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  • Review Article
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IgG4-related hepatobiliary disease: an overview

Nature Reviews Gastroenterology & Hepatology volume 13, pages 601–612 (2016)Cite this article

Subjects

Key Points

  • IgG4-related hepatobiliary diseases (IgG4-HBD) are part of a systemic fibroinflammatory condition, termed IgG4-related disease. IgG4-HBD includes IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy

  • IgG4-HBD can present with abnormal liver biochemistry, biliary strictures and/or masses, impeding the differentiation from other benign and malignant hepatobiliary disorders

  • Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. A gold standard diagnostic test is lacking, although novel markers might help to differentiate IgG4-HBD from other conditions

  • Treatment regimens have been reached by international consensus but are not supported by randomized controlled trials. First-line therapy is corticosteroids, often in combination with biliary stenting for patients with IgG4-SC

  • The long-term outcome in IgG4-HBD is not well established. Disease-related inflammatory and fibrotic complications and an increased risk of all-cause malignancy have been reported in prospective studies

  • Insights into the genetic and immunological aspects of disease pathogenesis have increased over the past decade. Defining the initiating and driving factors for fibrotic disease remains an important challenge

Abstract

IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers. Novel assays — such as the serum IgG4:IgG1 ratio and IgG4:IgG RNA ratio (which distinguish IgG4-SC from PSC with high serum IgG4 levels), and plasmablast expansion to recognize IgG4-SC with normal serum IgG4 levels — require further validation. Steroids and other immunosuppressive therapies can lead to clinical and radiological improvement when given in the inflammatory phase of the disease, but evidence for the efficacy of treatment regimens is limited. Progressive fibrosclerotic disease, liver cirrhosis and an increased risk of malignancy are now recognized outcomes. Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system.

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Figure 1: Histological sections of IgG4-related sclerosing cholangitis.
Figure 2: The pathogenesis of IgG4-related disease.

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Authors and Affiliations

  1. Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU, Oxford, UK

    Emma L. Culver & Roger W. Chapman

  2. Nuffield Department of Medicine, Oxford University, Old Road Campus, Headington, OX3 7BN, Oxford, UK

    Emma L. Culver & Roger W. Chapman

  3. Liver Transplant Unit, Royal Free Hospital, Pond Street, London, NW3 2QG, UK

    Emma L. Culver

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  1. Emma L. Culver
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E.L.C. wrote the article, researched data and provided a substantial contribution to discussions of the content. E.L.C. and R.W.C. contributed equally to the reviewing and/or editing of the manuscript before submission

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Correspondence to Roger W. Chapman.

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Supplementary information

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IgG4 antibody structure and function (PDF 111 kb)

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Autoantibodies and/or autoantigens in AIP (and IgG4-SC) (PDF 121 kb)

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IgG4 autoantibodies and/or antigens in non-IgG4-RD (PDF 124 kb)

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Culver, E., Chapman, R. IgG4-related hepatobiliary disease: an overview. Nat Rev Gastroenterol Hepatol 13, 601–612 (2016). https://doi.org/10.1038/nrgastro.2016.132

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