Autoimmune diseases of the liver
Apr 20, 2018
Autoimmune mechanisms play an important role in the pathogenesis of a number of liver diseases: chronic active hepatitis, chronic autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune cholangitis. An important sign of the impaired state of immunity in chronic active liver diseases is the appearance in the blood of autoantibodies that react with various antigenic components of cells and tissues.
Autoimmune chronic hepatitis( a variant of chronic active hepatitis) is a heterogeneous group of progressive inflammatory liver diseases. The syndrome of autoimmune chronic hepatitis is characterized by clinical symptoms of liver inflammation that last more than 6 months, and histological changes( necrosis and infiltrates of portal fields).For autoimmune chronic hepatitis, the following features are characteristic.
■ The disease is observed predominantly in young women( 85% of all cases).
■ Changes in the results of traditional laboratory indicators are manifested in the form of accelerated ESR, moderately expressed leukopenia and thrombocytopenia, mixed genesis anemia - hemolytic( positive direct Coombs test) and redistribution;
■ Changes in hepatic test results( bilirubin increased 2-10 times, transaminase activity 5-10 times or more, deitis ratios less than 1, alkaline phosphate activity increased slightly or moderately, increased AFP concentration, correlatingwith biochemical activity of the disease) /
■ Hypergammaglobulinemia in excess of normal 2 times or more( usually polyclonal with a predominant increase in IgG).
■ Negative test results for serological markers of viral hepatitis.
■ Negative or low AT titer to mitochondria.
To autoimmune diseases of the liver, primary biliary cirrhosis, which manifests itself in the form of a low-symptomatic chronic destructive, non-venous cholangitis, also results in the formation of cirrhosis. If before the primary biliary cirrhosis was considered as a rare disease, at present its prevalence has become very significant. The increase in the diagnosis of primary biliary cirrhosis is due to the introduction of modern laboratory research methods into clinical practice. The most characteristic for primary biliary cirrhosis is an increase in the activity of alkaline phosphatase, usually more than 3 times( in some patients it can be within the norm or slightly increased) and GGTP.The activity of alkaline phosphatase has no prognostic significance, but its reduction reflects a positive response to treatment. The activity of AST and ALT is moderately elevated( transaminase activity, 5-6 times higher than normal, is not characteristic of primary biliary cirrhosis).
Primary sclerosing cholangitis is a chronic cholestatic disease of the liver of unknown etiology, characterized by a nasal destructive inflammation, obliterating sclerosis and segmental dilatation of intra- and extrahepatic bile ducts, leading to the development of biliary cirrhosis, portal hypertension and liver failure. Primary sclerosing cholangitis is characterized by a stable syndrome of cholestasis( usually no less than twofold increase in the level of alkaline phosphatase), the level of transaminases in the blood is increased in 90% of patients( no more than 5 times).The concept of primary sclerosing cholangitis, as an autoimmune disease with genetic predisposition, is based on the identification of family cases, combination with other autoimmune diseases( most often with ulcerative colitis), disorders in cellular and humoral immunity, detection of autoantibodies( antinuclear, smooth muscle, cytoplasm of neutrophils).
Autoimmune cholangitis is a chronic cholestatic liver disease caused by immunosuppression. The histological picture of liver tissue in this disease is almost identical to the primary biliary cirrhosis, and the AT spectrum includes elevated titres of antinuclear and antimitochondrial AT.Autoimmune cholangitis,
does not appear to be a variant of the primary sclerosing cholangitis( Henry J. B., 1996).
The presence of antinuclear antibodies in patients with chronic autoimmune hepatitis is one of the main indicators that make it possible to distinguish this disease from prolonged viral hepatitis. These antibodies are detected in 50-70% of cases of active chronic( autoimmune) hepatitis and in 40-45% of cases of primary biliary cirrhosis. At the same time, in low titers, anti-nuclear antibodies can occur in practically healthy people, and their titer increases with age. They may appear after taking some drugs, such as procainamide, methyldopa, certain anti-tuberculosis and psychotropic drugs. Very often, the titer of anti-nuclear antibodies increases in healthy women during pregnancy.
Diagnostic tests have been developed to confirm the autoimmune nature of liver damage and differential diagnostics of various forms of autoimmune hepatitis and primary biliary cirrhosis, which allow to determine antimitochondrial AT( AMA), AT to smooth muscle, AT to hepatic-specific lipoprotein and Ar liver of liver, AT to microsomalAg liver and kidney, AT to neutrophils, etc.