Russian Federation
The autoimmune liver diseases are among the most severe autoimmune diseases and often become the cause of hepatic cirrhosis. Recently special attention has been paid to autoimmune crossing of the two most frequent autoimmune diseases – autoimmune hepatitis and primary biliary cholangitis. The patient of this group are at high risk of developing hepatic cirrhosis with complications and need combined therapy of autoimmune hepatitis and primary biliary cholangitis, which indicates the need for improvingmethods of early diagnostics and therapy of their crossing.
autoimmune liver diseases, autoimmune hepatitis, primary biliary cholangitis, autoimmune crossing syndrome, variant syndrome, hepatic cirrhosis
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