Diagnosis and Management of the Overlap Syndromes of Autoimmune Hepatitis

Abstract

BACKGROUND: Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These cholestatic phenotypes have been designated ‘overlap syndromes’.OBJECTIVES: To recognize the overlap syndromes in adults and manage them appropriately.METHODS: The MEDLINE database was reviewed for published experiences from 1984 to 2013.RESULTS: Patients with autoimmune hepatitis may exhibit features of primary biliary cirrhosis (7% to 13%), primary sclerosing cholangitis (6% to 11%) or a cholestatic syndrome without other diagnostic features (5% to 11%). These mixed phenotypes may represent classical autoimmune hepatitis with atypical features, transition states in the evolution of classical cholestatic syndromes, concurrent separate diseases or pathogenically distinct disorders. The ‘Paris criteria’ have been endorsed for the diagnosis of the overlap syndrome with primary biliary cirrhosis, and treatment with conventional immunosuppressive therapy alone or in combination with low-dose ursodeoxycholic acid can be guided by the serum alkaline phosphatase level. The overlap syndrome with primary sclerosing cholangitis or with cholestasis without diagnostic features is commonly treated with immunosuppressive therapy and ursodeoxycholic acid. Responses are variable and commonly incomplete (20% to 100% improvement) depending on the degree of cholestasis.DISCUSSION: The overlap syndromes are clinical descriptions rather than pathological entities, and the dominant component of the disease determines its designation and therapy. Cholestatic findings in autoimmune hepatitis influence the response to immunosuppressive therapy.CONCLUSION: The overlap syndromes must be considered in patients with autoimmune hepatitis and cholestatic findings, concurrent inflammatory bowel disease or steroid-refractory disease.