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• W4313398545 abstract "Liver transplantation (LT) is a definitive treatment for the decompensated liver cirrhosis and fulminant liver failure. With limited availability of cadaveric liver allograft, ABO incompatible (ABOi) living donor liver transplantation (LDLT) plays an important part in further expansion of donor pool. Over the years, with the introduction of Rituximab and improving desensitisation protocol, outcomes of ABOi LDLT are on par with ABO compatible LT. However, ABOi LDLT protocol varies markedly from centre to centre. Intravenous Rituximab followed by plasmapheresis or immunoadsorption effectively reduce ABO isoagglutinins titre before transplant, thereby reducing the risk of antibody mediated rejection in the post-transplant period. Local infusion therapy and splenectomy are not used routinely at most of the centres in Rituximab era. Post-transplant immunosuppression usually consists of standard triple drug regime, and tacrolimus trough levels are targeted at higher level compared to ABO compatible LT. Introduction of newer therapies like Belatacept and Obinutuzumab hold promise to further improve outcomes and reduce the risk of antibody mediated rejection related complications. ABOi LT in emergency situations like acute liver failure and deceased donor LT is challenging due to limited time period for desensitisation protocol before transplant, and available evidence are still limited but encouraging. Liver transplantation (LT) is a definitive treatment for the decompensated liver cirrhosis and fulminant liver failure. With limited availability of cadaveric liver allograft, ABO incompatible (ABOi) living donor liver transplantation (LDLT) plays an important part in further expansion of donor pool. Over the years, with the introduction of Rituximab and improving desensitisation protocol, outcomes of ABOi LDLT are on par with ABO compatible LT. However, ABOi LDLT protocol varies markedly from centre to centre. Intravenous Rituximab followed by plasmapheresis or immunoadsorption effectively reduce ABO isoagglutinins titre before transplant, thereby reducing the risk of antibody mediated rejection in the post-transplant period. Local infusion therapy and splenectomy are not used routinely at most of the centres in Rituximab era. Post-transplant immunosuppression usually consists of standard triple drug regime, and tacrolimus trough levels are targeted at higher level compared to ABO compatible LT. Introduction of newer therapies like Belatacept and Obinutuzumab hold promise to further improve outcomes and reduce the risk of antibody mediated rejection related complications. ABOi LT in emergency situations like acute liver failure and deceased donor LT is challenging due to limited time period for desensitisation protocol before transplant, and available evidence are still limited but encouraging. Liver transplantation (LT) has become an established treatment for liver cirrhosis, acute liver failure and other end stage liver diseases. With growing cases of liver cirrhosis, gap between the demand and availability of liver allograft is continuing to rise. Because of limited availability of cadaveric graft, in many countries living donor liver transplantation (LDLT) has been the predominant form of liver transplant. The use of ABO incompatible (ABOi) grafts has led to further expansion of the donor pool. In geographical areas with scarcity of deceased donor organs, ABOi liver allograft may be the only potential option for sick patients who require urgent liver transplant. ABOi LDLT is now an important form of LT in East and Southeast Asia, contributing up to 10% or more in some of these countries.1Goss M.B. Rana A. ABO-incompatible liver transplantation: Is It a Viable Option With Modern Innovation?.Clinical Liver Disease. 2017; Crossref Scopus (12) Google Scholar, 2Ikegami T. Taketomi A. Soejima Y. et al.Rituximab, IVIG, and plasma exchange without graft local infusion treatment: a new protocol in ABO incompatible living donor liver transplantation.Transplantation. 