ABO-incompatible Living Donor Liver Transplantation Research Articles

High Number of Plasma Exchanges Increases the Risk of Bacterial Infection in ABO-incompatible Living Donor Liver Transplantation.

Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs. A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group. The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection (P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001). A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.

An ABO-incompatible living donor liver transplant in an infant with acute liver failure in the Sri Lankan setting

Liver transplant (LT) is the standard therapy for medically refractory acute liver failure (ALF). Finding a deceaseddonor graft in an emergency is challenging and often overcome by living-donation. Blood group matching is practised for LT though ABO-incompatible liver transplant (ABOi-LT) is performed inselected circumstances. We report an infant who underwent successful ABOincompatible living donor LT for ALF of unknown aetiology. This being the country’s first ABOi-LT, the youngest LT recipient to date and the youngest receiving emergency LT for ALF; we describe the novel experience at a resource-limited setting in Sri Lanka (SL).

Intention-to-treat analysis for survival benefit of ABO-incompatible living-donor liver transplantation in patients with a high Model for End-stage Liver Disease score

Intention-to-treat analysis for survival benefit of ABO-incompatible living-donor liver transplantation in patients with a high Model for End-stage Liver Disease score

P5.1: Impact of the high baseline anti-A/B antibody titer on the clinical outcomes in ABO-incompatible living donor liver transplantation.

P5.1: Impact of the high baseline anti-A/B antibody titer on the clinical outcomes in ABO-incompatible living donor liver transplantation.

Factors associated with rituximab-mediated B cell depletion in ABO-incompatible adult living donor liver transplantation.

Pretransplant therapies such as rituximab and plasmapheresis have led to an increase in ABO-incompatible (ABOi) living donor liver transplantation (LDLT), thus helping to overcome organ shortages. This study evaluated the changes in anti-A/B titers and CD19 levels over time in patients undergoing ABOi LT and aimed to understand the effect of single-nucleotide polymorphisms (SNPs) in Fc gamma receptor (FcγR) on rituximab therapy. Two SNPs of FCGR2A (131H/R) and FCGR3A (158F/V) were identified. The clinical data on 44 patients who underwent ABOi LDLT between May 2019 and October 2021 at Seoul National University Hospital were reviewed retrospectively. Following desensitization with rituximab and subsequent LDLT, the anti-A/B titer recovered within 1 week, but decreased thereafter. The CD19 level increased at 3 months after LT. The genotyping data for FCGR3A (158F/V) indicated that two patients had the V/V genotype, and 42 had the F/V genotype. In the genotyping data for FCGR2A (131H/R), 21 patients had the H/H genotype, three had the R/R genotype, and 20 had the H/R genotype. However, there were no significant differences in anti-A/B and CD19 levels, bacteremia rates, T cell-mediated rejection, antibody-mediated rejection, or the survival rate among the FCGR2A types. There were significant changes in the anti-A/B titers and CD19 levels over time in each patient after ABOi LDLT. The difference in outcomes following LT according to the FcγR SNP type for rituximab was unclear. Further studies with larger sample sizes are needed to confirm the effect of FcγR SNPs on rituximab therapy.

Early Postoperative Varicella-Zoster Virus Encephalitis After Adult ABO-Incompatible Living Donor Liver Transplantation: A Case Report

There have never been any reports of adult varicella-zoster virus (VZV) encephalitis cases. Here, we report a case of VZV encephalitis after adult ABO-incompatible living donor liver transplantation (LDLT). A 38-year-old man with decompensated liver cirrhosis caused by the hepatitis C virus was referred to our hospital as an LDLT candidate. Rituximab was administered 3 weeks before the operation, and immunosuppression agents were administered 1 week before the LDLT. Plasma exchange was performed 3 times before the LDLT. The right lobe from his mother's liver was used for the ABO-incompatible LDLT. On postoperative day (POD) 9, vascular stenting for intraabdominal bleeding from the common hepatic artery was performed by interventional radiology and was followed by re-laparotomy for abdominal drainage of the hematoma. However, there were various degrees of continued bleeding thereafter. On POD 12, due to a convulsion seizure with loss of consciousness, the patient was started on anticonvulsant therapy. On POD 15, there was an increased frequency of convulsion attacks and a prolonged loss of consciousness. A lumbar puncture was performed on POD 20 due to the appearance of shingles. The positive polymerase chain reaction of the VZV-DNA from the cerebrospinal fluid was detected, and he was diagnosed with VZV encephalitis. He rapidly regained alertness, and there were no further observed convulsion attacks after administration of a steroid pulse and acyclovir. Brain magnetic resonance imaging performed on 2 subsequent postoperative months showed findings that matched with VZV encephalitis. He was discharged as he had recovered and was ambulatory 3 months after LDLT.

