ABO-incompatible Liver Transplantation Research Articles

ABO-incompatible liver transplantation – exploring utilitarian solutions to restricted access and organ shortages: A single-centre experience from Johannesburg, South Africa

Background. Liver transplantation is the definitive management for severe acute liver failure refractory to supportive management, and end- stage chronic liver failure. Owing to a shortage of deceased liver donors, South Africa requires innovative techniques to broaden the donor pool. Objectives. This study evaluated the outcomes of the Wits Transplant Unit ABO-incompatible liver transplant (ABOi-LT) programme. Methods. This retrospective record review compared all adult and paediatric patients receiving ABO-compatible (ABOc) and ABO-incompatible (ABOi) liver transplants from January 2014 to December 2021 with a minimum one-year follow-up. Primary outcomes were recipient and graft survival and secondary outcomes included vascular, enteric and biliary complications, relook surgery, acute cellular rejection (ACR) and lenghth of hospital stay. Cox proportional hazards regression was performed to examine the effect of ABO-compatibility group on recipient and graft survival. The relationship between the ABO-compatibility group and categorical outcomes was assessed by binomial regression. Results. During the study period, 532 liver transplants were performed; 44/532 (8%) were ABOi of which 14/44 (32%) were paediatric and 30/44 (68%) adult recipients. Within the pediatric group, the proportion of transplants performed for acute liver failure was significantly higher in the ABOi group (7/14; 50%) compared with the ABOc group (33/207; 16%) (p=0.005). Comparable recipient and graft survival estimates were noted: one-, three- and five-year recipient survival in the ABOi group was 77% (95% confidence interval (CI) 44 - 92), 58% (95% CI 17 - 84) and 58% (95% CI 17 - 84) respectively. There were significantly increased relative risks of relook surgery for the ABOi group compared with the ABOc group, both overall (relative risk (RR) 1.74; 95% CI 1.10 - 2.75) and at 90 days (RR 2.28; 95% CI 1.27 - 4.11); and also, for pre-discharge bloodstream infection (BSI), (RR 1.84; 95% CI 1.11 - 3.06). In adults, there were significantly more acute indications for liver transplantation in the ABOi (10/30; 33%) compared with the ABOc group (26/281; 9%) (p=0.0007) with the most common cause being drug or toxin ingestion (16/36; 44%). For the ABOi group, recipient survival estimates (95% CI) at 1, 3 and 5 years were 71% (50 - 84), 63% (41 - 78) and 58% (37 - 75) which, as noted with complication rates, were similar between ABO groups. Conclusion. This study confirms ABOi-LT as a feasible option to increase the liver donor pool in this organ-depleted setting as recipient survival and complication rates were similar between ABO-compatibility groups.

The paediatric liver transplant experience in Johannesburg, South Africa: A broad overview and update

Background: The Wits Transplant Unit performed its first paediatric liver transplant in 2005. Initial experiences from the unit were published in 2012 and 2014. Since then, significant progress has been made in capacity-building the unit, improving outcomes and enhancing service delivery. This paper presents a broad overview and update of the unit’s 17-year experience. Methods: We conducted a retrospective review of all paediatric liver transplants performed in Johannesburg from 1 January 2005 to 31 December 2021 with a minimum one-year follow-up. Data were accessed from the Wits Donald Gordon Medical Centre Paediatric Liver Transplant Research Database (University of the Witwatersrand Human Research Ethics approval: M190749). The following data were collected: donor and recipient sociodemographic and clinical characteristics, details of transplant procedures, donor grafts and recipient outcomes (post-operative complications, graft and recipient survival). Results: A total of 270 transplants were performed during the review period. Two thirds of recipients (n=180, 67%) were younger than 5 years at time of transplant and half (n=135, 50%) received a living donor graft. The most common indication for liver transplant was biliary atresia, followed by acute liver failure. Unadjusted recipient survival was 80% (95% CI: 75-85%) at one year, and 68% (95% CI: 59-75%) at five years. Waiting list mortality decreased from 27.3% in 2017 to 5.9% in 2021. One hundred and fifty-four (57.0%) recipients experienced at least one type of intervention requiring surgical complication - the most common being biliary in nature (n = 91; 33.7%). Conclusion: Over last seventeen years, a sustainable paediatric liver transplantation service has been established in Johannesburg. Living donor, split and ABO incompatible liver transplants have been incorporated in response to the severe organ shortage in South Africa. However, our outcomes can be improved. Additionally, a national transplant initiative to coordinate timeous referrals and expand access to liver transplantation for children with severe acute and chronic liver failure is advised.

Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation.

