver source.

IMPACT OF THE BASELINE ANTI-A/B IGG TITER ON THE CLINICAL OUTCOME IN ABO-INCOMPATIBLE LIVER TRANSPLANTATION

Backgrounds: The use of ABO incompatible (ABOi) living donors is an attractive solution for expanding the liver donor pool. We investigated the impact of the baseline anti-A/B IgG titer on the transplant outcomes in ABOi liver transplantation (LT). Methods: We analyzed 394 adult patients who underwent living donor LT (303 ABO compatible LT and 91 ABOi LT) between 2012 and 2018. ABOi LT patients were categorized by baseline IgG titer: low IgG titer (≤ 1:64, n=51) versus high IgG titer (≥ 1:128, n=40). All ABOi LT patients received desensitization therapy including rituximab and plasmapheresis. Results: Patients with high IgG titer experienced antibody rebound (≥ 1:64) more frequently than those with low IgG titer during the first month after LT (35.0% vs. 15.7%, P=0.033). Patient survival rates for ABO compatible, low IgG titer, and high IgG titer were 85.0%, 91.5%, and 74.4%, respectively, at 3 years post-transplantation (P=0.006). High IgG titer (HR, 2.76; 95% CI, 1.39-5.48; P=0.004) and MELD score of >20 (HR, 2.32; 95% CI, 1.22-4.41; P=0.010) were independent risk factors for mortality. Infection was the leading causes of death in all groups, but the proportion was significantly higher in high IgG titer group than in other groups (81.8% vs. 30.8% vs. 33.3%). Conclusion: Patients with high IgG titer (≥ 1:128) are associated with a higher risk of death after ABOi LT than those with low IgG titer (≤ 1:64). Thus, ABOi LT patients with high IgG titer should be managed with great care.

Influence of Transfusion on the Risk of Acute Kidney Injury: ABO-Compatible versus ABO-Incompatible Liver Transplantation.

ABO-incompatible liver transplantation (ABO-i LT) is associated with a higher risk of acute kidney injury (AKI) compared to ABO-compatible liver transplantation (ABO-c LT). We compared the risk of AKI associated with transfusion between ABO-c and ABO-i living donor liver transplantation (LDLT). In 885 cases of LDLT, we used a propensity score analysis to match patients who underwent ABO-c (n = 766) and ABO-i (n = 119) LDLT. Baseline medical status, laboratory findings, and surgical- and anesthesia-related parameters were used as contributors for propensity score matching. AKI was defined according to the “Kidney Disease Improving Global Outcomes” criteria. After 1:2 propensity score matching, a conditional logistic regression analysis was performed to evaluate the relationship between the intraoperative transfusion of packed red blood cells (pRBCs) and fresh frozen plasma (FFP) on the risk of AKI. The incidence of AKI was higher in ABO-i LT than in ABO-c LT before and after matching (after matching, 65.8% in ABO-i vs 39.7% in ABO-c, p < 0.001). The incidence of AKI increased in direct proportion to the amount of transfusion, and this increase was more pronounced in ABO-i LT. The risk of pRBC transfusion for AKI was greater in ABO-i LT (multivariable adjusted odds ratio (OR) 1.32 per unit) than in ABO-c LT (OR 1.11 per unit). The risk of FFP transfusion was even greater in ABO-i LT (OR 1.44 per unit) than in ABO-c LT (OR 1.07 per unit). In conclusion, the association between transfusion and risk of AKI was stronger in patients with ABO-i LT than with ABO-c LT. Interventions to reduce perioperative transfusions may attenuate the risk of AKI in patients with ABO-i LT.

