We searched PubMed with the term “primary sclerosing cholangitis” for articles in English published between Dec 1, 2007, and Dec 1, 2012, to identify medical literature in addition to that familiar to the authors or cited by guidelines. Older references were included if informative. References were selected on the basis of their ability to provide composite insight into primary sclerosing cholangitis and guide the reader to relevant primary and secondary sources for further reading.
SeminarPrimary sclerosing cholangitis
Introduction
Primary sclerosing cholangitis is a challenging illness that is characterised by chronic bile duct destruction and progression to end-stage liver disease. No effective medical treatments are available.1, 2, 3 Systematic review of published reports shows that incidence varies geographically and is as high as 1·3 per 100 000 people per year in northern Europe; prevalence also varies but reaches 16·2 per 100 000 people in some studies.4, 5, 6 Although primary sclerosing cholangitis affects both sexes and all age groups, more than 60% of patients are men and the median age at onset is 30–40 years.4, 5, 6
Patients are usually non-smokers, and 60–80% of cases in northern European populations are clearly associated with inflammatory bowel disease (compared with 30–50% of cases in southern European and Asian populations). For example, in a large study,7 roughly two-thirds of 579 patients with primary sclerosing cholangitis had coexistent inflammatory bowel disease (around 75% of whom had ulcerative colitis). 207 (83%) of the patients with ulcerative colitis had a pancolitis, 32 (13%) a left-sided colitis, and 9 (4%) proctitis only. 70 (95%) of those with Crohn's disease had an ileocolitis and four (5%) ileitis only. Primary sclerosing cholangitis without colitis probably shows the effects of a mosaic of interacting genetic and environmental risks of different strengths, although colitis or immune activation in the gut might simply be too mild to be diagnosed by available techniques.
More than 50% of patients need liver transplantation within 10–15 years of symptom development, as a result of reduced quality and quantity of life related to biliary obstruction, cholangitis, secondary biliary cirrhosis, and hepatobiliary malignant disease.8, 9, 10
Section snippets
Clinical features
Sclerosing cholangitis covers a range of cholangiopathies that can be detected radiologically or histopathologically (or both) and are usually accompanied by cholestatic biochemical profiles (Figure 1, Figure 2). Disease with no known precipitant is deemed primary, whereas that arising from identifiable insults to the biliary tree is termed secondary disease (the appendix contains a differential diagnosis). Many secondary causes, including autoimmunity (ie, IgG4-associated autoimmune
Vascular changes
Improved imaging with MRI and an increase in routine testing of liver biochemistry mean that primary sclerosing cholangitis is now diagnosed earlier than previously (figure 4), and before cholangiography shows a severe generalised beading of the biliary tree and stenosis (which is how most cases were diagnosed previously).4 Symptoms can be liver-specific (itch, pain) or non-specific (fatigue) and can impair quality of life.46
Patients who also have inflammatory bowel disease are more likely to
Management
Management of patients with primary sclerosing cholangitis is multimodality based and requires a team of specialists with varying skills. The absence of definitive evidence often means practice is based on expert opinion and local expertise. Primary sclerosing cholangitis can be unpredictable, and therefore periodic follow-up in specialist centres is often helpful for patients, as is involvement with support groups. Little absolute evidence for care of patients is available (Table 1, Table 2;
Conclusion
Synergistic insights into primary sclerosing cholangitis are arising from in-vitro experiments, animal models, genetic studies, and evolving notions and investigations of the interactions between the gut microbiota and immunological factors. Collectively, these approaches should define pathways to chronic biliary injury, and show rational targets for intervention. International collaborations and strong support from patients for research efforts worldwide shows how a previously bleak diagnosis
Search strategy and selection criteria
References (141)
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Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review
J Hepatol
(2012) - et al.
High lifetime risk of cancer in primary sclerosing cholangitis
J Hepatol
(2009) - et al.
Genome-wide association analysis in primary sclerosing cholangitis
Gastroenterology
(2010) - et al.
Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci
J Hepatol
(2012) - et al.
Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice
Gastroenterology
(2004) - et al.
24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice
Gastroenterology
(2006) - et al.
Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease
Am J Pathol
(2002) - et al.
Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease
Lancet
(2002) - et al.
MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease)
Hepatology
(2001) - et al.
FXR and PXR: potential therapeutic targets in cholestasis
J Steroid Biochem Mol Biol
(2012)