“Silent” presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection

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Abstract
Hemorrhagic centrilobular necrosis and fibrous stenosis of hepatic venules, suggesting veno-occlusive disease (VOD) have rarely been observed after orthotopic liver transplantation (OLT). The aim of this study was to determine the prevalence of this syndrome after OLT in relation to the course with particular reference to acute rejection and to azathioprine administration. VOD was identified in 19 of 1,023 patients transplanted over a 9-year period. VOD occurred at a median of 30 days posttransplantation, without clear cut clinical evidence for hepatic vein outlet obstruction. Seventeen of the 19 patients had an episode of acute rejection before or at the time of VOD. These episodes were compared with that of patients without VOD. In patients with VOD, portal inflammation and endothelialitis were enhanced (P = .014 and P = .048) and endothelialitis was also higher than bile duct damage (P = .03). The incidence of a centrilobular endothelialitis for both groups was not different although an increased trend was observed in the study group (64% vs. 46%; P = .18). The incidence of persistent rejection was similar between both groups (47% vs. 41%). The incidence of chronic rejection was higher in the study group (29% vs. 10%; P = .04). All patients with VOD received azathioprine as part of immunosuppressive regimen. Despite azathioprine withdrawal, zone 3 changes persisted in 57% of patients. In conclusion, the incidence of VOD was 1.9% after OLT. The association of prominent endothelial involvement and VOD with acute rejection in most cases suggests an immunological phenomenon.