Passenger Lymphocyte Syndrome After Pediatric Liver Transplantation

Passenger lymphocyte syndrome (PLS) is a less known etiology of acute onset anemia following ABO-compatible (ABO-c) liver transplantation (LT). Available literature on PLS after pediatric LT is limited. Therefore, we evaluated the prevalence, clinical course, and risk factors of PLS in children following ABO-c LT. A single-center retrospective review of all children who underwent LT between 2000 and 2017 was performed. PLS was defined as a drop-in hemoglobin >20 g/L within 30 days of LT, with positive direct antiglobulin test and 1 laboratory test confirming hemolysis. Chi square and student t tests compared variables between subjects with and without PLS. Amongst 333 pediatric LT performed, 51 children received an ABO-c graft. PLS was diagnosed in 7 (14%) subjects at a median of 10 days after LT. There were no significant differences in patient demographics, graft type, or immunosuppression between those who did and did not develop PLS. Recipient blood group A+ receiving a donor O+ graft was a risk factor for PLS (P = 0.015). All PLS subjects recovered with blood transfusions (median 2), and no additional interventions. Three subjects initially received recipient (instead of donor) blood group red cells. We report a 14% prevalence of PLS following pediatric ABO-c LT. Recipient blood group A+ receiving a donor O+ graft is a risk factor for PLS. Recognition of PLS as a cause of early acute anemia in pediatric ABO-c LT enables timely transfusion with donor (rather than recipient) blood group red cells.

Impact of the baseline anti-A/B IgG titer on the clinical outcome in ABO-incompatible liver transplantation

Introduction: The use of ABO incompatible (ABOi) living donors is an attractive solution for expanding the liver donor pool. We investigated the impact of the baseline anti-A/B IgG titer on the transplant outcomes in ABOi liver transplantation (LT). Method: We analyzed 394 adult patients who underwent living donor LT (303 ABO compatible LT and 91 ABOi LT) between 2012 and 2018. ABOi LT patients were categorized by baseline IgG titer: low IgG titer (≤ 1:64, n=51) versus high IgG titer (≥ 1:128, n=40). All ABOi LT patients received desensitization therapy including rituximab and plasmapheresis. Result: Patients with high IgG titer experienced antibody rebound (≥ 1:64) more frequently than those with low IgG titer during the first month after LT (35.0% vs. 15.7%, P=0.033). Patient survival rates for ABO compatible, low IgG titer, and high IgG titer were 85.0%, 91.5%, and 74.4%, respectively, at 3 years post-transplantation (P=0.006). High IgG titer (HR, 2.76; 95% CI, 1.39-5.48; P=0.004) and MELD score of >20 (HR, 2.32; 95% CI, 1.22-4.41; P=0.010) were independent risk factors for mortality. Infection was the leading causes of death in all groups, but the proportion was significantly higher in high IgG titer group than in other groups (81.8% vs. 30.8% vs. 33.3%). Conclusion: Patients with high IgG titer (≥ 1:128) are associated with a higher risk of death after ABOi LT than those with low IgG titer (≤ 1:64). Thus, ABOi LT patients with high IgG titer should be managed with great care.

Severe Passenger Lymphocyte Syndrome and Acute Rejection in ABO Compatible but non-Identical Liver Transplant Recipient from Hepatitis C Viremic Donor

We report a burdensome case of transplantation of a HCV-viremic liver graft into a HCV-viremic recipient with minor AB0 mismatch.

Intraoperative Management of a Patient With Impaired Cardiac Function Undergoing Simultaneous ABO-Compatible Liver and ABO-Incompatible Kidney Transplant From 2 Living Donors: A Case Report

BackgroundCombined liver and kidney transplant is a very complex surgery. To date, there has been no report on the intraoperative management of patients with impaired cardiac function undergoing simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors. Case ReportA 60-year-old man underwent simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors because of IgA nephropathy and alcoholic liver cirrhosis. The preoperative cardiac findings revealed continuous aggravation, shown by large left atrial enlargement, severe left ventricular hypertrophy, a very prolonged QT interval, and a calcified left anterior descending coronary artery. Severe hypotension with very weak pulsation and severe bradycardia developed, with an irregular junctional rhythm noted immediately after the liver graft was reperfused. Although epinephrine was administered as a rescue drug, hemodynamics did not improve, and central venous pressure and mean pulmonary arterial pressure increased to potentially fatal levels. Emergency phlebotomy via the central line was performed. Thereafter, hypotension and bradycardia recovered gradually as the central venous pressure and mean pulmonary arterial pressure decreased. The irregular junctional rhythm returned to a sinus rhythm, but the QTc interval was slightly more prolonged. Because of poor cardiac capacity, the volume and rate of fluid infusion were increased aggressively to maintain appropriate kidney graft perfusion after confirming vigorous urine production of the graft. ConclusionsA heart with impaired function due to both end-stage liver and kidney diseases may be less able to withstand surgical stress. Further study on cardiac dysfunction will be helpful for the management of patients undergoing complex transplant surgery.

Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection.

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation.

Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class II human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional anti-rejection therapy, can allow a rational approach to this threat.

Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis

Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long-term results, especially for hepatitis C virus (HCV)-positive recipients. This was a retrospective, single-center review of primary, ABO-compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60-69 years; 70-79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60-69 years; 233 (27.7%) with donors 70-79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60-69 years; 87.6% and 75.1% for grafts 70-79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5-year graft survival was lower for HCV-positive versus HCV-negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

The established procedure for ABO-incompatible liver transplantation (ABO-I LT) was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin (IVIG) for ABO-I LT in patients with acute liver failure (ALF). The data from 101 patients who had undergone liver transplantation (LT) for ALF were retrospectively analyzed. The patients were divided into two groups: ABO-compatible liver transplantation group (ABO-C LT, n=66) and ABO-I LT group (n=35). All the patients in the ABO-I LT group received a single dose of rituximab (375 mg/m2) and IVIG (0.4 g/kg per day) at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol. Quadruple immunosuppressive therapy including basiliximab, corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression. The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%, respectively (P>0.05), and the graft survival rates were 80.0% and 86.3%, respectively (P>0.05). Two patients (5.7%) suffered from antibody-mediated rejection in the ABO-I LT group. Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups. The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Antibody-mediated rejection in ABO compatible husband to wife living donor liver transplant and review of the literature

Role of donor specific antibodies (DSAs) in liver allograft function has not been fully defined. We report an ABO compatible orthotopic liver transplant case with DSAs to donor HLA, where the patient developed immediate antibody-mediated rejection (AMR).The patient, a 43-year-old female with cirrhosis, underwent ABO-compatible living-donor liver transplant from her husband. On post-operative day (POD)1, serum transaminases were sharply elevated. Retrospective testing of pre-transplant serum demonstrated presence of strong class I and class II anti-HLA antibodies and positive T- and B-cell flow-cytometric crossmatches (FCXM). Transaminase levels improved with plasmapheresis and thymoglobulin. On POD7, her liver enzymes became elevated again and allograft biopsy stained positive for C4d. Patient was treated with intravenous immunoglobulin and rituximab and recovered over time. Pre-transplant sera of patient were retrospectively tested by C1q assay to determine the cytotoxic function of DSAs; DSAs were positive for C1q binding. Our results suggest that pre-liver transplant antibody testing may be helpful in identifying patients at risk for development of AMR.

Pretransplant donor-specific anti-HLA antibodies as predictors of early allograft rejection in ABO-compatible liver transplantation

The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR). In the present study, we set out to determine whether pretransplant HLA-DSAs correlate with clinically significant ACR in the first 90 days after transplantation and, if so, to determine their predictive values. Class I HLA-DSAs and class II HLA-DSAs were determined by single-antigen bead flow cytometry for 113 consecutive adult transplants. A statistical analysis was performed for data from 109 consecutive patients with graft survival greater than or equal to 90 days. All patients who developed biochemical graft dysfunction underwent liver biopsy for hematoxylin-eosin and complement component 4d staining. Cox proportional hazards models and associated hazard ratios revealed a significant association of pretransplant HLA-DSAs with clinically significant ACR: this association started with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard ratio = 2.7, P < 0.01) and class II (hazard ratio = 6.0, P < 0.01). Pretransplant HLA-DSAs were associated with an increased risk of ACR: P < 0.01 for class I (42% versus 18%), P < 0.001 for class II (37% versus 7%), and P < 0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an MFI ≥ 1000 had the best positive predictive value for clinically significant ACR at 46%, whereas class I or II HLA-DSAs with an MFI ≥ 300 had the best negative predictive value at 97.1%. Although our study was based on consecutive patients, it was limited by the relatively low number of single-center subjects. In conclusion, the present study indicates that pretransplant HLA-DSAs, even at low levels of allosensitization, correlate with the risk of clinically significant ACR. Our findings suggest that anti-human leukocyte antigen antibodies could serve as donor-specific markers of immunoreactivity to the liver graft.

