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Abstract
By 2014, strategies to prevent antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) were established in Japan and expanded primarily to Asia, where LDLT is now the predominant form of LT owing to the scarcity of brain-dead donors. A desensitization protocol consisting of rituximab (375 mg/m 2 ), plasma pheresis, tacrolimus, and mycophenolate mofetil before LDLT, followed by standard immunosuppression, is currently the best option in terms of safety and efficacy. Rituximab administration is now known not to increase the risk of hepatocellular carcinoma recurrence, and the feasibility of rituximab for LDLT for acute liver failure and the need for desensitization before LDLT in children older than 1 y have been documented. Strategies are needed to distinguish patients at high risk of AMR from those at low risk and to adjust immunosuppression to prevent both AMR and infection. Specific single-nucleotide polymorphisms in genes encoding Fcγ receptors affecting the cytotoxicity of rituximab on B cells could be useful for adjusting immunosuppression levels to decrease infectious complications. Immunological accommodation after ABO-I transplantation could be provided by immune factors in both the grafts and recipients.
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Lin YC, Lin TS, Lin CC, Liu YW, Wang SH, Wu YJ, Li WF, Lin YH, Lin TL, Chan YC, Yeh CH, Wang CC, Chen CL, Yong CC. Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation? Ann Transplant 2021; 26:e931963. [PMID: 34446690 PMCID: PMC8406902 DOI: 10.12659/aot.931963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. Material/Methods From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. Results Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). Conclusions Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.
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Affiliation(s)
- Yu-Cheng Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsan-Shiun Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Ho Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Ju Wu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Hung Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ting-Lung Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Chia Chan
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Hsi Yeh
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Feasibility of Monotherapy by Rituximab Without Additional Desensitization in ABO-incompatible Living-Donor Liver Transplantation. Transplantation 2018; 102:97-104. [PMID: 28938311 DOI: 10.1097/tp.0000000000001956] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living-donor liver transplantation (ABO-i LDLT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion (LI) therapy were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT. METHODS Forty patients receiving ABO-i LDLT with rituximab were enrolled in this retrospective study. The patients were divided into 2 groups: the rituximab with pretransplant PP and posttransplant LI (RPL) group (n = 20) and the rituximab monotherapy (RM) without any additional treatment group (n = 20). The groups were then compared in terms of the rates of patient survival, antibody-mediated rejection (AMR), and infection. RESULTS The 1-, 3-, and 5-year patient survival rates were 85%, 85%, and 85% in the RPL group and 89%, 80%, and 80% in the RM group, respectively. There was no significant difference in patient survival between the 2 groups. There were no episodes of AMR in either group. The RM group had a lower rate of fungal and viral infections than the RPL group. CONCLUSIONS Pretransplant rituximab without additional treatments yielded satisfactory outcomes comparable to that with additional treatments, such as PP and LI.
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Rana A, Kueht ML, Nicholas SK, Jindra PT, Himes RW, Desai MS, Cotton RT, Galvan NTN, O'Mahony CA, Goss JA. Pediatric Liver Transplantation Across the ABO Blood Group Barrier: Is It an Obstacle in the Modern Era? J Am Coll Surg 2016; 222:681-9. [PMID: 27016995 DOI: 10.1016/j.jamcollsurg.2015.12.041] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2015] [Accepted: 12/21/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND The initial experience with ABO incompatible (ABOi) orthotopic liver transplantations (OLTs) was dismal. In the current study, we investigated whether ABOi pediatric OLTs could achieve acceptable patient outcomes. The option for ABOi transplantation is vital because critically ill children have limited access to donor liver allografts. STUDY DESIGN Kaplan-Meier and multivariate Cox analysis was performed on data collected from 13,179 pediatric OLT recipients in the United Network for Organ Sharing database, including 540 ABOi recipients. We also analyzed 18 pediatric recipients of ABOi OLTs at Texas Children's Hospital. Recipients were divided into 2 groups: transplanted between 1987 to 2002 (remote era) and 2002 to 2013 (modern era). RESULTS Analysis revealed 4 main points. First, there was a significant (p < 0.01) improvement in ABOi OLT survival in the modern era. Second, threshold analysis revealed superior outcomes (p < 0.01) for OLT recipients younger than 2 years of age. Third, survival outcomes for ABOi and ABO-identical OLTs were the same for recipients younger than 2 years: ABOi was 91.8% (1 year) and 88.4% (5 year), and ABO identical was 91.5% (1 year) and 86.7% (5 year) (p = 0.94). Lastly, we found identical OLT results when analyzing our own institutional experience. To date, there has been a 92.9% survival rate in the modern era compared with 75% in the remote era. All recipients younger than 2 years (n = 9) are still alive, compared with 78% of those older than 2 years. CONCLUSIONS This analysis revealed a significant improvement in the survival of ABOi liver transplant recipients in the modern era. Importantly, ABOi liver transplantation can be performed in recipients younger than 2 years of age with equivalent outcomes compared with ABO-identical recipients.