Initial high anti-ABO titer is a major red flag of bacterial infection in ABO-incompatible living donor liver transplantation

Initial high anti-ABO titer is a major red flag of bacterial infection in ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Long-term outcomes following ABO-incompatible living donor liver transplantation for acute liver failure: a single-center experience of over 20years.

Acute liver failure is a life-threatening condition for which ABO-incompatible living donor liver transplantation (ABOi-LDLT) is sometimes the only life-saving treatment option. We reviewed a single-center experience of adult ABOi-LDLT treatment for acute liver failure (ALF). Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups. There were 5 and 33 patients in the ALF and non-ALF groups, respectively. The ALF group received higher doses of steroids, underwent more rounds of plasma exchange (PE), and underwent transplantation for ALF with a shorter interval following preoperative rituximab (RTx) administration (median: 2 vs 13days; P < 0.05) than the non-ALF group. Preoperatively, CD19-positive lymphocytes in the peripheral blood were sufficiently depleted in all of the non-ALF group patients, whereas they were poorly depleted in the ALF group. Postoperatively, neither group suffered anti-donor blood-type antibody titer rebound or antibody-mediated rejection. The ALF group had a comparable 5-year survival rate to the non-ALF group (80.0% vs 77.9%). Despite the delayed preoperative administration of RTx, the ALF group showed an uneventful immunological response and acceptable long-term survival rate. Thus, ABOi-LDLT seems a viable treatment option for ALF.

Improved recurrence-free survival in patients with HCC with post-transplant plasma exchange.

Total plasma exchange (TPE) can play a role in cancer treatment by eliminating immune checkpoint inhibitors. This study investigated whether TPE improved oncological outcomes in patients with HCC who underwent ABO-incompatible living donor liver transplantation (LT). The study included 152 patients who underwent ABO-incompatible living donor LT for HCC between 2010 and 2021 at Samsung Medical Center. Overall survival was analyzed using the Kaplan-Meier curve, whereas HCC-specific recurrence-free survival (RFS) was analyzed using the cumulative incidence curve after propensity score matching. Cox regression and competing risks subdistribution hazard models were used to identify the risk factors associated with overall survival and HCC-specific RFS, respectively. The propensity score matching resulted in 54 matched pairs, grouped according to whether they underwent postoperative TPE [post-transplant TPE(+)] or not [post-transplant TPE(-)]. The 5-year HCC-specific RFS cumulative incidence was superior in the post-transplant TPE (+) group [12.5% (95% CI: 3.1%-21.9%)] compared with the post-transplant TPE(-) group [38.1% (95% CI: 24.4%-51.8%), p = 0.005]. In subgroup analysis for patients with microvascular invasion and those beyond the Milan criteria, the post-transplant TPE(+) group showed significantly superior HCC-specific survival. The multivariable analysis also showed that postoperative TPE had a protective effect on HCC-specific RFS (HR = 0.26, 95% CI: 0.10-0.64, p = 0.004) and that the more post-transplant TPE was performed, the better RFS was observed (HR = 0.71, 95% CI: 0.55-0.93, p = 0.012). Post-transplant TPE was found to improve RFS after ABO-incompatible living donor LT for HCC, particularly in advanced cases with microvascular invasion and beyond Milan criteria. These findings suggest that TPE may have a potential role in improving oncological outcomes in patients with HCC undergoing LT.

Single-dose eculizumab as part of a modified desensitization protocol for ABO-incompatible living donor liver transplantation.

