Primary Sclerosing Cholangitis Workup
- Author: Vikas Khurana, MD, FACP, FACG; Chief Editor: Julian Katz, MD more...
Liver function tests and histology are used in the evaluation of patients with suspected primary sclerosing cholangitis (PSC).
Liver function tests are the most valuable in the laboratory workup, including serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia. The most important imaging study is endoscopic retrograde cholangiopancreatography (ERCP). Transhepatic cholangiography and magnetic resonance cholangiopancreatography may also be utilized. The most common characteristic histologic feature is onion skin fibrosis (concentric periductal fibrosis) (see the image below). Liver biopsy is rarely diagnostic of PSC, although it does help determine both the stage and the prognosis of the disease.
Liver function tests
The most valuable lab studies in PSC are liver function tests. Serum alkaline phosphatase dominates the profile, which is cholestatic in nature. levels are usually 3-5 times reference-range values. Alkaline phosphatase can be divided into its various fractions to ascertain its origin from liver disease, as opposed to bone disease. Serum gamma-glutamyl transpeptidase levels mirror this rise and can help differentiate cholestasis from bone disease. Some patients with hypothyroidism, hypophosphatemia, or zinc or magnesium deficiency may have normal alkaline phosphatase levels.
Serum aminotransferase levels are increased but not markedly so. Serum bilirubin levels, with the conjugated component, are usually increased, but fluctuations in the level can occur. Serum albumin levels decrease later in the course of the disease, and the presence of hypoalbuminemia earlier in the disease may indicate active inflammatory bowel disease (IBD).
Hypergammaglobulinemia is present in 30% of patients, and 50% have increased immunoglobulin (IgM) levels. Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are present in 84% of patients; anticardiolipin (aCL) antibodies, in 66%; and antinuclear antibodies (ANA), in 53%.
Endoscopic retrograde cholangiopancreatography (ERCP) is considered the criterion standard for confirming a diagnosis of primary sclerosing cholangitis. ERCP findings include multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts. Transhepatic cholangiography is performed when ERCP is unsuccessful. Because it is noninvasive, magnetic resonance cholangiopancreatography (MRCP) is rapidly developing as the preferred study to evaluate the bile ducts. As image quality continues to improve, MRCP may become the preferred study.
See the related images below.
Magnetic resonance elastography (MRE) measurement of liver stiff appears to show promise as a potential biomarker in chronic liver disease. In a retrospective review of 266 patients with primary sclerosing cholangitis, MRE not only showed a 100% sensitivity and 94% specificity for detecting cirrhosis, but it was also predictive of the development of decompensated liver disease. The investigators noted that advanced liver stiffness was unlikely in the presence of a serum alkaline phosphatase level less than 1.5 times the upper limit of normal.
A variety of histopathologic liver changes are noted in patients with PSC. The most common characteristic feature is onion skin fibrosis (see the image below), which describes the appearance of periductal concentric fibrosis around the interlobular and septal bile ducts. This is present in only half of all biopsy specimens from patients with otherwise typical primary sclerosing cholangitis, whereas concentric fibrosis with obliteration of the small ducts (obliterative fibrous cholangitis)—a virtually diagnostic histopathologic lesion—is found in less than 10% of biopsy specimens. Periductal fibrosis may be accompanied by infiltrates of inflammatory cells. Piecemeal necrosis, as occurs in patients with chronic hepatitis, may be observed as well.
Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015 May. 110 (5):646-59; quiz 660. [Medline].
Rossi RE, Conte D, Massironi S. Primary sclerosing cholangitis associated with inflammatory bowel disease: an update. Eur J Gastroenterol Hepatol. 2016 Feb. 28 (2):123-31. [Medline].
Sarkar S, Bowlus CL. Primary sclerosing cholangitis: multiple phenotypes, multiple approaches. Clin Liver Dis. 2016 Feb. 20 (1):67-77. [Medline].
Chaparro M, Trapero-Marugán M, Guijarro M, López C, Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and primary sclerosing cholangitis: A case report and a short review of the literature. J Crohns Colitis. 2012 Apr 30. [Medline].