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Affiliation(s)
- Abbas Rana
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX.
| | - Michael L Kueht
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
| | - Sarah K Nicholas
- Division of Immunology, Allergy and Rheumatology, Department of Pediatric Medicine, Texas Children's Hospital, Houston, TX
| | - Peter T Jindra
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
| | - Ryan W Himes
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatric Medicine, Texas Children's Hospital, Houston, TX
| | - Moreshwar S Desai
- Division of Intensive Care, Department of Pediatric Medicine, Texas Children's Hospital, Houston, TX
| | - Ronald T Cotton
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
| | - N Thao N Galvan
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
| | - Christine A O'Mahony
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
| | - John A Goss
- Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, Houston, TX; Department of Surgery, Texas Children's Hospital, Houston, TX
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Diwan TS, Paterno F, Shah SA. Use of Extended Criteria Deceased Donors in Adult Liver Transplantation. CURRENT SURGERY REPORTS 2015. [DOI: 10.1007/s40137-015-0103-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Kornberg A. Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation. World J Hepatol 2015; 7:1494-1508. [PMID: 26085909 PMCID: PMC4462688 DOI: 10.4254/wjh.v7.i11.1494] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 04/19/2015] [Accepted: 05/08/2015] [Indexed: 02/06/2023] Open
Abstract
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients’ infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
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Lee SD, Kim SH, Kong SY, Kim YK, Lee SA, Park SJ. ABO-incompatible living donor liver transplantation without graft local infusion and splenectomy. HPB (Oxford) 2014; 16:807-13. [PMID: 24467804 PMCID: PMC4159453 DOI: 10.1111/hpb.12215] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 11/27/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Graft local infusion and splenectomy in ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) are associated with high rates of operative complications. METHODS Consecutive ABO-I LDLT patients treated at the National Cancer Centre between January 2012 and February 2013 were identified. The protocol for ABO-I LDLT at the study centre included the administration of rituximab (300 mg/m(2)) at 2 weeks preoperatively, followed by plasma exchanges (target isoagglutinin titre: ≤ 1:8), basiliximab (20 mg on the day of surgery and on postoperative day 4), and i.v. immunoglobulin (0.8 g/kg on postoperative days 1 and 4) without graft local infusion or splenectomy. RESULTS Fifteen patients (11 men and four women) who underwent transplantation for liver cirrhosis (n = 3) or hepatocellular carcinoma (n = 12) were identified. These included 13 patients with hepatitis B virus infection, one with hepatitis C virus infection and one with alcoholic cirrhosis. The mean age, mean Model for End-stage Liver Disease (MELD) score and mean graft-to-recipient weight ratio (GRWR) of these patients was 51.8 years, 11.5 and 0.84, respectively. The median isoagglutinin titre before plasma exchange was 1:32 (range: 1:4 to 1:256). There were no hyperacute or antibody-mediated rejections. No bacterial or fungal infections were observed. Complications included herpes zoster viral infection in one patient, postoperative bleeding in one patient and extrahepatic biliary stricture in three patients. CONCLUSIONS This simplified ABO-I LDLT protocol showed good graft outcomes without immunologic failure or serious infections.