Bortezomib for Acute Antibody-Mediated Rejection in Liver Transplantation

Antibody-mediated rejection (AMR) is an uncommon, but challenging type of rejection after solid organ transplantation. We review three cases of AMR in ABO-compatible liver transplant recipients. These cases were characterized by severe acute rejection resistant to steroids and antithymocyte globulin, histologic evidence of plasma cell infiltrates, C4d positivity and high serum anti-HLA donor-specific antibodies. All three patients were treated with bortezomib, a proteasome inhibitor effective in depleting plasma cells. After treatment, all patients had improved or normal liver function tests, resolution of C4d deposition and significant decline in their HLA donor-specific antibodies.

Significance of complement split product C4d in ABO-compatible liver allograft: Diagnosing utility in acute antibody mediated rejection

Diagnosis of liver allograft antibody-mediated rejection (AMR) is difficult and requires a constellation of clinical, laboratory and histologic features that support the disease and exclude other causes. Histologic features of AMR may intermix with those of biliary obstruction, preservation/reperfusion injury, and graft ischemia. Tissue examination for complement degradation product 4d (C4d) has been proved to support this diagnosis in other allografts. For this reason, we conducted a retrospective review of all ABO compatible/identical re-transplanted liver patients with primary focus on identifying AMR as a possible cause of graft failure and to investigate the utility of C4d in liver allograft specimens. We reviewed 193 liver samples obtained from 53 consecutive ABO-compatible re-transplant patients. 142 specimens were stained with C4d. Anti-donor antibody screening and identification was determined by Luminex100 flow cytometry. For the study analysis, patients were stratified into 3 groups according to time to graft failure: group A, patients with graft failure within 0–7 days ( n = 7), group B within 8–90 days ( n = 13) and C > 90 days ( n = 33). Two patients (3.7%) met the diagnostic criteria of acute AMR. Both patients experienced rapid decline of graft function with presence of donor specific antibodies (DSA), morphologic evidence of humoral rejection and C4d deposition in liver specimens. C4d-positive staining was identified in different medical liver conditions i.e., acute cellular rejection (52%), chronic ductopenic rejection (50%), recurrent liver disease (48%), preservation injury (18%), and hepatic necrosis (54%). Univariate analysis showed no significant difference of C4d-positive staining among the 3 patients groups, or patients with DSA ( P > .05). In conclusion, AMR after ABO-compatible liver transplantation is an uncommon cause of graft failure. Unlike other solid organ allografts, C4d-positive staining is not a rugged indicator of humoral rejection, thus, interpretation should be done with caution to avoid diagnostic dilemmas.

Late‐onset graft‐versus‐host disease after pediatric living‐related liver transplantation for Langerhans cell histiocytosis

GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.

ABO‐incompatible pediatric liver transplantation in very small recipients: Birmingham’s experience

Liver transplantation (LT) for very small recipients is challenging but in experienced centres, good results can be achieved. Despite the risk of antibody-mediated acute rejection, some studies have demonstrated the safety of ABO incompatible liver transplantation (ILT) in children and particularly in infants. The aim of our study was to describe the outcome of liver transplantation in infants <5 kg and the safety of using ILT in this group. All LT performed between 1991 and 2010 in children <5 kg were reviewed. Twenty-nine patients were included, five of whom had an ILT. Acute liver failure was encountered in 20 cases. The recipient age and weight at transplantation were respectively 63 days (range: 14-268 days) and 4 kg (range: 2.4-5 kg). The graft-to-recipient ratio was 6.1% (range 2.3-9%). An aortic conduit and delayed abdominal closure were used respectively in 76% and 81% of the procedures. The ABO compatible liver transplantation (CLT) and ILT groups were similar regarding recipient's demographics, graft types or technical transplantation data. The one- and five-yr patient and graft survival were respectively 62%, 62% and 62%, 57.9% with a median follow-up of 95 months. Vascular complications occurred in six cases (21.4%) and biliary complications were encountered in five patients (17%). Acute and chronic rejection developed respectively in 37% and 26% of the recipients. The five patients undergoing ILT are all alive without graft lost after a median follow-up of 34 months (range 7-55 months). When compared with the CLT group, no significant differences were found regarding patient or graft survival, vascular or biliary complications and rejection rates. In our experience, ILT in small infants has short and long term outcomes comparable to ABO-compatible grafts and excellent results can be achieved with a standard immunosuppressive protocol. To avoid mortality on the waiting list for neonatal recipients, ABO-incompatible liver grafts can be used safely.