Diagnosis of autoimmune liver diseases

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 impaired immunity in chronic active liver diseases is the appearance of autoantibodies in the blood 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 lasting more than 6 months and histological changes (necrosis and infiltrates of portal fields). The following features are characteristic of autoimmune chronic hepatitis.

• The disease is observed mainly in young women (85% of all cases).
• Changes in the results of traditional laboratory parameters are manifested in the form of an accelerated ESR, moderate leukopenia and thrombocytopenia, anemia of mixed genesis - hemolytic (positive direct Coombs test) and redistribution;
• Changes in liver function tests characteristic of hepatitis (bilirubin increased by 2-10 times, transaminase activity by 5-10 times or more, de Ritis coefficient less than 1, alkaline phosphatase activity increased slightly or moderately, increased AFP concentration, correlating with the biochemical activity of the disease).
• Hypergammaglobulinemia with a level exceeding the norm by 2 times or more (usually polyclonal with a predominant increase in IgG).
• Negative results of the study for serological markers of viral hepatitis.
• Negative or low titer of antibodies to mitochondria.

Primary biliary cirrhosis, which manifests itself as low-symptom chronic destructive non-purulent cholangitis, which ends with the formation of cirrhosis, is also an autoimmune liver disease. If previously primary biliary cirrhosis was considered a rare disease, now its prevalence has become quite significant. The increased frequency of diagnosis of primary biliary cirrhosis is explained by the introduction of modern laboratory research methods into clinical practice. The most characteristic feature of primary biliary cirrhosis is an increase in the activity of alkaline phosphatase, usually more than 3 times (in some patients it may be within the normal range or slightly increased) and GGT. Alkaline phosphatase activity has no prognostic value, but its decrease reflects a positive response to treatment. AST and ALT activity are moderately increased (transaminase activity, 5-6 times higher than normal, is not characteristic of primary biliary cirrhosis).

Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown etiology, characterized by non-purulent destructive inflammation, obliterating sclerosis and segmental dilation of the intra- and extrahepatic bile ducts, leading to the development of biliary cirrhosis, portal hypertension and liver failure. Primary sclerosing cholangitis is characterized by stable cholestasis syndrome (usually at least a twofold increase in the alkaline phosphatase level), the level of transaminases in the blood is elevated in 90% of patients (no more than 5 times). The concept of primary sclerosing cholangitis as an autoimmune disease with a genetic predisposition is based on the identification of familial cases, a combination with other autoimmune diseases (most often with nonspecific ulcerative colitis), disturbances in cellular and humoral immunity, and the detection of autoantibodies (antinuclear, to smooth muscles, to neutrophil cytoplasm).

Autoimmune cholangitis is a chronic cholestatic liver disease caused by immunosuppression. The histological picture of liver tissue in this disease is almost identical to primary biliary cirrhosis of the liver, and the spectrum of antibodies includes increased titers of antinuclear and antimitochondrial antibodies. Autoimmune cholangitis is apparently not a variant of primary sclerosing cholangitis.

The presence of antinuclear antibodies in patients with chronic autoimmune hepatitis is one of the main indicators that allows distinguishing this disease from protracted 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, antinuclear antibodies can be found in low titers in practically healthy people, and their titer increases with age. They can appear after taking certain medications, such as procainamide, methyldopa, certain anti-tuberculosis and psychotropic drugs. Very often, the titer of antinuclear antibodies increases in healthy women during pregnancy.

To confirm the autoimmune nature of liver damage and to conduct differential diagnostics of various forms of autoimmune hepatitis and primary biliary cirrhosis, diagnostic tests have been developed that allow the determination of antimitochondrial antibodies (AMA), antibodies to smooth muscles, antibodies to liver-specific lipoprotein and liver membrane antigen, antibodies to microsomal liver and kidney antigen, antibodies to neutrophils, etc.

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