Gotthardt D, Chahoud F, Sauer P. Primary sclerosing cholangitis: diagnostic and therapeutic problems. Dig Dis. 2011. 29 Suppl 1:41-5. [Medline].
Shneider BL. Diagnostic and therapeutic challenges in pediatric primary sclerosing cholangitis. Liver Transpl. 2011 Dec 5. [Medline].
Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, et al. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat Genet. 2013 Jun. 45(6):670-5. [Medline]. [Full Text].
Trottier J, Bialek A, Caron P, Straka RJ, Heathcote J, Milkiewicz P, et al. Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study. Dig Liver Dis. 2011 Dec 8. [Medline].
Næss S, Shiryaev A, Hov JR, Franke A, Karlsen TH. Genetics in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol. 2012 May 1. [Medline].
Okada H, Mizuno M, Yamamoto K, Tsuji T. Primary sclerosing cholangitis in Japanese patients: association with inflammatory bowel disease. Acta Med Okayama. 1996 Oct. 50(5):227-35. [Medline].
Kim WR, Therneau TM, Wiesner RH, et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc. 2000 Jul. 75(7):688-94. [Medline].
Mayo Foundation for Medical Education and Research. The Revised Natural History Model for Primary Sclerosing Cholangitis. Available at http://www.mayoclinic.org/gi-rst/mayomodel3.html. Accessed: October 18, 2014.
Shetty K, Rybicki L, Carey WD. The Child-Pugh classification as a prognostic indicator for survival in primary sclerosing cholangitis. Hepatology. 1997 May. 25(5):1049-53. [Medline].
Rupp C, Rössler A, Halibasic E, et al. Reduction in alkaline phosphatase is associated with longer survival in primary sclerosing cholangitis, independent of dominant stenosis. Aliment Pharmacol Ther. 2014 Oct 14. [Medline].
Ananthakrishnan AN, Beaulieu DB, Ulitsky A, Zadvornova Y, Skaros S, Johnson K, et al. Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?. Inflamm Bowel Dis. 2009 Jul 27. [Medline].
Abbas G, Lindor KD. Cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Cancer. 2009 Aug 25. epub ahead of print. [Medline].
Jesudian AB, Jacobson IM. Screening and diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis. Rev Gastroenterol Disord. 2009 Spring. 9(2):E41-7. [Medline].
Ludwig J, Barham SS, LaRusso NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981 Nov-Dec. 1(6):632-40. [Medline].
Kato T, Komori A, Bae SK, Migita K, Ito M, Motoyoshi Y, et al. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis. World J Gastroenterol. 2012 Jan 14. 18(2):192-6. [Medline]. [Full Text].
Eaton JE, Dzyubak B, Venkatesh SK, et al. Performance of magnetic resonance elastography in primary sclerosing cholangitis. J Gastroenterol Hepatol. 2015 Dec 21. [Medline].
Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009 May 20. [Medline]. [Full Text].
Shi J, Li Z, Zeng X, Lin Y, Xie WF. Ursodeoxycholic acid in primary sclerosing cholangitis: meta-analysis of randomized controlled trials. Hepatol Res. 2009 May 7. [Medline].
Eckhauser FE, Colleti LM, Knol JA. The changing role of surgery for sclerosing cholangitis. Dig Dis. 1996 May-Jun. 14(3):180-91. [Medline].
Graziadei IW, Wiesner RH, Batts KP, et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999 Apr. 29(4):1050-6. [Medline].
Graziadei IW, Wiesner RH, Marotta PJ, et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. 1999 Nov. 30(5):1121-7. [Medline].
Lian L, Menon KV, Shen B, Remzi F, Kiran RP. Inflammatory bowel disease complicated by primary sclerosing cholangitis and cirrhosis: is restorative proctocolectomy safe?. Dis Colon Rectum. 2012 Jan. 55(1):79-84. [Medline].
Yimam KK, Bowlus CL. Diagnosis and classification of primary sclerosing cholangitis. Autoimmun Rev. 2014 Apr-May. 13 (4-5):445-50. [Medline].