12
Primary sclerosing cholangitis

https://doi.org/10.1016/j.bpg.2010.07.005Get rights and content

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.

Section snippets

Variations in clinical presentation

Onset of PSC is typically insidious. In many cases the diagnostic scenario is that of a patient with IBD presenting with elevated hepatic biochemistries,[18] followed by cholangiography and appropriate supplementary biochemical tests and in some cases liver histology (Table 1). [19], [20] In recent case series, approximately half of the PSC patients are asymptomatic at diagnosis.[7], [21] Other patients may exhibit non-specific symptoms (e.g. fatigue, abdominal pain), clinical features related

Disease course in PSC

Regarding symptoms and hepatic biochemistries, disease course in PSC is initially fluctuating and often quiescent, with more steady progression only observed alongside advanced stages of cirrhosis (Fig. 1). At the histological level, four stages describing the progressive nature of PSC have been defined.[41] In the early stage, biopsy specimens may be normal or show only mild portal oedema, inflammation and proliferation of the small bile ducts. Typically, these lesions appear side by side with

Liver transplantation in PSC

In the Nordic countries, PSC is the most important indication for liver transplantation. In the US, PSC is among the five leading indications, and even in low-prevalence countries like Italy and Spain, PSC is among the ten most common indications. For patients with end-stage cirrhosis, timing of liver transplantation in PSC does not differ from that of other indications for liver transplantation (e.g. consideration of MELD score and local waiting times). However, in addition to liver cirrhosis

Post-transplant course of PSC

An increased frequency of acute cellular rejection in PSC has been reported in several studies.[85], [86], [87] Based on these observations, some authorities recommend an intensified immunosuppressive regimen including life-long corticosteroids following liver transplantation for PSC.[84] The basis of the increased risk is not known. Recent data suggest a possible role of KIR signalling in T-lymphocytes and natural killer cells.[88], [89] Both studies were related to HLA-C, in line with the

Summary

The main challenges in PSC are related to the scarce knowledge on aetiology, the variable disease course and the high risk of cholangiocarcinoma. Consequently, establishing therapeutic strategies on the basis of pathogenetic knowledge has so far not been possible, and validated strategies for follow-up of the individual PSC patient regarding timing of liver transplantation and early detection of malignancies have so far not been established. However, apart from the importance of detecting

Conflict of interest

None.

References (100)

  • R.H. Wiesner et al.

    Clinicopathologic features of the syndrome of primary sclerosing cholangitis

    Gastroenterology

    (1980)
  • J. Ludwig et al.

    Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis

    Hepatology

    (1986)
  • D.J. Brandt et al.

    Gallbladder disease in patients with primary sclerosing cholangitis

    AJR Am J Roentgenol

    (1988)
  • K.M. Boberg et al.

    Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population

    Scand J Gastroenterol

    (1998)
  • A. Escorsell et al.

    Epidemiology of primary sclerosing cholangitis in Spain. Spanish Association for the Study of the Liver

    J Hepatol

    (1994)
  • T.L. Ang et al.

    Clinical profile of primary sclerosing cholangitis in Singapore

    J Gastroenterol Hepatol

    (2002)
  • U. Broome et al.

    Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis

    Gut

    (1996)
  • E. Aadland et al.

    Primary sclerosing cholangitis: a long-term follow-up study

    Scand J Gastroenterol

    (1987)
  • R.H. Wiesner

    Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease

    Best Pract Res Clin Gastroenterol

    (2001)
  • K.M. Boberg et al.

    Hepatobiliary disease in ulcerative colitis. An analysis of 18 patients with hepatobiliary lesions classified as small-duct primary sclerosing cholangitis

    Scand J Gastroenterol

    (1994)
  • F. Alvarez et al.

    International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis

    J Hepatol

    (1999)
  • O. Fausa et al.

    Relationship of inflammatory bowel disease and primary sclerosing cholangitis

    Semin Liver Dis

    (1991)
  • E.V. Loftus et al.

    PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis

    Gut

    (2005)
  • M. Joo et al.

    Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study

    Am J Surg Pathol

    (2009)
  • R.M. Soetikno et al.

    Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis

    Gastrointest Endosc

    (2002)
  • J.E. Hay et al.

    Primary sclerosing cholangitis and celiac disease. A novel association

    Ann Intern Med

    (1988)
  • S. Saarinen et al.

    Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis

    Am J Gastroenterol

    (2000)
  • F.D. Mendes et al.

