Review Article: Overlap Syndromes and Autoimmune Liver Disease

P. J. Trivedi; G. M. Hirschfield


Aliment Pharmacol Ther. 2012;36(6):517-533. 

In This Article

Abstract and Introduction


Background Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the family of autoimmune liver diseases, whereby the result of immune-mediated liver injury gives rise to varied clinical presentations. Some patients demonstrate a phenotype whereby there is evidence of either PBC or PSC together with overlapping features of AIH. Due to an absence of well-validated diagnostic criteria and a lack of large therapeutic trials, treatment of overlap conditions is empiric and extrapolated from data derived from the primary autoimmune liver diseases.
Aims To review overlaps in the context of autoimmune liver diseases.
Methods General and specific review of published articles using PubMed, Medline and Ovid search engines, alongside pre-existing clinical management protocols, guidelines, and the authors' own knowledge of the published literature.
Results The challenges in diagnosis, clinical presentation, determining natural history and outcome of overlaps are presented, as well as present-day management suggestions, some based on evidence, others on consensus and opinion.
Conclusions Overlapping autoimmune features, be they clinical, serological, histological or radiological are not infrequent, but appropriate diagnosis remains hindered by a lack of standardised diagnostic criteria. Optimum care for those with suspected overlap should thus focus on attention to detail over the fundamental aspects of timely secure diagnosis of the dominant disease entity. Clinicians should counsel patients carefully with regard to the risks and benefits of treatment, bearing in mind the paucity of randomised and controlled outcome data for medical interventions.


Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are characterised by a varying degree of immune-mediated liver injury, and although criteria exist which facilitate their timely diagnosis, shared serological, immunological and histological patterns exist across the spectrum of these three autoimmune liver diseases (Table 1). Conditions exhibiting features of two different autoimmune liver diseases are commonly designated 'overlap syndromes'; however, there is no current agreement on what constitutes an overlap, neither are there specific diagnostic criteria, suggesting that overlaps are not distinct entities as such. Thus, rather than representing a distinct disease process, these patterns of immune-mediated liver injury are likely a manifestation of the inherent distribution of clinical phenotypes across patient populations with immune-mediated hepatitis (interface activity) forming a fundamental component of most clinical overlap presentations. In this article, we provide an update on overlap syndromes, discussing the diagnostic and therapeutic challenges, which exist across the varied clinical presentations encountered in routine practice.


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