Immune disorders of the liver and bile duct

Gastroenterol Clin North Am. 1992 Jun;21(2):427-49.


Several hepatobiliary diseases appear to be mediated by the host immune response. They can be subdivided into those in which the immune reaction is against an infectious agent such as hepatitis viruses, those in which the immune reaction appears to be against an autoantigen expressed on hepatobiliary cells, and those due to alloimmunity. The existence of autoimmune liver diseases indicates a breakdown in the mechanisms responsible for self-tolerance. In HBV infection, the hepatocellular necrosis appears to be mediated by the host immune response against viral antigens expressed on the membranes of infected hepatocytes. Autoimmune chronic active hepatitis can be subdivided on the basis of differences in circulating autoantibodies. In classic type I autoimmune chronic hepatitis, autoantibodies are directed against non-organ- and non-species-specific antigens. Thus, they are unlikely to be involved in pathogenesis. In contrast, type II autoimmune chronic hepatitis is characterized by antibodies against specific cytochrome P-450 isoenzymes that appear to be expressed on the surface membrane of hepatocytes. Immunogenic cytochrome P-450 also can be induced by drug metabolism and haptenation. This indicates that environmental or medicinal xenobiotics may initiate autoimmune liver damage. Primary biliary cirrhosis is characterized by T-cell-mediated inflammation and destruction of interlobular and septal bile ducts and antibodies specific for epitopes of the 2-oxo-acid dehydrogenase multienzyme complex of mitochondria. The histopathologic lesion NSDC also is observed in alloimmune-mediated diseases such as CGVHD and rejection of liver allografts. PSC may be mediated by an immune response against endothelial cells of the peribiliary capillary plexus, with secondary reactions to bile duct epithelial cell antigens. The pathogenesis of alcoholic liver disease is multifactorial, but one component involves an immune response to acetaldehyde-protein adducts. Secondary sensitization of cell-mediated effector mechanisms, endothelial damage, and secretion of noxious cytokines appear to be involved in pathogenesis.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / immunology*
  • Bile Duct Diseases / immunology*
  • Cholangitis, Sclerosing / immunology
  • Chronic Disease
  • Graft Rejection / immunology
  • Graft vs Host Disease / immunology
  • Hepatitis / immunology
  • Hepatitis, Viral, Human / immunology
  • Humans
  • Liver Cirrhosis, Biliary / immunology
  • Liver Diseases / immunology*
  • Liver Diseases, Alcoholic / immunology
  • Liver Transplantation / immunology
  • Major Histocompatibility Complex / immunology
  • T-Lymphocyte Subsets / immunology