PRIMARY BILIARY-CIRRHOSIS - IMMUNOPATHOGENESIS AND OPTIMUM MANAGEMENT

Primary biliary cirrhosis is a well-characterised disorder of autoimmu ne origin whose exact pathogenesis remains poorly understood. Populati on studies have suggested an association with human leucocyte antigen (HLA)-DR8, and patients are universally positive for antimitochondrial antibodies; however, the clinical relevance of these observations is unclear, Other putative autoantigens have been proposed, Numerous abno rmalities throughout the immune system as well as in complement pathwa ys have been characterised, and major histocompatibility complex (MHC) expression on biliary epithelial cells is increased, Consequently, dr ugs whose actions are primarily immunomodulatory have undergone testin g in the therapy of primary biliary cirrhosis, but none have demonstra ted particular promise. Ursodeoxycholic acid remains the therapy of ch oice, and it is believed to exert its beneficial effects by modifying bile salt pool content and kinetics, as well as possibly through immun ological mechanisms, Improvement in biochemical and clinical parameter s with ursodeoxycholic acid therapy is well recognised, and it also ap pears to improve hepatic histology and retard progression Co transplan tation or death, Antifibrotic therapy with colchicine has shown some p romise in small studies; however, the results of larger clinical trial s designed to examine its role in conjunction with ursodeoxycholic aci d are not yet available, Liver transplantation is the established trea tment for end-stage primary biliary cirrhosis, and recurrent disease i n the allograft has not been satisfactorily documented.