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Affiliation(s)
- Seung Duk Lee
- Centre for Liver Cancer, National Cancer CentreGoyang-si, South Korea
| | - Seong Hoon Kim
- Centre for Liver Cancer, National Cancer CentreGoyang-si, South Korea,Correspondence, Seong Hoon Kim, Centre for Liver Cancer, Research Institute and Hospital, National Cancer Centre, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea. Tel: + 82 31 920 1647. Fax: + 82 31 920 1379. E-mail:
| | - Sun-Young Kong
- Department of Laboratory Medicine, National Cancer CentreGoyang-si, South Korea
| | - Young-Kyu Kim
- Centre for Liver Cancer, National Cancer CentreGoyang-si, South Korea
| | - Soon-Ae Lee
- Centre for Liver Cancer, National Cancer CentreGoyang-si, South Korea
| | - Sang-Jae Park
- Centre for Liver Cancer, National Cancer CentreGoyang-si, South Korea
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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ABO-incompatible living donor liver transplantation is suitable in patients without ABO-matched donor. J Hepatol 2013; 59:1215-22. [PMID: 23928408 DOI: 10.1016/j.jhep.2013.07.035] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2013] [Revised: 07/19/2013] [Accepted: 07/21/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS ABO-incompatible liver transplantation is usually contraindicated because of the risk of antibody-mediated humoral rejection of the graft. We describe 22 successful cases of patients who had living donor liver transplantation (LDLT) from ABO-incompatible donors. METHODS The immunosuppressive protocol consisted of rituximab and plasmapheresis prior to LDLT. Plasmapheresis was planned for up to 2 weeks after LDLT aiming at maintaining levels of anti-ABO titers below 1:32. RESULTS The median age of recipients was 54 years and the median MELD score was 13. The initial range of isoagglutinin IgM and IgG titers were 1:8-1:1024 and 1:2-1:1024, respectively. Preoperative isoagglutinin IgM and IgG titers were achieved less than or equal to 1:8 by performing therapeutic plasma exchange (TPE). While the median number of TPE was 4 (range, 2-18) in all patients, it was 4 (range, 2-8) in the initial low titer group (<1:256) and 8 (range, 6-18) in the high titer group (≥ 1:256). There were no statistically significant differences for liver function tests in the first 2 weeks after transplantation between the groups having high MELD score (≥ 20) vs. low MELD score (<20), local graft infusion vs. systemic infusion, or high initial isoagglutinin titer (≥ 1:256) vs. low initial isoagglutinin titer (<1:256). Patient and graft survival was 100% and there was no acute humoral rejection in recipients at a mean follow-up of 10months (range, 3-21). CONCLUSIONS ABO-incompatible LDLT can be safely performed when rituximab and TPE are used, and may be proposed when ABO-compatible donors are not available.
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ABO-incompatible liver transplantation in acute liver failure: a single Portuguese center study. Transplant Proc 2013; 45:1110-5. [PMID: 23622639 DOI: 10.1016/j.transproceed.2013.02.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION ABO-incompatible liver transplantation (ABOi LT) is considered to be a rescue option in emergency transplantation. Herein, we have reported our experience with ABOi LT including long-term survival and major complications in these situations. PATIENT AND METHODS ABOi LT was performed in cases of severe hepatic failure with imminent death. The standard immunosuppression consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Pretransplantation patients with anti-ABO titers above 16 underwent plasmapheresis. If the titer was above 128, intravenous immunoglobulin (IVIG) was added at the end of plasmapheresis. The therapeutic approach was based on the clinical situation, hepatic function, and titer evolution. A rapid increase in titer required five consecutive plasmapheresis sessions followed by administration of IVIG, and at the end of the fifth session, rituximab. RESULTS From January 2009 to July 2012, 10 patients, including 4 men and 6 women of mean age 47.8 years (range, 29 to 64 years), underwent ABOi LT. At a mean follow-up of 19.6 months (range, 2 days to 39 months), 5 patients are alive including 4 with their original grafts. One patient was retransplanted at 9 months. Major complications were infections, which were responsible for 3 deaths due to multiorgan septic failure (2 during the first month); rejection episodes (4 biopsy-proven of humoral rejections in 3 patients and 1 cellular rejection) and biliary. CONCLUSION The use of ABOi LT as a life-saving procedure is justifiable in emergencies when no other donor is available. With careful recipient selection close monitoring of hemagglutinins and specific immunosuppression we have obtained acceptable outcomes.
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Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab. Transplantation 2012; 93:99-105. [PMID: 22094955 DOI: 10.1097/tp.0b013e318239e8e4] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Preformed anti-ABO antibodies are primarily responsible for antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. METHODS Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6 ± 35.8 mg rituximab 17.7 ± 11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0 ± 10.3 mg rituximab 26.6 ± 21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. RESULTS Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the "splenectomy" and "nonsplenectomy" groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. CONCLUSIONS Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab.
