Primary biliary cirrhosis and primary sclerosing cholangitis are distinct hepatobiliary disorders that are both characterized by bile duct injury, the development of cirrhosis, and, in many cases, liver failure, often necessitating transplantation. Research continues to focus on the pathogenesis of these disorders and on the efficacy and mechanism of action of ursodeoxycholic acid, which currently is the therapy of choice. The association of primary biliary cirrhosis with HLA-DR8 was confirmed, the involvement of both activated B-as well as T-cell populations has been documented, and the T-cell response to the pyruvate dehydrogenase complex has been shown to be blocked by antibodies to HLA class II antigens. B cells were found in significant numbers within the portal tracts of affected livers, and were shown to be maximally stimulated to produce specific antimitochondrial antibodies. It was proposed that antigen recognition may be triggered through a process involving immunoglobulin A secretion into bile, whereas another report confirmed significant cross-reactivity with bacterial antigens. Research into the mechanism of action of ursodeoxycholic acid demonstrated a direct cytoprotective effect against toxic bile acids, as well as effects on interleukin-2 production and on bile acid pools. In primary sclerosing cholangitis, the role of neutrophil cytoplasmic antibodies was further evaluated, and the benefits and timing of liver transplantation were analyzed. Other cholestatic disorders investigated include drug-induced jaundice, cholestasis of pregnancy, cystic fibrosis, and Caroli's disease, as well as the role of ursodeoxycholic acid and other therapeutic modalities.
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