2009; 88: 303-307Crossref PubMed Scopus (94) Google Scholar, 3Kawagishi N. Satoh K. Enomoto Y. et al.New strategy for ABO-incompatible living donor liver transplantation with anti-CD20 antibody (rituximab) and plasma exchange.Transplant Proc. 2005; 37: 1205-1206Crossref PubMed Scopus (31) Google Scholar Crossing of ABO barrier in human solid organ transplantation was first attempted by Dr. GP Alexandre in renal transplant in 1985.4Alexandre G.P.J. de Bruyere M. Squifflet J.P. Moriau M. Latinne D. Pirson Y. Human ABO-incompatible living donor renal homografts.Neth J Med. 1985; 28: 231-234PubMed Google Scholar Initial success rates of ABOi liver transplants in adults were low, and outcomes were disappointing. High mortality was mostly related with hyperacute rejection, antibody mediated rejection (AMR) related allograft loss and infections due to overimmunosuppression.5Song G.W. Lee S.G. Hwang S. et al.ABO-incompatible adult living donor liver transplantation under the desensitization protocol with rituximab.Am J Transplant. 2016; 16: 157-170Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar,6Oh J. Kim J.M. Immunologic strategies and outcomes in ABO-incompatible living donor liver transplantation.Clin Mol Hepatol. 2020; 26: 1-6Crossref PubMed Scopus (18) Google Scholar Initial successful results of ABOi LDLT involved the use of multiple plasmapheresis, splenectomy, local infusion therapy along with higher doses of multiple immunosuppressive drugs. Addition of Rituximab further improved the graft rejection rates.7Monteiro I. McLoughlin L.M. Fisher A. de La Torre A.N. Koneru B. Rituximab with plasmapheresis and splenectomy in abo-incompatible liver transplantation.Transplantation. 2003; 76: 1648-1649Crossref PubMed Scopus (43) Google Scholar, 8Nakamura Y. Matsuno N. Iwamoto H. et al.Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report.Transplant Proc. 2004; 36: 2269-2273Crossref PubMed Scopus (27) Google Scholar, 9Tanabe M. Shimazu M. Wakabayashi G. et al.Intraportal infusion therapy as a novel approach to adult ABO-incompatible liver transplantation.Transplantation. 2002; 73: 1959-1961Crossref PubMed Scopus (140) Google Scholar Over the years, with improving immunosuppression and introduction of various desensitisation protocols, outcomes of ABOi have improved markedly. Currently, graft survival and long-term outcomes of ABOi liver transplant are almost similar to the ABO compatible (ABOc) transplant.10Egawa H. Teramukai S. Haga H. et al.Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.Am J Transplant. 2014; 14: 102-114Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar,11Farges O. Kalil A.N. Samuel D. et al.The use of ABO-incompatible grafts in liver transplantation: a life-saving procedure in highly selected patients.Transplantation. 1995; 59: 1124-1133Crossref PubMed Google Scholar Desensitization protocols differ markedly from centre to centre. In this review, we will discuss pre- and peri transplant desensitisation protocols and strategies being used in ABOi liver transplant to minimise the risk of AMR. ABOi liver transplant has the risk of AMR that can manifest as graft dysfunction, rapid graft loss due to hepatic necrosis and non-anastomotic biliary strictures. ABO antigens are oligosaccharide structures, which are expressed on a wide variety of human tissues in addition to red blood cells, and are present on most epithelial and endothelial cells.12The ABO Blood Group - Blood Groups and Red Cell Antigens - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/sites/books/NBK2267/?msclkid=a5865a72cedb11eca29e053e58a41e84. Accessed 8 May 2022.Google Scholar,13Samuelsson B.E. Breimer M.E. ABH antigens: some basic aspects.Transplant Proc. 1987; 19: 4401-4407PubMed Google Scholar ABO blood antigens are primarily expressed over red blood cells, vascular endothelium and biliary epithelium.14Tanabe M. Kawachi S. Obara H. et al.Current progress in ABO-incompatible liver transplantation.Eur J Clin Invest. 