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Survival after liver transplantation using hepatitis C virus-positive donor allografts: case-controlled analysis of the UNOS database. World J Surg 2011; 35:1590-5. [PMID: 21384242 DOI: 10.1007/s00268-011-1019-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Numerous reports have documented reduced graft and patient survival after use of hepatitis C (HCV) seropositive allografts in liver transplantation (OLT). We aimed to examine if the use of a HCV+ liver allograft affects patient and graft survivals compared to HCV- donor allografts in a case-controlled analysis of the united network for organ sharing (UNOS) database. METHODS We examined 63,149 liver transplants (61,905 donors HCV-; 1,244 donors HCV+) from the UNOS standard transplant analysis and research (STAR) file from 1987 to 2007. Donor and recipient demographics and outcomes were collected in which donor HCV serology was complete. A case-controlled cohort from 11 donor and recipient variables comparing donor HCV- and HCV+ allografts (n=540 in each group) was created using propensity scores with a matching algorithm. Graft and patient survival was estimated using Kaplan-Meier survival curves. RESULTS Significant differences were evident in the unadjusted cohort between recipients who received HCV+ and HCV- allografts, including HCV+ recipients, donor and recipient age, and model for end-stage liver disease (MELD) exception cases. Use of HCV+ allograft resulted in significantly lower graft survival (8.1 vs. 10.6 years; P=0.001) and patient survival (10.2 vs. 12.3 years; P=0.01) after OLT. In the matched cohort, HCV seropositivity had no detrimental effect on the graft (P=0.57) or patient (P=0.78) survival after OLT. CONCLUSIONS This is the first population-based analysis to show that after adjusting for donor and recipient characteristics there was no difference in graft or patient survival with the use of HCV+ donor liver allografts compared to HCV- donor liver allografts.
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Raut V, Uemoto S. Management of ABO-incompatible living-donor liver transplantation: past and present trends. Surg Today 2011; 41:317-22. [PMID: 21365409 DOI: 10.1007/s00595-010-4437-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2010] [Accepted: 08/12/2010] [Indexed: 12/30/2022]
Abstract
Based on the concept that the liver is a "privileged organ," which resists acute rejection, Thomas Starzl introduced liver transplantation across the ABO blood group. However, with improved survival after liver transplantation came reports of an increased incidence of acute rejection, biliary and vascular complications, and decreased survival after ABO-incompatible liver transplantation. As a result, ABO-incompatible liver transplantations are performed only in emergencies when ABO-compatible grafts are unavailable. In living-donor liver transplantation (LDLT), donors are restricted to family members; therefore, breaking ABO blood group barriers becomes inevitable. This inevitable situation has forced liver transplant surgeons to exploit many innovative techniques to overcome the challenges of ABO-incompatible liver transplantation. This review looks at the history and current practices of ABO-incompatible LDLT to provide insight so that the protocol can be improved further.
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Affiliation(s)
- Vikram Raut
- Department of Hepatobiliary-Pancreatic Surgery and Transplantation, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Abstract
Histological assessments continue to play an important role in the diagnosis and management of liver allograft rejection. The changes occurring in acute and chronic rejection are well recognized and liver biopsy remains the 'gold standard' for diagnosing these two conditions. Recent interest has focused on the diagnosis of late cellular rejection, which may have different histological appearances to early acute rejection and instead has features that overlap with so-called 'de novo autoimmune hepatitis' and 'idiopathic post-transplant chronic hepatitis'. There is increasing evidence to suggest that 'central perivenulitis' may be an important manifestation of late rejection, although other causes of centrilobular necro-inflammation need to be considered in the differential diagnosis. There are also important areas of overlap between rejection and recurrent hepatitis C infection and the distinction between these two conditions continues to be a problem in the assessment of liver allograft biopsies. Studies using immunohistochemical staining for C4d as a marker for antibody-mediated damage have found evidence of C4d deposition in liver allograft rejection, but the functional significance of these observations is currently uncertain. This review will focus on these difficult and controversial areas in the pathology of rejection, documenting what is currently known and identifying areas where further clarification is required.
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Affiliation(s)
- Desley A H Neil
- Department of Pathology, University of Birmingham, Birmingham, UK
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Goralczyk AD, Obed A, Schnitzbauer A, Doenecke A, Tsui TY, Scherer MN, Ramadori G, Lorf T. Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German Single Center Experience. J Transplant 2010; 2009:759581. [PMID: 20148072 PMCID: PMC2817542 DOI: 10.1155/2009/759581] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2009] [Accepted: 10/18/2009] [Indexed: 01/11/2023] Open
Abstract
Adult living donor liver transplantations (ALDLTs) across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins) were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR). Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety.
