title: New protocol of immunosuppression for liver transplantation across ABO barrier: the use of Rituximab, hepatic arterial infusion, and preservation of spleen.
abstract: BACKGROUND
  An ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) is a challenge. Until 2000 systemic multidrug immunosuppression and splenectomy was the gold standard with poor results. Application of local administration with prostagrandin E1 (PGE1) and steroids via a portal vein (PV) catheter dramatically improved the survival from 20% to 60% but PV thrombus became a problem (35%). To solve it, an hepatic arterial (HA) catheter was used instead of a PV catheter and splenectomy was omitted. Although the PV thrombus problem was resolved, the ABO antibody titers significantly increased, and two cases of uncontrollable humoral rejection (HR) were experienced. In this study, Rituximab was introduced instead of splenectomy to decrease the antibody. We report the efficacy of prophylaxis with Rituximab for ABO-I LDLT.
  
  
  METHODS
  Eight patients received. Rituximab at 2 to 14 days before LDLT. During the operation, the spleen was preserved. Methylpredonisolone and PGE1 were administered via an HA catheter for 2 to 3 weeks after LDLT in addition to an immunosuppressive regimen consisting of tacrolimus and steroids. Antibody titers were measured serially.
  
  
  RESULTS
  There was no clinical HR. Two patients died of complications unrelated to HR. The antibody titer decreased compared to patients without splenectomy/rituximab. B cells (CD19) were depleted from peripheral blood for up to 3 months. Cytomegalovirus infections were decreased compared to patients with splenectomy (P = .085).
  
  
  CONCLUSIONS
  Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.
authors.affiliation: Kyoto University Graduate School of Medicine, Department of Transplantation and Immunology, Shougoin, Kyoto, Japan. ayoshi14@kuhp.kyoto-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: S
authors.initials: S
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: M
authors.initials: M
authors.lastname: Kasahara
authors.forename: K
authors.initials: K
authors.lastname: Uryuhara
authors.forename: F
authors.initials: F
authors.lastname: Oike
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Egawa
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001787:Blood Group Incompatibility; D004334:Drug Administration Schedule; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods*; D007261:Infusions, Intra-Arterial; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011169:Portal Vein; D011300:Preoperative Care; D000069283:Rituximab; D013154:Spleen / Q000502:physiology*
chemical_list: D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab