Although the concurrent presence of the characteristic rash provides suggestive clinical evidence, biopsy is the most definitive method to diagnose GVHD of the liver. However, this may not be feasible because of the possibility of acute bleeding due to severe thrombocytopenia soon after HCT. A transjugular hepatic biopsy may be preferred if an adequate amount of tissue can be obtained. The primary histologic finding is extensive bile duct damage (eg, bile duct atypia and degeneration, epithelial cell dropout, lymphocytic infiltration of small bile ducts), leading to occasionally severe cholestasis [ 26,31-33 ].
In a phase II clinical trial, Martinez et al (2009) examined the safety and effectiveness of alemtuzumab in treating steroid-refractory acute GVHD (aGVHD) grade II or higher after stem cell transplantation. A total of 10 adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with CR and 3 with partial response. Eight infectious events (4 of grade 3 to 4) and 7 CMV re-activations were observed. Six patients had grade 3 to 4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range of 4 to 88 days) after alemtuzumab treatment. Overall, these findings suggested that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.