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OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Primary sclerosing cholangitis

Gastroenterology and hepatology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Time-critical presentation

Fever, rigors, right-upper-quadrant pain, worsening jaundice, hypotension or confusion in PSC suggests bacterial cholangitis behind a relevant stricture. Obtain cultures, start local intravenous antibacterials and arrange urgent hepatobiliary and endoscopic assessment for drainage; resuscitation must not await MRCP. Haematemesis, ascites, encephalopathy or kidney injury signals hepatic decompensation. Rapidly progressive jaundice, weight loss, a new dominant or relevant stricture, gallbladder mass or rising cholestasis requires urgent specialist cancer evaluation because cholangiocarcinoma can mimic a benign PSC flare.

Overview

Diagnose primary sclerosing cholangitis non-invasively, recognise bacterial or malignant obstruction and coordinate inflammatory bowel, cancer and transplant surveillance.

PSC causes progressive inflammation and fibrosis around medium and large bile ducts. Cholangiography typically shows short multifocal narrowings alternating with relatively preserved or dilated segments, but imaging severity and symptoms correlate poorly. Biochemistry is usually cholestatic, yet ALP can fluctuate or occasionally be normal. The disease affects men more often and frequently accompanies ulcerative colitis or Crohn colitis. Other immune-mediated disorders may coexist, but classic autoantibodies are non-specific and do not diagnose PSC.

MRCP avoids instrumentation and gives a panoramic duct assessment, making it the usual first diagnostic study. ERCP introduces pancreatitis, bleeding, cholangitis and perforation risk, so it should answer a defined therapeutic or tissue question. A clinically relevant stricture is one that causes obstruction or concern, not merely the narrowest segment on an image. Brush cytology, fluorescence in-situ hybridisation where commissioned, intraductal sampling and repeat imaging may be combined in a hepatopancreatobiliary multidisciplinary pathway because no single negative sample fully excludes cholangiocarcinoma.

Practice

Two practice questions

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Gastroenterology and hepatologyOriginal SBA

Initial duct imaging

A patient with ulcerative colitis has persistent cholestatic liver tests and ultrasound shows no stone. Which investigation is preferred to map suspected PSC initially?

Choose one answer, then submit
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Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • BSG and UK-PSC guidelineUK diagnosis, MRCP, therapeutic ERCP, malignancy, IBD and transplant guidance.
  • Gut full UK-PSC guidelinePrimary professional guidance with evidence grades and CA19-9 limitations.
  • NICE NG12 suspected cancer referralEscalation framework for jaundice and hepatobiliary cancer concern.
  • BSG liver biopsy guidelineSafe histological assessment for small-duct and overlap phenotypes.
  • BNF cholestyramine monographCurrent administration, interaction and adverse-effect safeguards for itch treatment.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom

Long-term care spans liver, ducts and bowel. Surveillance strategies vary because evidence is imperfect: BSG/UK-PSC supports annual clinical review and imaging-oriented vigilance, while CA19-9 is not a stand-alone screening test. Coexistent colitis carries a distinct colorectal neoplasia risk and requires regular expert colonoscopy. Gallbladder polyps or masses need hepatobiliary review. Liver transplantation is the only established intervention for advanced global disease, and referral should account for recurrent sepsis and disabling itch as well as synthetic failure.

Key points

  • PSC is a chronic fibroinflammatory cholangiopathy producing multifocal stricturing and segmental dilatation of intrahepatic or extrahepatic bile ducts.
  • Most people have or later develop inflammatory bowel disease, commonly a colitis phenotype whose activity can be clinically quiet despite increased colorectal cancer risk.
  • Magnetic resonance cholangiopancreatography is the preferred diagnostic duct map; ERCP is reserved for tissue sampling or therapy after expert review.
  • A normal MRCP does not exclude small-duct PSC when cholestasis and compatible biopsy findings persist.
  • IgG4-related sclerosing cholangitis, secondary obstruction, ischaemic injury, infection, surgery and drug injury must be excluded before calling the process primary.
  • No medicine has convincingly altered the natural history for all patients, and routine high-dose ursodeoxycholic acid is not recommended.
  • New jaundice or deterioration can reflect stones, bacterial cholangitis, a treatable relevant stricture or cholangiocarcinoma rather than inevitable disease progression.
  • CA19-9 has insufficient diagnostic accuracy for screening alone; it can support but never establish cholangiocarcinoma, and some people do not express the antigen.

