Overlap Syndromes of Primary Sclerosing Cholangitis

Abstract

Primary sclerosing cholangitis can have features of autoimmune hepatitis or primary biliary cholangitis. Overlapping features with primary biliary cholangitis occur in only 0.7 % of patients, but concurrent findings of autoimmune hepatitis occur in 4–17 %. Overlapping features can be present at onset or develop in sequence. Laboratory indices of marked liver inflammation, serological markers of immune reactivity, and histological findings of interface hepatitis with dense lymphoplasmacytic infiltration suggest an overlap syndrome with autoimmune hepatitis. Antimitochondrial antibodies and histological findings of destructive cholangitis suggest an overlap syndrome with primary biliary cholangitis. Overlap syndromes of primary sclerosing cholangitis involving the small bile ducts may have a better long-term prognosis than disease involving the large bile ducts. Treatment is directed at the predominant disease component and tailored to the individual response. Prednisolone and azathioprine have been the principal drugs used in treating the overlap syndrome with autoimmune hepatitis, and ursodeoxycholic acid has been the main drug used in treating the overlap syndrome with primary biliary cholangitis. The inflammatory indices commonly improve and may normalize in patients with features of autoimmune hepatitis, whereas the cholestatic indices usually remain abnormal. Histological progression can occur despite laboratory improvement, and survival has ranged from 56 to 100 %. Liver transplantation has been required in at least 19 %, and malignancies develop in 0–12 %. Patients with features of primary biliary cholangitis can improve liver tests to normal or near normal and remain stable for up to 17 years. Overlap syndromes must be considered in all patients with atypical manifestations and disease progression.