Apoptotic hepatocytes in rejection and vascular occlusion in liver allograft specimens

Abstract

Aims: Programmed cell death (apoptosis) has been described in different hepatobiliary diseases and in immune-mediated cytotoxicity. Apoptosis of hepatocytes and bile duct epithelial cells was detected in chronic liver allograft rejection. In severe acute rejection a DNA fragmentation in-situ assay showed positivity of apoptotic cells and centrilobular necrosis. Although apoptosis is triggered by ischaemia, the potential role of apoptosis in tissue damage caused by hepatic vascular occlusion after orthotopic liver transplantation has not yet been investigated.

Methods and results: We examined biopsies for apoptotic cell death in 50 liver allografts: 29 with acute liver rejection, six without rejection, five time-zero biopsies, and 10 cases with hepatic artery thrombosis. In addition to a semiquantitative assessment of apoptotic bodies in haematoxylin and eosin stains, an in-situ end nick-labelling technique (TUNEL) was used to detect DNA fragmentation. In all cases with hepatic artery thrombosis the incidence of apoptosis was found significantly increased in comparison to acute rejection.

Conclusions: As apoptosis is a mechanism in the early stages of tissue damage prior to necrosis, increased apoptosis in liver allograft biopsies might be regarded as a signal of early ischaemia indicating initial vascular occlusion.