Spaggiari, Mario1; Petrochenkov, Egor1; Bencini, Giulia1; Gaitonde, Sujata2; Benken, Jamie2; Guzman, Grace2; Berkes, Jamie2; Tzvetanov, Ivo1; Benedetti, Enrico1 Author Information

Initial high anti-ABO isoagglutinin titer is a major red flag of bacterial infection in ABO-incompatible living donor liver transplantation

Initial high anti-ABO isoagglutinin titer is a major red flag of bacterial infection in ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

A case of COVID-19 1 month after ABO-incompatible living donor liver transplantation

A case of COVID-19 1 month after ABO-incompatible living donor liver transplantation

Fatal disseminated mucormycosis due to Cunninghamella bertholletiae infection after ABO-incompatible living donor liver transplantation: a case report

BackgroundFungal infection may develop because of immunosuppression after organ transplantation, in which invasive types, such as Aspergillus and Mucorales, fungi cause morbidity. We present a case of disseminated mucormycosis due to Cunninghamella bertholletiae after ABO-incompatible living donor liver transplantation (LDLT).Case presentationA 47-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma underwent an ABO-incompatible LDLT using a graft procured from his son, who had a different blood type. Rituximab and mycophenolate mofetil were administered 3 weeks before LDLT as immunosuppressive therapy. Although liver graft function improved, mass-like infiltrates appeared in the lungs following intubation for > 1 week due to impaired consciousness. The brain magnetic resonance imaging findings were normal. Decreased ejection fraction and ST elevation were detected on echocardiography and electrocardiography, respectively. There was no dominant stenosis on coronary arteriography. The recipient underwent segmentectomy of the right lung 20 days after LDLT. C. bertholletiae was identified from a specimen using polymerase chain reaction, thus establishing a diagnosis of mucormycosis. Multiple infarctions in the brain, heart, and kidney developed within 2 weeks. Treatment with amphotericin B was ineffective. The patient developed circulatory collapse, and a temporary pacemaker and percutaneous coronary intervention were required for cardiac infarction. The recipient died of cardiac failure 27 days after the LDLT. Autopsy revealed disseminated mucormycosis involving the brain, thyroid, heart, lung, liver, gastrointestinal tract, and both kidneys. In addition, fungal endocarditis may have been responsible for septic emboli in multiple organs, resulting in multiple organ invasion. Hypothrombocytopenia was present since the pre-transplant period, and the recipient was diagnosed posthumously with myelodysplastic syndrome due to hereditary abnormalities. Multiple factors such as organ transplantation, bone marrow dysfunction, immunosuppression, and inadequate administration of antifungal reagents might have promoted mucormycosis development in our patient.ConclusionsMucormycosis by C. bertholletiae is a fatal complication; thus, early diagnosis and treatment are warranted before multiple organ invasion.

Clinical Analysis of ABO-Incompatible Living-Donor Liver Transplantation in Children

To evaluate the safety and clinical efficacy of ABO-incompatible living-donor liver transplantation (LDLT) in children. The clinical data of 62 children who underwent for the first time living donor liver transplantation in our hospital from April 2019 to July 2020 were retrospectively analyzed. According to the blood type matching of donor and recipient, the patients were divided into 3 groups, ABO-identical (ABO-Id, n=33), ABO-compatible (ABO-C, n=10) and ABO-incompatible (ABO-In, n=19), the median age of recipients in the three groups being 5 months. In the ABO-In group, 4 recipients whose condition was combined with liver failure and 2 recipients who had blood group antibody titers≥1∶32 received preoperative plasma exchange. All ABO-incompatible recipients had preoperative blood group antibody titers<1∶32. All recipients in the three groups underwent piggyback liver transplantation and received immunosuppressive and anticoagulation therapy. Postoperative follow-up was 5 to 20 months, the median being 12 months, measured until December 31, 2020 or until the date of death. Baseline clinical data, postoperative survival, and postoperative complications of recipients in the three groups were analyzed. There were no significant differences in age, gender, underlying disease, operation history, Child Pugh score, donor age, graft to recipient weight ratio (GR/WR), cold ischemia time, warm ischemia time, duration of surgery, intraoperative blood loss and the use of immunosuppressants among the recipients in the three groups (all P>0.05). There was one death in the perioperative period and two deaths in the postoperative period in the ABO-Id group. There was one death in the postoperative period in the ABO-C group. There was one death in the perioperative period and one death in the postoperative period in the ABO-In group. There was no significant difference in the overall cumulative survival rate among the three groups ( P>0.05). There were no significant differences in the incidence of postoperative infection, acute rejection, biliary anastomotic stenosis and vascular complications among the three groups ( P>0.05). ABO-In LDLT is an effective and safe treatment option that can effectively expand the pool of live donors for liver transplantation and save the life of children with end-stage liver disease.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

