Yoshizawa A, Sakamoto S, Ogawa K, Kasahara M, Uryuhara K, Oike F, Ueda M, Takada Y, Egawa H, Tanaka K
Kyoto University Graduate School of Medicine, Department of Transplantation and Immunology, Shougoin, Kyoto, Japan.
Transplant Proc. 2005 May;37(4):1718-9. doi: 10.1016/j.transproceed.2005.03.148.
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.
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.
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).
Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.
ABO血型不相容（ABO-I）活体供肝肝移植（LDLT）是一项挑战。直到2000年，全身多药免疫抑制和脾切除术一直是金标准，但效果不佳。通过门静脉（PV）导管局部应用前列腺素E1（PGE1）和类固醇显著提高了生存率，从20%提高到60%，但PV血栓成为一个问题（35%）。为了解决这个问题，使用肝动脉（HA）导管代替PV导管，并省略了脾切除术。虽然PV血栓问题得到了解决，但ABO抗体滴度显著增加，并且出现了两例无法控制的体液排斥反应（HR）。在本研究中，引入利妥昔单抗代替脾切除术以降低抗体水平。我们报告利妥昔单抗预防ABO-I LDLT的疗效。
8例患者在LDLT前2至14天接受利妥昔单抗治疗。手术过程中保留脾脏。除了由他克莫司和类固醇组成的免疫抑制方案外，LDLT后通过HA导管给予甲泼尼龙和PGE1 2至3周。连续测量抗体滴度。
未出现临床HR。两名患者死于与HR无关的并发症。与未进行脾切除术/利妥昔单抗治疗的患者相比，抗体滴度降低。外周血中的B细胞（CD19）在长达3个月的时间内减少。与脾切除患者相比，巨细胞病毒感染减少（P = 0.085）。
利妥昔单抗预防和HA输注疗法可预防临床HR，这可能为克服肝移植中的ABO血型屏障提供突破。
