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Secondary sclerosing cholangitis

Nature Reviews Gastroenterology & Hepatology volume 6, pages 287–295 (2009)Cite this article

Abstract

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic biliary disease, characterized by inflammation, obliterative fibrosis of the bile ducts, stricture formation and progressive destruction of the biliary tree that leads to biliary cirrhosis. SSC is thought to develop as a consequence of known injuries or secondary to pathological processes of the biliary tree. The most frequently described causes of SSC are longstanding biliary obstruction, surgical trauma to the bile duct and ischemic injury to the biliary tree in liver allografts. SSC may also follow intra-arterial chemotherapy. Sclerosing cholangitis in critically ill patients is a largely unrecognized new form of SSC, and is associated with rapid progression to liver cirrhosis. The mechanisms leading to cholangiopathy in critically ill patients are widely unknown; however, the available clinical data indicate that ischemic injury to the intrahepatic biliary tree may be one of the earliest events in the development of this severe form of sclerosing cholangitis. Therapeutic options for most forms of SSC are limited, and patients with SSC who do not undergo transplantation have significantly reduced survival compared with patients with primary sclerosing cholangitis. Sclerosing cholangitis in critically ill patients, in particular, is associated with rapid disease progression and poor outcome.

Key Points

  • Secondary sclerosing cholangitis (SSC) may be caused by various insults to the biliary tree; main causes are chronic biliary obstruction, infectious or toxic cholangitis, immunological causes and ischemic cholangiopathies

  • SSC is a progressive disease characterized by fibrosis and destruction of the biliary tree, which leads to biliary cirrhosis; in most cases, the benefits of therapeutic interventions are limited

  • Sclerosing cholangitis in critically ill patients (SC–CIP) is a new entity of sclerosing cholangiopathy and is associated with a particularly rapid progression of the disease

  • The hallmark of SC–CIP is the early formation of biliary casts; the etiology of SC–CIP may involve early ischemic bile duct injury; however other factors are probably also involved

  • The clinical signs during the initial phase of SC–CIP are not specific; a diagnosis of SC-CIP is often overlooked and, therefore, the frequency of SC–CIP is probably underestimated

  • Aside from transplantation, there are no effective treatment options for SC–CIP; the median survival of patients with SC–CIP who do not undergo liver transplantation is only about 13 months

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Figure 1: Blood supply of the extrahepatic and intrahepatic biliary system.
Figure 2: Biliary cast formation in a patient 30 days after the first clinical signs of bile duct injury.
Figure 3
Figure 4
Figure 5: Liver biopsy sample.
Figure 6: Liver biopsy sample with a periportal bile duct infarct.
Figure 7: Liver biopsy sample showing perivenular hepatocellular bilirubinostasis, canalicular bilirubinostasis and hepatocellular damage.
Figure 8: Liver biopsy sample.
Figure 9: Section from an explanted liver.

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Acknowledgements

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. Department of Internal Medicine I, University of Regensburg, Germany

    Petra Ruemmele, Ferdinand Hofstaedter & Cornelia M. Gelbmann

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Ruemmele, P., Hofstaedter, F. & Gelbmann, C. Secondary sclerosing cholangitis. Nat Rev Gastroenterol Hepatol 6, 287–295 (2009). https://doi.org/10.1038/nrgastro.2009.46

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