Clinical factors predicting graft survival (GS) after ABO-incompatible (ABOi) liver transplantation (LT), and differences between recipients with and without hepatocellular carcinoma (HCC) are unclear. To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without HCC) in ABOi living-donor liver transplantation (LDLT). We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT, including 47 patients with HCC. The 1-, 3-, 5-, and 10-year GS rates were 85.9%, 73.3%, 71.4%, and 71.4%, respectively, and there were no significant differences between HCC and non-HCC recipients. In multivariate Cox-regression analyses, tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT, in addition to the antibody-mediated rejection (AMR) were associated with poor-graft outcomes. In HCC patients, AMR [hazard ratio (HR) = 63.20, P < 0.01] and HCC recurrence (HR = 20.72, P = 0.01) were significantly associated with poor graft outcomes. HCCs outside Milan criteria, and tacrolimus concentrations at 4 wk post-LT > 7.3 ng/mL were significant predictive factors for HCC recurrence. After propensity score matching, patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival. Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence. Therefore, careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

ABO Incompatible Living Donor Liver Transplantation in Children: A Single Centre Experience from India

BackgroundIn recent years, pediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report pediatric ABOi LT experience including short- and long-term outcomes. MethodsIt is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n=20) and non-ABOi (n=220) pediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. ResultsOut of 239 pediatric LDLT from 2017-2022, 19 children (11 females) underwent 20 ABOi LT (including one retransplant with ABOi domino allograft) at a median age of 12(12,51) months with majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day -14 to day -1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture proven sepsis, biliary and vascular complications were seen in 10%, 20%, 20%, and 15% respectively. None of the ABOi LT recipients developed antibody mediated rejection. ABOi LT recipients as compared to non ABOi LT had higher incidence of bile leak and prolonged hospital stay with rest of the complications including biliary strictures and long-term outcome being comparable. At a median follow up of 21(14,33) months, 4 children expired (21%). ConclusionABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when compatible liver is unavailable.

Liver Transplantation for Zellweger Syndrome.

Zellweger syndrome or cerebrohepatorenal syndrome is a rare, multisystem disorder occurring due to defect in metabolic pathway within the peroxisomes. Cirrhosis with portal hypertension is an important presentation of these patients. Given its progressive, multisystem nature, the role of liver transplantation (LT) in Zellweger syndrome remains undefined and controversial. An 11-y-old boy diagnosed with Zellweger syndrome presented to theauthors with decompensated cirrhosis along with bilateral proptosis. After a meticulous evaluation, he was offered an ABO incompatible liver transplantation with hismother being the donor. He had an uneventful post operative period. After a follow up of 24 mo, he has normal graft function,normal cognition along with resolution of proptosis. Therefore, in a group of carefully selected patients with Zellweger syndrome, a liver transplantation can be offered successfully with an excellent prognosis.

I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation

Background and objectivesABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. MethodsThe survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. ResultsResults were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. ConclusionWith increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

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).

The association of early postoperative complications after ABO-incompatible liver transplantation and intraoperative red blood cell transfusion

The association of early postoperative complications after ABO-incompatible liver transplantation and intraoperative red blood cell transfusion

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

BK viraemia as a cause of anaemia in after ABO-incompatible liver transplant: a case report

BackgroundWhile anaemia following liver transplant is common, anaemia in the context of BK viraemia is not a commonly recognised phenomenon.Case presentationWe present the case of 59-year old gentleman with severe anaemia in the context of BK viraemia and nephropathy following ABO incompatible liver transplant. Severity of anaemia appeared to correlate with high titres of BK virus in the serum. Bone marrow biopsy revealed hypocellular marrow with normal cytogenetics. Anaemia improved with treatment with cidofovir, intravenous immunoglobulin, reduction in immunosuppression and erythropoietin stimulating agent.ConclusionTo our knowledge, this is the first case of anaemia post liver transplant contributed to by BK viraemia.

Rituximab administration one week before ABO-incompatible liver transplantation due to drug-induced acute liver failure with hepatic coma: a case report.

In cases of acute liver failure (ALF) with hepatic coma, early liver transplantation, including ABO-incompatible (ABOi) living donor liver transplantation (LDLT), should be considered. The ABO antibody barrier can be reduced using plasma exchange (PE) and the anti-CD20 antibody rituximab. Plasma exchange is also performed for drug-induced ALF and is effective for desensitization. Rituximab treatment usually requires 14days. There is presently no established desensitization protocol for ABOi-LDLT for ALF. Here, we report a case of drug-induced ALF with hepatic coma, which was treated with ABOi-LDLT using PE and rituximab 8days prior to surgery. A 33-year-old female, with a history of headaches for which she was taking analgesics daily, developed drug-induced ALF with hepatic coma. Her ABOi sister desired to become a liver donor. We initiated desensitization using rituximab (500mg) and mycophenolate mofetil (MMF, 2000mg/day), followed by five sessions of PE. Eight days after rituximab administration, ABOi-LDLT with splenectomy was performed. Postoperatively, the patient received local infusion via portal vein for 14days and immunosuppression with tacrolimus, methylprednisolone, and MMF. No episode of cellular or antibody-mediated rejection (AMR) was observed. The patient was discharged uneventfully 56days after ABOi-LDLT with no problems up to 15months after the transplant.

