Pathogenesis and treatment of bile duct loss after liver transplantation

The bile duct is one of the main targets of immune reaction after liver transplantation. Bile duct loss, termed ductopenia or vanishing bile duct syndrome, is a typical pathological finding of chronic rejection (CR). The mechanism of bile duct loss in allograft rejection is twofold: T-cell mediated cytotoxicity and ischemic sequelae caused by obliterative arteriopathy. Whether or not CR is reversible remains controversial. Accumulating data show the reversibility of bile duct injury caused by immunoreaction, but not the reversibility of injuries caused by ischemia. In our living-related liver transplantation program at Kyoto University Hospital, the incidence of ductopenia, which indicates the incidence of CR, was 14 of 423 patients (3.3%), comparable to the result for cadaveric liver transplantation. The onset was within 1 year, except in 2 patients. Of the 14 patients with ductopenia, 2 recovered without re-transplantation, and of the remaining 12 patients, 7 underwent re-transplantation, and the other 5 died without a chance of re-transplantation. The diagnosis of ductopenia was based on the pathological findings, which specify that more than 50% of the portal triad does not contain visible bile ducts. Recently, staging criteria of CR were proposed by an international panel, who recommended splitting CR into an early stage and a late stage. At present, no specific immunosuppressive regimen for CR has been developed; however, early diagnosis based on these new criteria, and the earlier implementation of enforced immunosuppression, with conventional drugs, may be beneficial for a further reduction in CR.