APOPTOSIS IN THE HUMAN LIVER DURING ALLOGRAFT-REJECTION AND END-STAGELIVER-DISEASE

The contribution of apoptosis (programmed cell death) to cellular dama ge in human liver disease is unknown. Using the in situ DNA end labell ing method (ISEL), evidence was sought of programmed cell death (PCD) in liver tissue from patients with various liver diseases. In particul ar, the study aimed to determine whether PCD is involved in either the loss of interlobular bile ducts (vanishing bile duct syndrome-VBDS) o r the perivenular hepatocyte drop-out, both of which are characteristi c of irreversible graft rejection. Large numbers of apoptotic hepatocy tes were found in perivenular areas in tissues taken from patients wit h chronic graft rejection. Significant hepatocyte apoptosis, was not s een in long-term stable allografts, primary biliary cirrhosis, cholest asis, paracetamol-induced fulminant hepatic failure, or fulminant hepa tic failure of indeterminate origin (non-A, non-B, non-C hepatitis). B ile ducts rarely stained positively, but mononuclear cells present in the post-transplant tissues were frequently positive, showing nuclear or cytoplasmic staining. The presence of cytoplasmic staining suggeste d that some mononuclear cells had ingested apoptotic DNA from other ce llular sources. PCD may thus contribute to the perivenular hepatocyte loss in chronic rejection. The absence of ductular epithelial cell sta ining suggests that PCD is not involved significantly in the bile duct loss of VBDS. Furthermore, apoptosis of mononuclear cells implies tha t PCD may be involved in regulating the inflammatory cell infiltration of graft rejection.