Bile Duct Apoptosis and Cholestasis Resembling Acute Graft-Versus-Host Disease After Autologous Hematopoietic Cell Transplantation

Gastroenterology/Hepatology, Fred Hutchinson Cancer Research Center, Puget Sound Veterans Affairs Medical Center, and the University of Washington School of Medicine, Seattle 98109-1024, USA.
American Journal of Surgical Pathology (Impact Factor: 5.15). 08/2000; 24(7):1004-8. DOI: 10.1097/00000478-200007000-00012
Source: PubMed


Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation.
We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease.
Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD.
Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.

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    • "Although there is no genetic disparity in GVHD development among patients undergoing ASCT, auto-GVHD has been reported to arise either spontaneously (2-5) or in patients receiving immunologic modulation (6,7). Auto-GVHD is generally self-limited and often requires no treatment (8-10). In contrast, several case reports have described patients presenting with severe and ultimately fatal spontaneous auto-GVHD (2-4). "
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