THU-513 - Pre-transplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation

THU-513 - Pre-transplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation

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.

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

Large volume plasmapheresis using a single-use immunoadsorption column: A cost-effective approach for desensitization in ABO-incompatible liver transplant.

Liver transplant is a life-saving treatment, but due to the limited availability of suitable liver donors, ABO-incompatible liver transplants (ABOi-LT) are conducted to increase the availability of liver donors. Perioperative desensitization for ABOi-LT is an established strategy to circumvent the risk of graft rejection. A single prolonged session can be performed to achieve the desired titers to avoid using multiple immunoadsorption (IA) columns or off-label reuse of single-use columns. This study retrospectively assessed the effectiveness of a single prolonged plasmapheresis session using IA as a desensitization strategy in live donor liver transplant (LDLT). This retrospective observational study conducted at a center for liver diseases in North India on six ABOi-LDLT patients who underwent single prolonged IA sessions in the perioperative period from January 2018 to June 2021. Median baseline titer in patients was 320 (64, 1024). The median plasma volume adsorbed was 7.5 volumes (4, 8) per procedure, with a mean procedure time of 600 min (310-753). The reduction in titer ranged from 4 log to 7 log reduction per procedure. Two patients developed transient hypotension during the procedure, which was managed successfully. The median duration of pre-transplant hospital stay was 1.5 days (1, 3). Desensitization therapy helps overcome the ABO barrier and decreases the waiting period before a transplant when ABO identical donors are unavailable. A single prolonged IA session reduces the cost of additional IA columns and hospital stay, thus making it a cost-effective approach to desensitization.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

Human immunodeficiency virus (HIV)-positive patients coinfected with hepatitis B virus (HBV) are eligible for liver transplantation (LT) in Africa and Southeast Asia, particularly China. However, the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT (ABOi-LT) is unknown. To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with end-stage liver disease (ESLD). We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT. The pretransplantation HIV viral load was undetectable, with no active opportunistic infections. Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses, followed by an intraoperative regimen of intravenous immunoglobulin, methylprednisolone, and basiliximab. Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil, and prednisone. At the intermediate-term follow-up, patients showed undetectable HIV viral load, CD4(+) T cell counts greater than 150 cells/μL, no HBV recurrence, and stable liver function. A liver allograft biopsy showed no evidence of acute cellular rejection. Both patients survived at 36-42 mo of follow-up. This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes, suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

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.

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.

Pretransplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation.

Intrahepatic cholangiopathy is a life-threatening sequela of ABO-incompatible liver transplantation. We analyzed the clinical impact of pretransplant administration of mycophenolate mofetil in reducing intrahepatic cholangiopathy in ABO-incompatible liver transplantation. Patients who underwent living donor liver transplantation between 2010 and April 2022 were included. Pretransplant mycophenolate mofetil was started in November 2020. A comparison between patients who experienced intrahepatic cholangiopathy and who did not among ABO-incompatible transplantation was performed. Recipients of ABO-incompatible transplantations were categorized based on donor surgery into open, laparoscopy without pretransplant mycophenolate mofetil, and laparoscopy with pretransplant mycophenolate mofetil groups. Cox analysis of intrahepatic cholangiopathy was performed. A total of 234 ABO-incompatible transplantations were included. Intrahepatic cholangiopathy occurred in 1.1% (n=1/94), 13.3% (n=12/90), and 2.0% (n=1/50) of patients who received an ABO-incompatible liver with open surgery, laparoscopic donor surgery without pretransplant mycophenolate mofetil and laparoscopic donor surgery with pretransplant mycophenolate mofetil. ( p = 0.001) Multivariable analysis showed that transplantations involving a donor who underwent a laparoscopic hepatectomy and a recipient who did not receive pretransplant mycophenolate mofetil were associated with a higher risk of intrahepatic cholangiopathy (HR=13.449, CI=1.710-105.800, p = 0.02) compared with transplantations from donors who underwent open surgery. Transplantations involving a donor who underwent laparoscopic donor surgery and a recipient who received pretransplant mycophenolate mofetil resulted in no increased risk compared with transplantations from donors who underwent open surgery. (HR=5.307, CI=0.315-89.366, p = 0.25) Laparoscopic donor hepatectomy was a risk factor for intrahepatic cholangiopathy in ABO-incompatible liver transplantation, while pretransplant mycophenolate mofetil was related to risk reduction of intrahepatic cholangiopathy.

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.