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Primary Sclerosing Cholangitis

Sclerosing cholangitis is a chronic, fibrotizing and constrictive inflammation of the biliary ducts that progresses slowly and leads to cholestatic liver damage, to cirrhosis and in some patients to cholangiocarcinoma
E.g. in the Nordic countries, the prevalence of sclerosing cholangitis is particularly high and it is the most common indication for liver transplantation.

Prevalence 1-9/100 000 http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=783
More common in men than in women
Age at onset is 25-45 years but the disease is encountered in children as well.

60-80% of PSC patients have inflammatory bowel disease (IBD), most commonly ulcerative colitis. Respectively, 2-8% of patients with ulcerative colitis in turn are diagnosed with sclerosing cholangitis.
HLA associations, concomitant other autoimmune diseases and circulating antibodies suggest an autoimmune aetiology.
- No specific antibodies (pANCA, antinuclear or anti-smooth muscle antibodies)

Most patients are asymptomatic at the time of diagnosis; abnormal liver function test results (typically alkaline phosphatase) are detected incidentally.
Investigations
- See article Assessing a patient with an abnormal liver function test result Assessing a Patient with an Abnormal Liver Function Test Result
- Ultrasonography of the liver
- MRI of the liver is ordered at a lower threshold than normal on a patient with IBD Ulcerative Colitis Crohn's Disease who has fluctuation in the liver test results.
Cholangitis with fever is possible. Weight loss and jaundice are symptoms of a late phase.
Diagnosis is based on abnormal findings on the examination of the biliary tract.
- MR cholangiography is used as the first-line study.
- Endoscopic retrograde cholangiography (ERCP) is the "golden standard": confirmation of the diagnosis, samples from the biliary tract, concurrent dilatation and stenting of the biliary ducts if needed.
- Liver biopsy: in case of non-specific histology, in the differential diagnostics of diseases of the small biliary ducts or other chronic hepatitides, gradation of the inflammation and fibrosis
Colonoscopy to detect silent colitis is indicated in all patients.
Autoimmune cholangitis is a rarer diagnostic alternative.
- The patient often has other autoimmune diseases; IBD in less than 10%
- Diagnosis: MRI; serum IgG4 increased; typical histology in the papilla/bile ducts, IgG4-positive plasma cells
- Good response to glucocorticoid therapy

There is no evidence on the effect of any treatment.
Ursodeoxycholic acid is commonly used, 15-20 mg/kg/day divided into 2 doses. When started in time, ursodeoxycholic acid slows the progress of inflammation and corrects liver biochemistry to a certain extent but the evidence on clinical benefit is scarce.
Metronidazole (600-800 mg/day) may retard the progression of the disease. The drug is used if there is no response to ursodeoxycholic acid.
Biliary strictures can be dilatated and stented endoscopically (ERCP).
Management of complications
- Cholangitides are treated with antimicrobials.
- Treatment of itching associated with cholestasis: antihistamines, cholestyramine, rifampicin
- Cirrhosis: treatment of e.g. portal hypertension and ascites; see Cirrhosis of the Liver.
Sclerosing cholangitis is the most common indication for liver transplantation in the Nordic countries. The indications include
- precancerous findings, such as increased concentrations of tumour markers (CA19-9, CEA) and suspicious cytology
- rapid progression of symptoms, abnormal laboratory parameters or changes found in ERC
- recurrent febrile cholangitides
- complications of liver cirrhosis.

Regular follow-up takes place in the specialized care.
- Laboratory test every 3 to 6 months (tests reflecting the liver function, tumour markers)
- Imaging studies according to the situation (MRI, ERCP, CT)
- Annual follow-up colonoscopy in patients with IBD (the risk of bowel dysplasia is also increased)

Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021;70(10):1989-2003 [PubMed]
Barner-Rasmussen N, Pukkala E, Jussila A, et al. Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland. Scand J Gastroenterol 2020;55(1):74-81[PubMed]
Chapman MH, Thorburn D, Hirschfield GM, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019;68(8):1356-1378[PubMed]
Färkkilä M. [Primary sclerosing cholangitis (PSC)]. In: Färkkilä M, Heikkinen M, Isoniemi H, Puolakkainen P (eds.). [Gastroenterology and hepatology]. Duodecim Publishing Company Ltd 2018. Available in Finnish.
Karlsen TH, Folseraas T, Thorburn D, et al. Primary sclerosing cholangitis - a comprehensive review. J Hepatol 2017;67(6):1298-1323[PubMed]