TABLE 2.

Pathogenic hypotheses for the overlap syndromes of autoimmune hepatitis (AIH)

Hypothesis	Theoretical bases	Clinical evidence
Classical AIH with atypical features	AIH features not disease specific (52) AIH features occur in multiple acute and chronic liver diseases (16) Diagnostic scoring systems are based on classical AIH and not valid in atypical phenotypes (7,32)	AIH overlapping with PBC or PSC can respond to conventional corticosteroid therapy (2,18,20,41) AIH, PBC and PSC have many shared laboratory, serological, genetic and histological findings that are not disease specific (59)
Transitional stage in evolution to classical PBC or PSC	Autoimmune liver diseases evolve through early formative stages that have mixed features (34,59)	Histological findings are indistinguishable among PBC, stage 2 and AIH (34) AIH has evolved into PBC and PSC, and PBC has evolved into AIH (53–55)
Concurrent separate diseases	Common genetic factors in AIH, PBC and PSC may predispose to concurrent separate diseases (59)	Highly disease-specific findings (cholangiographic changes, destructive cholangitis) occur in AIH (49) PBC and PSC have coexisted (60–62)
Unrecognized new disease	Promiscuous immune response can target multiple targets in liver and biliary tree and create various phenotypes (63,75)	None

Numbers in parentheses refer to references. PBC Primary biliary cirrhosis; PSC Primary sclerosing cholangitis