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Affiliation(s)
- Armin D. Goralczyk
- Department of General and Visceral Surgery, University Medical Center Göttingen, 37099 Göttingen, Germany
| | - Aiman Obed
- Department of General and Visceral Surgery, University Medical Center Göttingen, 37099 Göttingen, Germany
| | - Andreas Schnitzbauer
- Department of Surgery, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Axel Doenecke
- Department of Surgery, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Tung Yu Tsui
- Department of Surgery, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
- Department of Hepatobiliary and Transplant Surgery, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
| | - Marcus N. Scherer
- Department of Surgery, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Giuliano Ramadori
- Department of Gastroenterology, University Medical Center Göttingen, 37099 Göttingen, Germany
| | - Thomas Lorf
- Department of General and Visceral Surgery, University Medical Center Göttingen, 37099 Göttingen, Germany
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Chaib E, Fridman C, Massad E. Potential effect of using ABO-compatible living-donor liver transplantation. Transplant Proc 2009; 41:3775-8. [PMID: 19917386 DOI: 10.1016/j.transproceed.2009.05.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2009] [Accepted: 05/20/2009] [Indexed: 10/20/2022]
Abstract
Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.
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Affiliation(s)
- E Chaib
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
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Abstract
Liver transplantation has become a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure. The satisfactory outcome of liver transplantation has led to insufficient supplies of deceased donor organs, particularly in East Asia. Hence, East Asian surgeons are concentrating on developing and performing living-donor liver transplantation (LDLT). This review article describes an update on the present status of liver transplantation, mainly in adults, and highlights some recent developments on indications for transplantation, patient selection, donor and recipient operation between LDLT and deceased-donor liver transplantation (DDLT), immunosuppression, and long-term management of liver transplant recipients. Currently, the same indication criteria that exist for DDLT are applied to LDLT, with technical refinements for LDLT. In highly experienced centers, LDLT for high-scoring (>30 points) Model of End-Stage Liver Disease (MELD) patients and acute-on-chronic liver-failure patients yields comparably good outcomes to DDLT, because timely liver transplantation with good-quality grafting is possible. With increasing numbers of liver transplantations and long-term survivors, specialized attention should be paid to complications that develop in the long term, such as chronic renal failure, hypertension, diabetes mellitus, dyslipidemia, obesity, bone or neurological complications, and development of de novo tumors, which are highly related to the immunosuppressive treatment.
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Affiliation(s)
- Deok-Bog Moon
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Paulo DNS, Paulo IC, Morais AAC, Kalil M, Guerra AJ, Colnago GL, Faintuch J. Is splenectomy a dyslipidemic intervention? Experimental response of serum lipids to different diets and operations. Microsurgery 2009; 29:154-60. [DOI: 10.1002/micr.20568] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-beta-galactosidase (ABase) for ABO-incompatible transplantation. Transpl Immunol 2008; 20:132-8. [PMID: 18838121 DOI: 10.1016/j.trim.2008.09.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2008] [Revised: 09/10/2008] [Accepted: 09/10/2008] [Indexed: 01/18/2023]
Abstract
BACKGROUND ABO incompatibility in organ transplantation is still a high risk factor for antibody-mediated rejection, despite the progress in effective treatments. We have explored the possibility of using the enzyme to remove the blood type A/B antigen in organs. METHODS Recombinant endo-beta-galactosidase (ABase), which releases A/B antigen, was produced in E. coli BL-21. Human A/B red blood cells (RBC) were digested with ABase, and subjected to flow cytometric analysis after incubation with human sera. Purified recombinant ABase was intravenously administered to a baboon. Biopsies were taken from kidney and liver before and 1, 4 and 24 h after in vivo administration. Excised baboon kidneys were perfused with cold UW solution+/-purified recombinant ABase and preserved at 4 degrees C. Biopsies were taken before and 1 and 4 h after ex vivo perfusion. The change in A/B antigen expression was analyzed by immunohistochemical study. RESULTS ABase removed 82% of A antigen and 95% of B antigen in human A/B red blood cells, and suppressed anti-A/B antibody binding and complement activation effectively. ABase was also found to remain active at 4 degrees C. In vivo infusion of ABase into a blood type A baboon demonstrated a marked reduction of A antigen expression in the glomeruli of kidney (85% at 1 h, 9% at 4 h and 13% at 24 h) and the sinusoids of liver (47% at 1 h, 1% at 4 h and 3% at 24 h) without serious adverse effects. After ex vivo perfusion and cold storage of excised baboon kidney (blood type B) with ABase, the expression levels of B antigen in glomeruli were reduced to 49% at 1 h and 6% at 4 h. CONCLUSIONS This alternative approach might be useful for minimizing antibody removal and anti-B cell immunosuppression as an adjuvant therapy in ABO-incompatible kidney, liver and possibly heart transplantation.
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