Severe veno-occlusive disease/sinusoidal obstruction syndrome after deceased-donor and living-donor liver transplantation

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.