Overlap syndromes among autoimmune liver diseases

Abstract

The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardised definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.

Figure 1

Overlap syndrome autoimmune hepatitis-primary biliary cirrhosis. A 57-year-old woman presented with elevated γ-GT (2 × ULN) and transaminases (AST 2.5 × ULN, ALT 5.5 × ULN), and normal bilirubin. Serum AMA (1:3840), AMA-M2,ASMA and SLA were positive. Her immunoglobulins showed elevated IgG (23.2 g/L) and IgM (3.3 g/L). A liver biopsy disclosed an interface hepatitis and mild portal fibrosis without evidence of cirrhosis. A: HE, × 20; B: HE, × 40 (Courtesy of Prof. Dr. Müller-Höcker, Munich).