Diagnosis of autoimmune liver disease

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 mainly 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 the results of liver tests, characteristic of hepatitis (bilirubin increased 2-10 times, the activity of transaminases is 5-10 times or more, the de Ritis coefficient is less than 1, the activity of alkaline phosphatase is increased slightly or moderately, an increase in the concentration of AFP, which correlates with the biochemical activity of the disease ).
• Hypergammaglobulinemia exceeding the norm is 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.

Autoimmune diseases of the liver include primary biliary cirrhosis, which manifests itself in the form of a low-symptomatic chronic destructive nephrotic cholangitis, which ends with 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 the liver tissue in this disease is almost identical to the primary biliary cirrhosis, and the antibody spectrum includes elevated titers of antinuclear and antimitochondrial antibodies. Autoimmune cholangitis, apparently, is 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 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 certain medications, such as procainamide, methyldopa, certain anti-tuberculosis and psychotropic drugs. Very often the titer of anti-nuclear antibodies is increased in healthy women during pregnancy.

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

[1], [2], [3], [4], [5]