In Western countries, the indication for liver transplantation using ABO-incompatible (ABO-I) donors remains controversial. The risks of ABO-I transplantation include antibody-mediated hyperacute rejection, a higher incidence of severe acute rejection, hepatic artery thrombosis, and biliary complications.1-3 Subsequently, the results of adult deceased donor liver transplantation using ABO-I grafts are poor, with an approximately 20% chance of 5-year graft survival.4 Histologically, the liver grafts are complicated by widespread hemorrhagic necrosis with intraorgan thrombosis and prominent arterial deposition of antibody and complement. Demetris et al.3 termed this syndrome “single-organ disseminated intravascular coagulation.” Prophylactic antilymphocyte globulin, plasmapheresis, splenectomy, soluble antigen, and ABO immunoadsorbents have been used with varying degrees of success but might be associated with a higher incidence of sepsis and do not improve the outcome for adult patients.5, 6 It has been concluded, therefore, that the use of ABO-I liver grafts is justified only in limited situations, such as in emergencies. ABO-I, ABO-incompatible; LDLT, living donor liver transplantation. It is another story, however, in Eastern countries, where the availability of deceased donor organs falls short of the population need and living donor liver transplantation (LDLT) is almost the only procedure that offers hope to patients with end-stage liver disease. All donors must be related to the patients; most of them are within three degrees of consanguinity or a spouse. If the patients have no ABO-identical or -compatible donors, ABO-I donors are the only available option. According to the Japanese Registry of Living Donor Liver Transplantation across ABO Blood Type Barrier, 97 ABO-I LDLTs were performed in Japan before March 2005; this corresponds to approximately 5% of the total adult (≥16 years of age) LDLTs performed. The 5-year survival rate of the patients was 38% before 2001 and improved to 63% among patients who underwent ABO-I after 2002. Some Japanese transplant surgeons7, 8 commented that the improvement was provided by innovative postoperative portal vein infusion therapy. The main purpose of this therapy is to control any local disseminated intravascular coagulation arising in ABO-I grafts. Three agents, methylprednisolone, prostaglandin E1, and gabexate mesylate, are infused continuously for 3 weeks after transplantation through a catheter placed in the portal vein during surgery. Prostaglandin E1 improves hepatic blood flow and microcirculation through its vasodilating effects and inhibits platelet/leukocyte adhesion. Gabexate mesylate is a serine protease inhibitor that inhibits thrombin, Xa, and platelet aggregation. These agents are logical choices for controlling local disseminated intravascular coagulation and immune responses. Systemic anti-rejection therapy basically follows the kidney protocol: pre- and postoperative plasmapheresis, splenectomy, and triple-immune prophylaxis, including steroids, tacrolimus, and antiproliferative agents. Recent advances in immunomodulatory therapy for ABO-I grafts include the use of anti-CD20 monoclonal antibody or soluble complement receptor9 as an alternative to splenectomy for B-cell depletion. More recently, the Kyoto group10 began infusing the two agents (methylprednisolone and prostaglandin E1) through a hepatic artery instead of the portal vein. They emphasized better graft survival with a reduced risk of portal vein thrombosis. The protocol described by Troisi et al.11 for an ABO-I barrier in this issue of Liver Transplantation is partly new but not entirely unexpected. Immunoadsorption with immobilized blood antigen A or B is used for ABO-I living donor kidney transplantation.12 The use of daclizumab instead of cyclophosphamide has been tried in ABO-I deceased donor liver transplantation.13 Of note is that this article11 is the first report from a Western country on ABO-I LDLT for an adult patient series. The report is very encouraging although the number is small and the follow-up period is short. We agree with the conclusions of the authors that the protocol deserves further application with immunologic studies. ABO-I liver grafting in adults may no longer be considered experimental but should be considered as a reasonable clinical option when no blood group–compatible liver is available for a critically ill patient. At the same time, however, liver transplantation using live ABO-I grafts should be a rare event. In LDLT, the physical and psychologic sacrifice by the donor is significant and is associated with high expectations of a good outcome for themselves and the recipient.14 The precise indication requires further debate in the Western countries where cadaveric organ is available, as the authors commented in the Discussion. The authors thank Dr. Hiroto Egawa (Kyoto University) for ABO-I LDLT data in Japan and Dr. Sumihito Tamura (University of Tokyo) for critical review of the article.