Overlap Syndromes

Abstract

Background: Some patients present with features of both primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) on the one hand and autoimmune hepatitis (AIH) on the other hand, either simultaneously or consecutively. The term 'overlap syndrome (OS)' is used to describe these settings, but lack of universal agreement on what precisely constitutes an OS has generated considerable confusion. The low prevalence of OS (roughly 10% of PBC or PSC) has made it impracticable to perform randomized controlled trials. It remains unclear whether this syndrome forms a distinct entity or is a variant of PBC, PSC or AIH.

Key messages: Moderate to severe interface hepatitis is a fundamental component and histology is vital in evaluating patients with overlap presentation. Use of the International Autoimmune Hepatitis Group criteria for the diagnosis of OS is not recommended. For PBC-AIH OS, EASL has provided diagnostic criteria and, in most cases, it is possible to define one primary disorder ('dominant' disease), usually PBC. Patients with OS seem to have a more severe disease compared to conventional PBC. PSC-AIH OS is assumed to exist in a considerable part of mainly young patients with autoimmune liver disease and long-term progression towards cirrhosis seems to occur in the majority of cases. In children, the hepatitic feature can be very dominant, and up to 50% of pediatric AIH have cholangiographic abnormalities suggestive of PSC (autoimmune sclerosing cholangitis). Treatment of OS is empiric and includes ursodeoxycholic acid for the cholestatic component (depending on local policy for PSC) and immunosuppressive agents for the hepatitic component, either simultaneously or sequentially. The dominant clinical feature should be treated first and therapy adjusted according to the response.

Conclusions: OS is not uncommon but should not be over-diagnosed in order not to expose unnecessarily PBC or PSC patients to the risk of steroid side effects. Therapy has to be individualized and not be static.