Bile duct injury as a part of diagnostic criteria for liver allograft rejection.

The decisive criterium of acute liver allograft rejection was found to be the presence of the diagnostic triad of acute rejection; ie, the presence of portal inflammatory mixed infiltrates, venous endothelialitis (both portal and central), and bile duct injury. On the basis of the presence of each of the components of the diagnostic triad, criteria for the diagnosis of different degrees of acute rejection were developed, particularly focusing attention on a detailed analysis of bile duct injury. Bile duct injury was shown to be an essential part of the histopathologic changes in all grades of acute rejection in the liver allograft, the grade of severity of bile duct injury correlating to a certain extent with the grade of severity of acute rejection. Our analyses have made it evident that bile duct injury, which most probably occurs earlier in the process of acute rejection than endothelialitis, is a more sensitive parameter than endothelialitis in the diagnosis of acute rejection. Furthermore, our analyses have revealed that bile duct injury in acute rejection is likely to be an irreversible process, depending on the number of episodes of acute rejection that previously occurred. On the other hand, it has become clear from our results that bile duct injury must not be considered to be an absolute histopathologic marker of acute rejection; however, it does have to be judged synoptically in connection with the other components of the diagnostic triad and the changes that the triad cause in the hepatic parenchyma. Additional analyses of the grade of severity of cholostases have shown that the cholostases are, to a certain degree, an accompanying phenomenon of the histopathologic changes characterizing acute rejection rather than a histopathologic change that is as significant as the presence of the components of the diagnostic triad.