Acute coronary syndrome after liver transplantation in a young primary biliary cholangitis recipient with dyslipidemia: a case report

BackgroundPrimary biliary cholangitis (PBC) is a chronic, progressive liver disease associated with dyslipidemia. There is a consensus that PBC does not accelerate coronary artery disease despite high cholesterol levels, so the screening test for the coronary artery is not routinely performed before liver transplantation (LT). To date, no report has described the potential risk of PBC-related dyslipidemia for developing acute coronary syndrome (ACS) after LT.Case presentationA 40-year-old Asian female with a known history of PBC underwent ABO-incompatible living-donor LT, with her husband as the donor. Although she had high cholesterol and triglyceride levels that were refractory to medications, she passed all routine preoperative examinations, including cardiopulmonary function tests and infection screenings. One week after LT, she developed ACS with 90% stenosis of both the left anterior descending artery and left circumflex artery. Emergent stent implantation was successfully performed followed by dual antiplatelet therapy. The long history of PBC and associated severe dyslipidemia for 10 years would have accelerated the atherosclerosis, causing latent stenosis in the coronary artery. Inapparent stenosis might have become apparent due to unstable hemodynamics during the acute phase after LT.ConclusionsPBC-related dyslipidemia potentially brings a risk for developing ACS after LT. This experience suggests that the preoperative evaluation of the coronary artery should be considered for high-risk patients, especially those who have drug-resistant dyslipidemia.

Overcoming high pre-transplant isoagglutinin titers using high-dose intravenous immunoglobulin, salvage plasmapheresis, and booster rituximab without splenectomy in ABO-incompatible living donor liver transplantation: a case report

High pre-transplant isoagglutinin is a risk factor for antibody-mediated rejection in ABO-incompatible living donor liver transplantation. A 55-year-old man with alcoholic liver cirrhosis underwent ABO-incompatible living donor liver transplantation. The initial isoagglutinin immunoglobulin G titer was 1:1,024. Despite five sessions of plasmapheresis, the isoagglutinin titer was not significantly reduced (from 1:1,024 to 1:512). We decided to perform 11 plasmaphereses and proceed with liver transplantation regardless of the isoagglutinin titer (1:128 at transplantation day). Instead, we planned to administer 0.5 g/kg intravenous immunoglobulin and booster rituximab (200 mg) after transplant. On postoperative day 6, the isoagglutinin titer increased from 1:32 to 1:64, and the patient received plasmapheresis twice. The patient maintained stable liver function without evidence of further complications or rejection. The high-dose intravenous immunoglobulin, salvage plasmapheresis, and booster rituximab protocol might be able to overcome a pre-transplant high isoagglutinin titer in ABO-incompatible living donor liver transplantation without splenectomy.

Progress in living donor liver transplantation for biliary atresia and challenges faced: A thirty-year single institutional experience

BackgroundBiliary atresia (BA) is the most common indication for liver transplantation in the pediatric population, and living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) have been established as a radical treatment for BA .The aim of this study was to clarify the long term outcomes and risk factors affecting the LDLT outcomes, as well as the challenges faced. MethodsBetween 1990 and 2019, 666 BA patients underwent LDLT in our institution and were enrolled in this study. Data regarding the recipient's age, anatomic findings of the biliary tree at Kasai's portoenterostomy, basic characteristics at transplantation, transplant profiles, donor characteristics, and outcomes of LDLT were analyzed. ResultsThe 1-, 5-, 10-, 15-, 20-, and 25-year graft survival rates of BA patients who underwent LDLT were 88.1%, 85.4%, 81.5%, 78.9%, 76.6%, and 75.5%, respectively. The transplant era, age at transplantation, ABO incompatible transplant, and presence of pulmonary vascular complications were identified as significant risk factors for overall graft survival. When the study period was divided into the first (1990–1999) and second (2000–2019) phases and re analyzed, the outcomes of ABO-incompatible transplants and LDLT for adult BA patients remained inferior to others in the second phase. The 20-year graft survival rate in patients who underwent re transplantation in the second phase was 54.2%. ConclusionsThe outcomes of LDLT in children are generally good, but the immunosuppression procedures need to be further improved for ABO-incompatible cases in the future. Further improvements in LDLT results for adult patients and re transplantation remain challenges to be addressed in this field, and future attempts, including revision to the organ allocation system of deceased donors, are necessary. Level of evidenceLevel III (case control study).