Chronic graft-versus-host disease of the liver: Presentation as an acute hepatitis

Chronic graft-versus-host disease (GVHD) of the liver usually presents as a n indolent cholestatic disease in patients with skin, mouth, and eye involv ement. We observed 14 patients in whom chronic GVHD of the liver presented with marked elevations of serum aminotransferases, clinically resembling ac ute viral hepatitis. Onset of liver dysfunction was at 294 days (range, 74- 747 days) after allogeneic hematopoietic cell transplantation and coincided with a recent cessation or taper of immunosuppressive drugs. Median peak s erum alanine transaminase (ALT) was 1,640 U/L (698-2,565 U/L), and median b ilirubin was 12.3 mg/dL (0.9-55.9 mg/dL). All biopsies showed characteristi c features of GVHD with damaged and degenerative small bile ducts. Other fe atures included a marked lobular hepatitis, moderate to marked amounts of h epatocyte unrest, sinusoidal inflammation with perivenular necroinflammator y foci, and many acidophilic bodies scattered throughout the lobule. When h igh-dose immunosuppressive therapy was instituted soon after presentation, progressive improvement and eventual normalization of liver enzymes and bil irubin levels were observed. However, in cases in which the diagnosis was n ot made and therapy was delayed, a progressive cholestatic picture emerged with histologic evidence of loss of small bile ducts and portal fibrosis, W e conclude that a distinct syndrome of chronic liver GVHD presenting as an acute hepatitis can be recognized in a patient at risk who is receiving no, or minimal, immunosuppressive medications. Liver biopsy is necessary to ex clude viral causes of liver dysfunction and to confirm characteristic abnor malities of small bile ducts. Institution of high-dose immunosuppression ca n prevent progressive bile duct destruction and effect resolution of jaundi ce if given early.