Journal of Gastroenterology and Hepatology (2004) 19, S284–S286 DOI: 10.1111/j.1400-1746.2004.03688.x Blackwell Science, LtdOxford, UKJGHJournal of Gastroenterology and Hepatology0815-93192004 Blackwell Publishing Asia Pty LtdDecember 200419S7S284S286Original Article Overlap syndromes from pediatrics to adulthoodD Bogdanos et al. Correspondence: Giorgina Mieli-Vergani, Professor of Paediatric Hepatology, Paediatric Liver Service, Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Email: giorgina.vergani@kcl.ac.uk Overlap syndromes from pediatrics to adulthood DIMITRIOS BOGDANOS, DIEGO VERGANI AND GIORGINA MIELI-VERGANI Institute of Liver Studies, King’s College Hospital, Denmark Hill, London, UK Abstract Overlap syndromes are autoimmune conditions with mixed immunological, clinical and his- tological features. The most frequent overlaps are between primary biliary cirrhosis (PBC) and auto- immune hepatitis (AIH), and between AIH and sclerosing cholangitis (SC). True AIH/PBC overlap syndrome is rare and characterized by elevation of transaminases and immunoglobulin G (IgG), positive anti-smooth muscle antibodies and a liver biopsy showing interface hepatitis as well as changes typical of PBC. These patients respond to immunosuppressive treatment that must be given promptly, to avoid progression to liver failure. The so-called ‘autoimmune cholangitis’ defines a small group of patients with cholestatic and histological features of PBC but negative for anti-mitochondrial antibody (AMA) and positive for PBC-specific anti-nuclear antibody (ANA). The positivity for ANA in these patients is a con- sequence of the AMA negativity, since AMA masks ANA on immunofluorescence. These patients’ clin- ical course and response to treatment resemble that of classical PBC. AIH/ASC overlap syndrome is characterised by elevated levels of IgG and circulating autoantibodies, including ANA, SMA and atypical perinuclear anti-neutrophil cytoplasmic antibody, in association with cholangiographic changes typical of SC. This condition affects in particular children and young adults and may represent the early stage of adult primary SC. The parenchymal liver inflammation responds satisfactorily to immunosuppression, while the bile duct damage may progress despite treatment. © 2004 Blackwell Publishing Asia Pty Ltd Key words: autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, overlap. INTRODUCTION Syndromes with clinical, biochemical and histological features overlapping between different types of autoim- mune liver disorders have been described both in adults and children, and include primary biliary cirrhosis (PBC)/autoimmune hepatitis (AIH) and AIH/scleros- ing cholangitis (SC) overlap syndromes. PBC/AIH OVERLAP SYNDROME AIH and PBC are generally differentiated easily on the basis of serological, biochemical, clinical, and histolog- ical findings. The biochemical profile of PBC is most consistent with cholestasis, and the serologic hallmark is the presence of antimitochondrial antibodies (AMA). 1– 3 Liver histology in PBC typically shows destruction and loss of small bile ducts with portal inflammatory cell infiltration, and granulomas are frequently noted (non- suppurative destruction cholangitis or granulomatous cholangitis). 2,4,5 Parenchymal inflammation is usually mild, but may be considerable. 4,5 In type 1 AIH, the biochemical pattern is that of ‘hepatitis’; serological testing reveals a prominent elevation of immunoglobu- lin G (IgG) and immunological screening shows posi- tivity for antismooth muscle antibodies (ASMA) and/or antinuclear antibodies (ANA). 6 The histological hall- mark of AIH is interface hepatitis, characterized by mononuclear cells, lymphocytes, plasma cells and mac- rophages, infiltrating the portal tract, invading the adja- cent parenchyma and surrounding dying hepatocytes. Bile duct damage may be present but is infrequent. 7 Rarely, clinical, biochemical, and/or histological fea- tures reminiscent of both PBC and AIH overlap, and classification of a given patient’s chronic liver disease is enigmatic. The specific therapies for PBC and AIH are different. While corticosteroids or other immunosup- pressive drugs are of great benefit for patients with AIH 6 they may enhance osteoporosis in patients with PBC. 8 Whether the PBC–AIH overlap syndrome must be treated as PBC with ursodeoxycholic acid (UDCA) or as AIH with corticosteroids or a combination is a sub-