CHOLESTATIC DISEASES AND MECHANISMS OF CHOLESTASIS

Primary biliary cirrhosis and primary sclerosing cholangitis are disti nct hepatobiliary disorders that are both characterized by bile duct i njury, 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 c hoice. The association of primary biliary cirrhosis with HLA-DR8 was c onfirmed, the involvement of both activated B- as well as T-cell popul ations has been documented, and the T-cell response to the pyruvate de hydrogenase complex has been shown to be blocked by antibodies to HLA class II antigens. B cells were found in significant numbers within th e portal tracts of affected livers, and were shown to be maximally sti mulated to produce specific antimitochondrial antibodies. It was propo sed that antigen recognition may be triggered through a process involv ing immunoglobulin A secretion into bile, whereas another report confi rmed significant cross-reactivity with bacterial antigens. Research in to the mechanism of action of ursodeoxycholic acid demonstrated a dire ct cytoprotective effect against toxic bile acids, as well as effects on interleukin-2 production and on bile acid pools. In primary scleros ing cholangitis, the role of neutrophil cytoplasmic antibodies was fur ther evaluated, and the benefits and timing of liver transplantation w ere analyzed. Other cholestatic disorders investigated include drug-in duced jaundice, cholestasis of pregnancy, cystic fibrosis, and Caroli' s disease, as well as the role of ursodeoxycholic acid and other thera peutic modalities.