Correlation of conventional histology, clinical outcomes, and C4d immunostaining in ABO-incompatible liver transplantation

In ABO blood type-incompatible liver transplantation (ABO-I LT), acute humoral rejection triggered by antibodies against donor-type isoagglutinins is the most serious form of rejection and often associated with graft loss. Typical histology of humoral rejection is recognized by biopsies taken at the onset of elevation of alloantibody titers; such biopsies reveal marked portal edema with or without hemorrhagic necrosis. Edema disappears several days after the onset of humoral rejection, and follow-up biopsies reveal relatively nonspecific findings such as hepatocyte necrosis or cholangitis-like portal fibrosis. In our series enrolled between 1995 and 2004, hemorrhagic portal edema was recognized in 17 of 114 (15%) patients who underwent primary ABO-I LT. All 17 patients showed elevation of anti-donor A/B IgM antibody titers (1:64 or higher), and 6-month graft survival was 59%. Deposition of C4d in portal stroma was demonstrated in 11 of 12 (92%) patients with hemorrhagic portal edema and some patients with other histology showing high postoperative alloantibody titers. Although more study is needed, these results suggest that C4d immunostaining can be a useful marker to demonstrate humoral rejection in ABO-I LT.