    Abnormal hepatic biochemistries in patients with inflammatory bowel disease

    Am J Gastroenterol

    (2007)
  • R. Chapman et al.

    Diagnosis and management of primary sclerosing cholangitis

    Hepatology

    (2010)

  • EASL Clinical Practice Guidelines: management of cholestatic liver diseases

    J Hepatol

    (2009)
  • J.J. Tischendorf et al.

    Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: A single center study

    Am J Gastroenterol

    (2007)
  • E. Schrumpf et al.

    Sclerosing cholangitis in ulcerative colitis

    Scand J Gastroenterol

    (1980)
  • R.W. Chapman et al.

    Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology

    Gut

    (1980)
  • T.R. Riley et al.

    A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease

    Am J Gastroenterol

    (1997)
  • R. Abdalian et al.

    Sclerosing cholangitis: a focus on secondary causes

    Hepatology

    (2006)
  • E.V. Sandborn et al.

    Primary sclerosing cholangitis is associated with nonsmoking: a case-control study

    Gastroenterology

    (1996)
  • T.H. Karlsen et al.

    The utility of genome-wide association studies in hepatology

    Hepatology

    (2010)
  • A. Bergquist et al.

    Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis

    Clin Gastroenterol Hepatol

    (2008)
  • T.H. Karlsen et al.

    Genome-wide association analysis in primary sclerosing cholangitis

    Gastroenterology

    (2010)
  • T.H. Karlsen et al.

    Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis

    Genes Immun

    (2007)
  • T.H. Karlsen et al.

    Genetic Polymorphisms Associated With Inflammatory Bowel Disease Do Not Confer Risk for Primary Sclerosing Cholangitis

    Am J Gastroenterol

    (2006)
  • T.H. Karlsen et al.

    Particular genetic variants of ligands for natural killer cell receptors may contribute to the HLA associated risk of primary sclerosing cholangitis

    J Hepatol

    (2007)
  • J.R. Hov et al.

    Genetic associations in Italian primary sclerosing cholangitis: heterogeneity across Europe defines a critical role for HLA-C

    J Hepatol

    (2010)
  • P.M.H.C. Parham

    class I molecules and KIRs in human history, health and survival

    Nat Rev Immunol

    (2005)
  • T.H. Karlsen et al.

    Update on primary sclerosing cholangitis

    Dig Liver Dis

    (2010)
  • V. Keitel et al.

    The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders

    Hepatology

    (2009)
  • V. Keitel et al.

    Expression and function of the bile acid receptor TGR5 in Kupffer cells

    Biochem Biophys Res Commun

    (2008)
  • C. Colombo

    Liver disease in cystic fibrosis

    Curr Opin Pulm Med

    (2007)
  • P.G. Blanco et al.

    Induction of colitis in cftr-/- mice results in bile duct injury

    Am J Physiol Gastrointest Liver Physiol

    (2004)
  • A. Franke et al.

    Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility

    Nat Genet

    (2008)
  • J. Ludwig

    Surgical pathology of the syndrome of primary sclerosing cholangitis

    Am J Surg Pathol

    (1989)
  • K.W. Burak et al.

    Is there a role for liver biopsy in primary sclerosing cholangitis?

    Am J Gastroenterol

    (2003)
  • W.R. Kim et al.

    A revised natural history model for primary sclerosing cholangitis

    Mayo Clin Proc

    (2000)
  • K.M. Boberg et al.

    Time-dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis

    Hepatology

    (2002)
  • E.R. Dickson et al.

    Primary sclerosing cholangitis: refinement and validation of survival models

    Gastroenterology

    (1992)
  • E. Bjornsson et al.

    Dominant strictures in patients with primary sclerosing cholangitis

    Am J Gastroenterol

    (2004)
  • R.A. Kozarek

    Endoscopic therapy in primary sclerosing cholangitis. Dominant strictures may not matter: does that mean that endotherapy does not work?

    Am J Gastroenterol

    (2004)
  • E. Bjornsson et al.

    Dominant strictures in patients with primary sclerosing cholangitis-revisited

    Am J Gastroenterol

    (2004)
  • R.G. Olsson et al.

    Prognostic value of cholangiography in primary sclerosing cholangitis

    Eur J Gastroenterol Hepatol

    (1995)
  • D.A. Craig et al.

    Primary sclerosing cholangitis: value of cholangiography in determining the prognosis

    AJR Am J Roentgenol

    (1991)

    • Cited by (0)

    View full text
    Copyright © 2010 Elsevier Ltd. All rights reserved.