2010; 40: 943-949Crossref PubMed Scopus (87) Google Scholar Preformed ABO antibodies present in recipient blood bind ABO antigens, expressing on donor tissue cells in allograft liver. Antigen antibody binding along with complement activation leads to inflammatory cascade with recruitment of platelets, neutrophils, macrophages and release of various cytokines and chemokines. This results in injury to vascular endothelium and vascular thrombi formation within the grafted liver. Impairment of blood circulation results in graft tissue and biliary ducts ischaemia, leading to liver necrosis, biliary strictures, cholestasis and ultimately graft loss.15Egawa H. Challenge to ABO blood type barrier in living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2020; 19: 342-348Crossref PubMed Scopus (10) Google Scholar AMR histopathology is characterised by endothelial cells injury within portal tract vasculature with periportal oedema, microvasculitis, endothelitis and microthrombi, with the development of parenchymal and biliary necrosis in more severe cases in later stage. After complement activation, C4d binds to endothelial tissues, and diffuse microvascular C4d deposition seen on immunohistochemical staining is one of the hall marks of AMR16Haga H. Egawa H. Shirase T. et al.Periportal edema and necrosis as diagnostic histological features of early humoral rejection in ABO-incompatible liver transplantation.Liver Transplant. 2004; 10: 16-27Crossref PubMed Scopus (85) Google Scholar, 17Haga H. Egawa H. Fujimoto Y. et al.Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation.Liver Transplant. 2006; 12: 457-464Crossref PubMed Scopus (111) Google Scholar, 18Lee M. Antibody-mediated rejection after liver transplant.Gastroenterol Clin N Am. 2017; 46: 297-309Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Post-transplant outcomes and graft survival primarily depend on the removal of preformed anti ABO antibodies in recipients before the liver transplant. Risk of post-transplant AMR, graft necrosis and biliary complications increased with high perioperative titre of anti A and anti B antibodies. Desensitization strategies aim to significantly reduce the titre of these anti ABO antibodies in recipients, leading to minimisation of graft rejection and related complications.19Kawagishi N. Satomi S. Current aspects of ABO-incompatible liver transplantation.Clin Case Rep Rev. 2016; https://doi.org/10.15761/ccrr.1000221Crossref Google Scholar,20Egawa H. Oike F. Buhler L. et al.Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation.Transplantation. 2004; 77: 403-411Crossref PubMed Scopus (162) Google Scholar Rituximab is an anti CD-20 chimeric murine monoclonal antibody, which is primarily being used in lymphomas, autoimmune and rheumatoid disorders. One of the first successful uses of Rituximab in ABOi solid organ transplant was reported by Tyden et al. in kidney transplantation.21Tydén G. Kumlien G. Fehrman I. Successful ABO-incompatible kidney transplantations without splenectomy using antigen-specific immunoadsorption and rituximab.Transplantation. 2003; 76: 730-731Crossref PubMed Scopus (250) Google Scholar After the success in kidney transplant, it was used in ABOi liver transplant. First reported use of Rituximab was by Monterio et al. in liver transplant.7Monteiro I. McLoughlin L.M. Fisher A. de La Torre A.N. Koneru B. Rituximab with plasmapheresis and splenectomy in abo-incompatible liver transplantation.Transplantation. 2003; 76: 1648-1649Crossref PubMed Scopus (43) Google Scholar Rituximab binds selectively to CD-20, which is expressed by most of the human B lymphocytes. CD 20 expression is not seen on stem cells, pro B cells and plasma cells, but stimulated plasma cells and plasma blast cells may express CD20. Binding of Rituximab on CD 20 positive cells results in cell injury and death via direct signalling, complement-dependent cellular toxicity and antibody-dependent cellular toxicity , leading to depletion of B cell population.22Weiner G.J. Rituximab: mechanism of action.Semin Hematol. 2010; 47: 115Crossref PubMed Scopus (565) Google Scholar,23Sood P. Hariharan S. Anti-CD20 blocker rituximab in kidney transplantation.Transplantation. 2018; 102: 44-58Crossref PubMed Scopus (21) Google Scholar B cells play multiple roles in the immune system like antibody production, cytokines productions as well as antigen producing cells. So, B cell depletions not only interrupt humoral but also T cells-mediated immune response.24Hoffman W. Lakkis F.G. Chalasani G. B cells, antibodies, and more.Clin J Am Soc Nephrol. 