Liver Immunology, Principles and Practice, Third Edition Chapter 24: Primary Biliary Cholangitis: Autoimmune Hepatitis Overlap Syndrome

*Some patients present with features of both primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) 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) has made it impracticable to perform randomized controlled trials. • It remains unclear whether this syndrome forms a distinct entity or, more likely, a variant of PBC, or AIH. • 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. • Treatment of OS is empiric and includes ursodeoxycholic acid (UDCA) for the cholestatic component and immunosuppressive agents for the hepatitic component, either simultaneously or sequentially. Immunosuppressive treatment in addition to UDCA is recommended in patients with severe interface hepatitis and deserves consideration in those with moderate interface hepatitis. • The dominant clinical feature should be treated first and therapy adjusted according to the response. • OS is not uncommon but should not be over-diagnosed in order not to expose unnecessarily PBC patients to the risk of steroid side effects. Therapy has to be individualized and not be static.