Current problems in primary biliary cirrhosis.
Journal - Zeitschrift für Gastroenterologie (GERMANY )
Despite the many advances made in the field of PBC, the central questions of this enigmatic disease remain unanswered. The pathogenesis is uncertain and there is no effective therapy. Of the various aetiologies proposed for the disease none has really withstood the test of time: if the disease were truly auto-immune, it might be anticipated that there would be a clear-cut response to cortico-steroid therapy: although such treatment has a slight effect on improving liver chemistry, compared with other auto-immune diseases such as auto-immune chronic active hepatitis. Steroids are relatively ineffective. An infectious aetiology has been suggested but no organism has been reliably isolated or implicated in the disease. Attempts at treatment have been largely hindered by the long natural history and the uncertainty as to choosing appropriate endpoints for studies. Perhaps the most intriguing observation has been the association with the anti-mitochondrial antibodies. While the antigens have been identified, these are ubiquitous enzymes locate within the mitochondrion. How antibodies to such antigens are involved in the pathogenesis remains uncertain although our recent demonstrations that some antigens may be present on the surface of biliary epithelial cells may answer the question. However, further work may be required to confirm these findings and then to determine the reasons why there is such abnormal antigen expression in the disease.
|ISSN : ||0044-2771|
|Mesh Heading : ||Adrenal Cortex Hormones Autoantibodies Epithelium Humans Liver Liver Cirrhosis, Biliary Liver Function Tests Liver Transplantation Microsomes, Liver Treatment Outcome therapeutic use blood immunology immunology drug therapy immunology immunology immunology|
|Mesh Heading Relevant : ||etiology|
Immune mechanisms in tienilic acid associated hepatotoxicity.
Journal - Gut (ENGLAND )
In order to investigate the mechanisms underlying the hepatotoxicity associated with tienilic acid (Ticrynafen) ingestion we have looked for evidence of sensitisation to drug altered liver cell determinants using an indirect antibody dependent, cell mediated cytotoxicity assay (ADCC). As targets, hepatocytes were isolated from rabbits pretreated with either tienilic acid or its isomer with or without previous enzyme induction with either phenobarbitone or B-naphthoflavone (BNF). Sera from 16 of 36 patients with presumed tienilic acid hepatotoxicity induced significant cytotoxicity to hepatocytes isolated from rabbits pretreated with BNF and subsequently tienilic acid. Three of 10 sera from patients receiving tienilic acid but without overt liver damage also induced significant cytotoxicity to these hepatocytes, however, although none of 20 normal controls or of 16 patients with other liver diseases did so. Non-organ specific autoantibodies, classified as anti-LKM2, were also detectable. These were present in association with tienilic acid associated antibodies: of the 36 patients with presumed tienilic acid hepatotoxicity, 38% had both antibodies, 18% had only anti-LKM2 antibodies and 9% only tienilic acid associated antibodies. These results suggest that this drug reaction is associated with sensitisation to drug altered liver cell antigens and autoantigens. If ticrynafen associated hepatotoxicity is immune mediated, then one possible mechanism is that the drug induced antigens break tolerance, leading to an immune attack on normal liver cell components.
|ISSN : ||0017-5749|
|Mesh Heading : ||Adult Aged Aged, 80 and over Female Glycolates Hepatitis, Toxic Humans Male Middle Aged Ticrynafen etiology adverse effects|
|Mesh Heading Relevant : ||Antibody-Dependent Cell Cytotoxicity immunology immunology immunology|