2016; 11: 137Crossref PubMed Scopus (252) Google Scholar,25von Bergwelt-Baildon M. Schultze J.L. Maecker B. et al.CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells. Cancer res 2003;63:2836-2843.Cancer Res. 2004; 64 (multiple letters) (4055–2843)Crossref PubMed Scopus (11) Google Scholar Rituximab is given as intravenous formulation in the standard dose of 375 mg/m2. Single dose is usually sufficient, and multiple administrations can increase the risk of infections.10Egawa H. Teramukai S. Haga H. et al.Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.Am J Transplant. 2014; 14: 102-114Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar Doses lower than 375 mg/m2 have also been used recently in some studies. In a small study by Egawa et al., Rituximab dose of 200 mg/m2 was not associated with the increased risk of AMR.26Egawa H. Umeshita K. Uemoto S. Optimal dosage regimen for rituximab in ABO-incompatible living donor liver transplantation.J Hepatobiliary Pancreat Sci. 2017; 24: 89-94Crossref PubMed Scopus (25) Google Scholar Lower dose can be considered in sick patients who have higher risk of infections. Rituximab has a long elimination half-life of about 3 weeks. Drug is usually given 2–3 weeks before the planned transplant surgery. Recent studies have shown that it can be given as early as 7 days before liver transplant with optimal outcomes. In emergency conditions, it has been given even within 72 h of surgery.10Egawa H. Teramukai S. Haga H. et al.Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.Am J Transplant. 2014; 14: 102-114Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar,27Egawa H. Ohmori K. Haga H. et al.B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation.Liver Transplant. 2007; 13: 579-588Crossref PubMed Scopus (90) Google Scholar,28Cheng C.-H. Lee C.-F. Wang Y.-C. et al.ABO-incompatible liver transplantation: state of art and future perspectives.Curr Pharmaceut Des. 2020; 26: 3406-3417Crossref PubMed Scopus (3) Google Scholar B cell depletion in peripheral blood starts within 48–72 h, however, complete depletion may take up to three weeks. The effect of Rituximab after single dose usually lasts for several months. Early administration has the advantage that dose can be repeated in case of inadequate response. Also, Rituximab can be eliminated by plasmapheresis when performed within 3 days of Rituximab administration.15Egawa H. Challenge to ABO blood type barrier in living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2020; 19: 342-348Crossref PubMed Scopus (10) Google Scholar,29Puisset F. White-Koning M. Kamar N. et al.Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody-mediated disease.Br J Clin Pharmacol. 2013; 76: 734-740Crossref PubMed Scopus (59) Google Scholar Administration of a single dose of Rituximab usually results in complete long-term elimination of B cells and memory B cells in peripheral blood, spleen and lymph nodes; however, B cells elimination in lymph nodes is not complete.27Egawa H. Ohmori K. Haga H. et al.B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation.Liver Transplant. 2007; 13: 579-588Crossref PubMed Scopus (90) Google Scholar,30Genberg H. Hansson A. Wernerson A. Wennberg L. Tydén G. Pharmacodynamics of rituximab in kidney allotransplantation.Am J Transplant. 2006; 6: 2418-2428Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar The use of Rituximab in ABOi LDLT has resulted in significant reduction in AMR episodes, and markedly improved graft survival.31Dahlgren U.S. Bennet W. ABO-incompatible liver transplantation–A review of the historical background and results.Int Rev Immunol. 2019; 38: 118-128Crossref PubMed Scopus (16) Google Scholar In a multicentre study conducted in Japan, absence of Rituximab prophylaxis was the only significant factor associated with AMR. Incidence of AMR in Rituximab and non-Rituximab group was 6% and 23%, respectively. Local infusion therapy, IVIG and splenectomy had no impact on AMR and overall survival.10Egawa H. Teramukai S. Haga H. et al.Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.Am J Transplant. 2014; 14: 102-114Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar,28Cheng C.-H. Lee C.-F. Wang Y.-C. et al.ABO-incompatible liver transplantation: state of art and future perspectives.Curr Pharmaceut Des. 2020; 26: 3406-3417Crossref PubMed Scopus (3) Google Scholar Table 1.Table 1Studies Showing ABOi LDLT Outcomes in Post- Rituximab Era.StudyLT typeNumber of patientsGraft survival ratesPatient survival ratesKim JM et al. 201877Kim J.M. Kwon C.H.D. Joh J.W. et al.ABO-Incompatible living donor liver transplantation with rituximab and total plasma exchange does not increase hepatocellular carcinoma recurrence.Transplantation. 2018; 102: 1695-1701Crossref PubMed Scopus (21) Google ScholarAdult ABOi LDLT591-, 2- and 3-years survival rates– 90.3%, 79.7% and 73.3%1-, 2- and 3-years survival rates– 90.6%, 85.0% and 81.9%Song et al. 20165Song G.W. Lee S.G. Hwang S. et al.ABO-incompatible adult living donor liver transplantation under the desensitization protocol with rituximab.Am J Transplant. 2016; 16: 157-170Abstract Full Text Full Text PDF PubMed Scopus (85) Google ScholarAdult ABOi LDLT2351, 3-years survival rates– 93.3% and 89.2%1, 3-years survival rates– 96.5% and 92.3%Kim SH et al. 201778Kim S.H. Lee E.C. Shim J.R. Park S.J. A simplified protocol using rituximab and immunoglobulin for ABO-incompatible low-titre living donor liver transplantation.Liver Int. 2018; 38: 932-939Crossref PubMed Scopus (21) Google ScholarAdult ABOi LDLT43NA3-years survival rate- 82.4%Lee CF et al. 201548Lee C.F. Cheng C.H. Wang Y.C. et al.Adult living donor liver transplantation across ABO-incompatibility.Medicine. 2015; 94e1796Google ScholarAdult ABOi LDLT461,3- and 5-years survival rates– 81.7%, 75.7% and 71.0%1,3- and 5-years survival rates– 81.7%, 75.7% and 71.0%Ikegami T et al. 201679Ikegami T. Yoshizumi T. Soejima Y. Uchiyama H. Shirabe K. Maehara Y. Feasible usage of ABO incompatible grafts in living donor liver transplantation.Hepatobiliary Surg Nutr. 2016; 5: 91PubMed Google ScholarAdult ABOi LDLT191- and 5-years survival rates– 94.7% and 87.9%NAHonda et al. 201880Honda M. Sugawara Y. Kadohisa M. et al.Long-term outcomes of ABO-incompatible pediatric living donor liver transplantation.Transplantation. 2018; 102: 1702-1709Crossref PubMed Scopus (38) Google ScholarPaediatric ABOi LDLT291,3- and 5-years survival rates −82.8%, 82.8%, 78.2%NAABOi, ABO incompatible; LDLT, Living donor liver transplant; NA, not available. Open table in a new tab ABOi, ABO incompatible; LDLT, Living donor liver transplant; NA, not available. Rituximab has also been used as a standalone desensitisation measure before transplant. In a small study of 40 patients, Yamamoto et al. showed similar survival and AMR rates between patients who received Rituximab with or without plasmapheresis (PP). Patients who did not receive PP had lower fungal and viral infection rates.32Yamamoto H. Uchida K. Kawabata S. et al.Feasibility of monotherapy by rituximab without additional desensitization in ABO-incompatible living-donor liver transplantation.Transplantation. 2018; 102: 97-104Crossref PubMed Scopus (19) Google Scholar Lee et al. compared ABOi LDLT outcomes in two groups who received single dose of Rituximab 2 weeks before transplant. Plasmapheresis was done only in one of the two groups. ABOi related complications and survival rates were similar in both groups. Authors concluded that Rituximab alone was sufficient to achieve desensitisation. ABO antibody titre at the time of LDLT for most of the patients was below 1:16.33Lee E.C. Kim S.H. Shim J.R. Park S.J. A comparison of desensitization methods: rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2018; 17: 119-125Crossref PubMed Scopus (19) Google Scholar Whether or not these Rituximab monotherapy protocols are applicable for the patients with high pre-operative titres need further evidences. Long-term biliary complications and graft survival data is also limited for these shorter regimes. The presence of preformed anti A and anti B isoagglutinin in recipients is responsible for AMR and related complications after transplant, and risk of these complications increase with higher agglutinins titres.6Oh J. Kim J.M. Immunologic strategies and outcomes in ABO-incompatible living donor liver transplantation.Clin Mol Hepatol. 