Diagnostic and therapeutic questions in overlap syndromes of autoimmune hepatitis

The term 'overlap syndromes of liver diseases' includes coexistence of autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC). Due to their unknown etiology, as well as their variable presentation with mixed clinical and biochemical features, these overlap syndromes are often a diagnostic and therapeutic challenge for hepatologists. The most frequent association reported occurs between AIH and PBC. More rare is the overlap between AIH and PSC, typical in young age and often concomitant with an inflammatory bowel disease as ulcerative colitis. The treatment of choice is based on ursodeoxycholic acid and immunosoppressive drugs, used at the same time or consecutively, according to the course of disease. Histological examination seems an important tool, but often does not help for a correct diagnosis due to lack of specificity. Two particular forms of variant syndrome are the so called outlier syndromes, without clear characteristics of overlap: the autoimmune cholangitis, probably a form of PBC anti-mitochondrial antibodies negative, and the hepatitis C virus related with stigmata of autoimmunity, such as nonspecific autoantibodies at low titer. The diagnostic score system elaborated in 1999 by the International AIH Group can help for diagnosis, even if its definite validity is lacking.