Posttransplant immune-mediated cholangiopathies

Liver transplantation (LT) is the treatment of end-stage chronic liver diseases, mainly decompensated cirrhosis and hepatocellular carcinoma. Biliary complications can be schematically classified into macroscopic versus microscopic lesions. Immune-related cholangiopathies include rejection, graft-versus-host disease (GVHD) and recurrence of pre-LT auto-immune biliary diseases, i.e. primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Here, we review the various types of posttransplant immune-related cholangiopathies, and discuss their clinical implications, especially diagnostic issues.

Recurrence of PBC and PSC after LT is increasingly well described in large cohorts and long-term follow-up. In this setting, the preventive effect of ursodeoxycholic acid on PBC recurrence, as well as the deleterious role of tacrolimus are now well documented. In addition, the significant negative impact of recurrent PBC on survival after LT has recently been demonstrated. With respect to rejection-associated biliary injury, a growing body of evidence is emerging on the role of anti-HLA antibody-mediated rejection.

Immune-mediated cholangiopathies occurring after LT can be divided in two main nosologic groups: biliary lesions due to recurrence of PBC or PSC, or in the context of rejection, either acute or chronic, T-cell- or antibody-mediated. GVHD is very rare. Final diagnosis is strongly based on clinical context (indication for LT, delay since transplantation, biological abnormalities, imaging) but also and to an even greater extent on biopsy of liver graft. Clinico-pathological discussions are recommended, hearing in mind that diseases can be intertwined.