2020; 26: 1-6Crossref PubMed Scopus (18) Google Scholar,20Egawa H. Oike F. Buhler L. et al.Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation.Transplantation. 2004; 77: 403-411Crossref PubMed Scopus (162) Google Scholar Plasmapheresis is an effective method to remove iso agglutinins and bring down the titres within acceptable limit. As plasmapheresis only removes the preformed antibodies without affecting the synthesis, titre may rise again, and patients usually require more than one session.34Kozaki K. Egawa H. Ueda M. et al.The role of apheresis therapy for ABO incompatible living donor liver transplantation: the Kyoto University experience.Ther Apher Dial. 2006; 10: 441-448Crossref PubMed Scopus (30) Google Scholar Pre-transplant target ABO isoagglutinin titre differs from centre to centre, and may varies from less than 1:8 to 1:64 in immediate pre-transplant period. As discussed earlier, those patients who have achieved the target titres with Rituximab administration may not need plasmapheresis.32Yamamoto H. Uchida K. Kawabata S. et al.Feasibility of monotherapy by rituximab without additional desensitization in ABO-incompatible living-donor liver transplantation.Transplantation. 2018; 102: 97-104Crossref PubMed Scopus (19) Google Scholar,33Lee E.C. Kim S.H. Shim J.R. Park S.J. A comparison of desensitization methods: rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2018; 17: 119-125Crossref PubMed Scopus (19) Google Scholar A single session of plasmapheresis usually result in 50–60% reduction in IgG and Ig M levels.19Kawagishi N. Satomi S. Current aspects of ABO-incompatible liver transplantation.Clin Case Rep Rev. 2016; https://doi.org/10.15761/ccrr.1000221Crossref Google Scholar,35Takahashi K. A new concept of accommodation in ABO-incompatible kidney transplantation.Clin Transplant. 2005; 19 (Supplement): 76-85Crossref PubMed Google Scholar A recipient may require more than one session to achieve the target isoagglutinin titres. Plasmapheresis involves exchange of large volume of patient plasma, along with removal of plasma proteins, immunoglobulins in addition to ABO antibodies. Side effects can include hypersensitivity, haemodynamic stress and citrate toxicity.36Song G.-W. ABO incompatability in liver transplantation.Hanyang Med Rev. 2014; 34: 202Crossref Google Scholar Plasmapheresis is also used to bring down post-liver transplant rebound of ABO isoagglutinins. Double filtration plasmapheresis is a variation of plasma exchange therapy, which contains separate system of plasma separator and fractionator. It effectively removes large proteins like immunoglobulins, but low molecular weight proteins like coagulation factors and albumin are transfused back to the recipients. In comparison to regular plasma exchange, in double filtration plasmapheresis requirement of replacement albumin and fresh frozen plasma is reduced. This method is mainly used in Asian countries, and experience is limited in other parts of the world.36Song G.-W. ABO incompatability in liver transplantation.Hanyang Med Rev. 2014; 34: 202Crossref Google Scholar,37Thalgahagoda S. Webb N.J.A. Roberts D. et al.Successful ABO incompatible renal transplantation following rituximab and DFPP after failed immunoadsorption.Pediatr Transplant. 2014; https://doi.org/10.1111/PETR.12227Crossref PubMed Google Scholar Immunoadsorption (IA) works in the same way as plasmapheresis by removing ABO isoagglutinins, however it differs from plasmapheresis as it removes only specific antibodies. Antigen specific columns of immunoadsorption adsorb ABO antibodies, and rest of immunoglobulins and plasma components are returned to recipients. Adverse effects profile of IA is relatively better than nonselective plasmapheresis.38de Weerd A.E. van Agteren M. Leebeek F.W. Ijzermans J.N.M. Weimar W. Betjes M.G.H. ABO-incompatible kidney transplant recipients have a higher bleeding risk after antigen-specific immunoadsorption.Transpl Int. 2015; 28: 25-33Crossref PubMed Scopus (36) Google Scholar Many studies in ABOi kidney transplantation have showed the efficacy of IA, however there is limited published data in liver transplant recipients.31Dahlgren U.S. Bennet W. ABO-incompatible liver transplantation–A review of the historical background and results.Int Rev Immunol. 