Old and new immunosuppressant drugs: mechanisms and potential value

Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that predominantly affects women. It is characterized by inflammatory destruction of interlobular and septal bile ducts, periportal hepatitis, septal fibrosis and ultimately biliary cirrhosis1,2. The fundamental histopathologic lesion of the intrahepatic bile ducts in PBC is non-suppurative destructive cholangitis (NSDC) which is characterized by T cell infiltration of the biliary epithelia, resulting in segmental apoptosis of biliary epithelial cells and destruction of the bile duct1–3. Portal inflammatory infiltrates are predominantly composed of CD4 and CD8 T cells, and the CD4 T cells express a T helper 1 phenotype4. The observation that NSDC of interlobular and septal bile ducts also occurs in alloimmune-mediated conditions of hepatic allograft rejection and chronic graft-versus-host disease provides circumstantial support for the hypothesis that NSDC in PBC is mediated by autoimmune mechanisms1,2. Indeed, PBC has been considered a model autoimmune disease.