Primary sclerosing cholangitis

Last updated: August 2, 2022

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Primary sclerosing cholangitis (PSC) is a progressive chronic inflammation of both the intrahepatic and extrahepatic bile ducts. The exact etiology is unknown but there is a strong association with autoimmune diseases, particularly ulcerative colitis (UC). In the early stages, PSC is often asymptomatic. As the disease progresses, patients may present with right upper quadrant abdominal pain, pruritus, fatigue, and weight loss. Laboratory tests show findings of cholestasis, including elevated alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT). While not recommended for diagnosis, pANCA is positive in up to 80% of cases. Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) is used for diagnostic confirmation. Management is primarily symptomatic, with liver transplantation reserved for end-stage liver disease.

  • Sex: : > (2:1)
  • Age: : The median age at diagnosis is ∼ 40.

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

The majority of patients with PSC also have ulcerative colitis.References:[1][2]

References:[2]

Approach [3][4]

The diagnosis of PSC is based on persistently elevated cholestatic enzymes, characteristic bile duct strictures seen on MRCP or ERCP, and the exclusion of secondary sclerosing cholangitis. [4]

Laboratory studies [3][4][5]

Routine studies

Suspect PSC in patients with a history of inflammatory bowel disease and elevated cholestatic enzymes (ALP, GGT, and conjugated bilirubin).

Serological studies

Findings are typically nonspecific but may help support the diagnosis or differential diagnoses.

Serological studies in patients with suspected PSC [3][4]
Autoantibodies
Immunoglobulins

All patients should be tested for elevated IgG4 at least once, as findings may influence management. [3][4]

Imaging [3][4][7]

Initial imaging

Obtain abdominal imaging for all patients to evaluate for biliary obstruction.

Advanced imaging

Obtain for all patients for diagnostic confirmation.

Liver biopsy [3]

Differential diagnoses of cholestatic biliary disease

Primary sclerosing cholangitis Primary biliary cholangitis

Secondary sclerosing cholangitis [8][9]

Epidemiology
  • More common among middle-aged men

  • More common among middle-aged women

  • Depends on the underlying condition
Pathophysiology
  • Progressive destruction of only intrahepatic small and medium-sized bile ducts

Clinical presentation
  • Similar to PSC
  • Additional symptoms corresponding to the underlying condition
  • Poor prognosis
Laboratory tests
Associated conditions
  • Autoimmune conditions

The differential diagnoses listed here are not exhaustive.

General principles [3][4]

Pharmacological management [3][4][5]

Interventional treatment [3][4][5]

Perform as needed in patients with dominant strictures.

Patients with PSC are at increased risk for post-ERCP cholangitis. [3]

Liver transplantation [3][4]

Screening and monitoring [3][4][7]

Patients with PSC are at increased risk of IBD, progression of liver disease to cirrhosis, osteoporosis, and malignancy.

Screening and monitoring of complications and comorbidities in PSC [3][4][7]
Modalities Timing
Inflammatory bowel disease
  • At time of PSC diagnosis, then:
    • Annually in patients with IBD
    • Consider every 3–5 years in patients without IBD. [3]
Colorectal carcinoma

Cholangiocarcinoma

  • Consider every 6–12 months.
Gallbladder carcinoma
  • Annually
Progression of liver disease
  • Obtain at diagnosis then regularly.
Osteoporosis
Complications of cirrhosis [11] Hepatocellular carcinoma
  • Every 6 months
Esophageal varices
  • At cirrhosis diagnosis
  • Then every 2–3 years

Patients with both PSC and UC have a 4–5 times higher risk of developing colorectal dysplasia or cancer than those with UC alone. [3][4]

  1. Abdalian R, Heathcote EJ. Sclerosing cholangitis: A focus on secondary causes. Hepatology. 2006; 44 (5): p.1063-1074. doi: 10.1002/hep.21405 . | Open in Read by QxMD
  2. Ruemmele P, Hofstaedter F, Gelbmann CM. Secondary sclerosing cholangitis. Nature Reviews Gastroenterology & Hepatology. 2009; 6 (5): p.287-295. doi: 10.1038/nrgastro.2009.46 . | Open in Read by QxMD
  3. Kowdley KV. Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/primary-sclerosing-cholangitis-in-adults-clinical-manifestations-and-diagnosis.Last updated: January 4, 2016. Accessed: December 26, 2016.
  4. Kowdley KV. Primary sclerosing cholangitis: Epidemiology and pathogenesis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/primary-sclerosing-cholangitis-epidemiology-and-pathogenesis.Last updated: January 13, 2015. Accessed: December 26, 2016.
  5. Lindor KD, Kowdley KV, Harrison EM. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015; 110 (5): p.646-659. doi: 10.1038/ajg.2015.112 . | Open in Read by QxMD
  6. Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010; 51 (2): p.660-678. doi: 10.1002/hep.23294 . | Open in Read by QxMD
  7. Prokopič M, Beuers U. Management of primary sclerosing cholangitis and its complications: an algorithmic approach. Hepatol Int. 2020; 15 (1): p.6-20. doi: 10.1007/s12072-020-10118-x . | Open in Read by QxMD
  8. Lazaridis KN, LaRusso NF. Primary Sclerosing Cholangitis. N Engl J Med. 2016; 375 (12): p.1161-1170. doi: 10.1056/nejmra1506330 . | Open in Read by QxMD
  9. Gochanour E, Jayasekera C, Kowdley K. Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, and Current Management. Clin Liver Dis (Hoboken). 2020 .
  10. Lemoinne S, Thabut D. Screening for esophageal varices.. Clin liver dis. 2012; 1 (5): p.143-146. doi: 10.1002/cld.101 . | Open in Read by QxMD
  11. Jorgensen RA, Lindor KD, Sartin JS, LaRusso NF, Wiesner RH. Serum Lipid and Fat-Soluble Vitamin Levels in Primary Sclerosing Cholangitis. J Clin Gastroenterol. 1995; 20 (3): p.215-219. doi: 10.1097/00004836-199504000-00011 . | Open in Read by QxMD
  12. Diagnosis and Management of Primary Sclerosing Cholangitis. https://www.aasld.org/sites/default/files/2019-06/PrimarySclerosingCholangitis2010.pdf. Updated: August 31, 2009. Accessed: January 13, 2021.
  13. Ponsioen C. Diagnosis, prognosis, and management of primary sclerosing cholangitis. Gastroenterology & Hepatology. 2013; 9 (7): p.453-65.

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