2019; 38: 118-128Crossref PubMed Scopus (16) Google Scholar,39Genberg H. Kumlien G. Wennberg L. Tyden G. The efficacy of antigen-specific immunoadsorption and rebound of anti-A/B antibodies in ABO-incompatible kidney transplantation.Nephrol Dial Transplant. 2011; 26: 2394-2400Crossref PubMed Scopus (55) Google Scholar,40Makroo R.N. Agrawal S. Chowdhry M. Kakkar B. Thakur U.K. Efficacy of single, extended and goal directed immunoadsorption in ABO incompatible living related donor liver transplantation.Transfus Apher Sci. 2016; 55: 329-332Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Post-operative local infusion therapy (LIT) in portal vein using Gabexate mesylate, methylprednisolone or prostaglandin E1 has been used in the past. The use of LIT prevents microangiopathy by ameliorating the inflammatory response triggered by preformed antibodies and donor antigen interaction.15Egawa H. Challenge to ABO blood type barrier in living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2020; 19: 342-348Crossref PubMed Scopus (10) Google Scholar Their use has resulted in improved survival outcomes in liver transplant, and 2-year adult recipient survival in Japan increased from 60% to 80% in ABOi LDLT.14Tanabe M. Kawachi S. Obara H. et al.Current progress in ABO-incompatible liver transplantation.Eur J Clin Invest. 2010; 40: 943-949Crossref PubMed Scopus (87) Google Scholar,19Kawagishi N. Satomi S. Current aspects of ABO-incompatible liver transplantation.Clin Case Rep Rev. 2016; https://doi.org/10.15761/ccrr.1000221Crossref Google Scholar Infusion therapy is given through catheter insertion in portal vein or hepatic artery. Catheter related complications like bleeding, infection and thrombosis can be seen in 16% and 37% cases in hepatic artery and portal vein infusion therapy, respectively.41Egawa H. Teramukai S. Haga H. Tanabe M. Fukushima M. Shimazu M. Present status of ABO-incompatible living donor liver transplantation in Japan.Hepatology. 2008; 47: 143-152Crossref PubMed Scopus (181) Google Scholar With the introduction of Rituximab, LIT does not seem to have any additional advantage in the prevention of AMR or survival outcomes. Song et al. showed no difference in AMR incidence and survival outcomes in patients with or without LIT.42Kim J.M. Kwon C.H.D. Joh J.W. et al.ABO-incompatible living donor liver transplantation is suitable in patients without ABO-matched donor.J Hepatol. 2013; 59: 1215-1222Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar LIT also had high adverse events rate leading to discontinuation in many patients.5Song G.W. Lee S.G. Hwang S. et al.ABO-incompatible adult living donor liver transplantation under the desensitization protocol with rituximab.Am J Transplant. 2016; 16: 157-170Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar However, in case of emergency ABOi LDLT and DDLT when Rituximab may not lead to significant B cell depletion due to limited time, use of LIT can be considered.10Egawa H. Teramukai S. Haga H. et al.Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.Am J Transplant. 2014; 14: 102-114Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar,15Egawa H. Challenge to ABO blood type barrier in living donor liver transplantation.Hepatobiliary Pancreat Dis Int. 2020; 19: 342-348Crossref PubMed Scopus (10) Google Scholar,43Song G.W. Lee S.G. Hwang S. et al.Biliary stricture is the only concern in ABO-incompatible adult living donor liver transpla" @default.
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• W4313398545 date "2023-07-01" @default.
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• W4313398545 title "Strategies for ABO Incompatible Liver Transplantation" @default.
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• W4313398545 doi "https://doi.org/10.1016/j.jceh.2022.12.008" @default.
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