Aetiology

01

Immune and genetic susceptibility

PSC reflects polygenic immune susceptibility with dysregulated biliary inflammation; no single autoantibody or inherited variant is diagnostic.

02

Inflammatory bowel disease association

Most patients have or later develop IBD, commonly a colitis phenotype that may be clinically quiet despite important cancer risk.

03

Gut-biliary environmental interaction

Microbial products, barrier function and bile-acid signalling are proposed contributors, but the initiating cause remains incompletely defined.

Pathophysiology

  1. 1
    Chronic duct inflammation

    Immune-mediated injury affects intrahepatic and extrahepatic bile-duct epithelium in a patchy distribution with alternating strictures and dilatation.

  2. 2
    Concentric fibrosis and stricturing

    Repeated injury produces multifocal fibrotic narrowing with intervening dilatation, impairing drainage and creating dominant symptomatic segments.

  3. 3
    Cholestasis and biliary cirrhosis

    Retained bile drives hepatocyte injury, infection susceptibility and progressive portal fibrosis culminating in cirrhosis and liver failure.

Clinical features and red flags

Silent cholestatic disease

Persistent ALP and gamma-GT elevation is discovered in a person with inflammatory bowel disease despite little itch, pain or jaundice.

Chronic cholestatic phenotype

Pruritus, fatigue, fluctuating jaundice and right-upper-quadrant discomfort accompany multifocal duct narrowing without an acute septic syndrome.

Acute bacterial cholangitisRed flag

Fever or rigors with pain, jaundice, hypotension or confusion implies infected obstruction and needs immediate antibiotics and drainage assessment.

Possible cholangiocarcinomaRed flag

New persistent jaundice, weight loss, a changing stricture, gallbladder lesion or unexpectedly progressive cholestasis requires urgent HPB multidisciplinary investigation.

Small-duct disease

Cholestatic tests and compatible liver histology occur despite a normal high-quality cholangiogram, after other small-duct causes have been excluded.

Portal or hepatic decompensationRed flag

Thrombocytopenia, splenomegaly, ascites, variceal bleeding, encephalopathy or sarcopenia indicates advanced disease and prompts transplant-level review.

Investigations

  1. 01
    Liver biochemical and synthetic profileFirst step
    Why
    Characterise cholestasis and recognise deterioration.
    Interpretation and limitations
    Trend ALP, gamma-GT, bilirubin, aminotransferases, albumin and INR. A sudden bilirubin rise or inflammatory response suggests obstruction, infection, drug injury or cancer rather than simple linear progression.
  2. 02
    Magnetic resonance cholangiopancreatography
    Why
    Demonstrate multifocal intrahepatic and extrahepatic duct changes non-invasively.
    Interpretation and limitations
    Short annular strictures and intervening normal or ectatic ducts support large-duct PSC. A focal changing lesion, shouldering or upstream dilatation needs expert HPB review; technically poor normal imaging may require repetition.
  3. 03
    Hepatobiliary ultrasonography
    Why
    Assess gallbladder, proximal duct dilation, portal features and focal lesions.
    Interpretation and limitations
    Ultrasound complements rather than replaces MRCP. A polyp, mass, stone, ascites or new dilation changes urgency and may lead to cross-sectional cancer imaging.
  4. 04
    Serum IgG4 and mimic screen
    Why
    Identify a potentially steroid-responsive alternative and other secondary cholangiopathies.
    Interpretation and limitations
    Raised IgG4 supports but does not alone prove IgG4-related disease; pancreatic imaging, other organ involvement and histology may be needed. Review operations, critical illness, infection and medicines.

Differential diagnosis

01

IgG4-related cholangitis

Pancreatic enlargement, other IgG4-related organ disease and compatible serology or histology suggest a steroid-responsive mimic, but malignancy still requires exclusion.

02

Secondary sclerosing cholangitis

Biliary surgery, critical-illness ischaemia, recurrent infection or toxic injury provides a defined cause for a similar stricturing duct map.

03

Cholangiocarcinoma

Rapid jaundice, weight loss, rising cholestasis or a new irregular focal stricture requires specialist imaging and tissue planning for malignant obstruction.

Management

01DiagnosisConfirm PSC without unnecessary instrumentationFirst stepPersistent cholestasis or an IBD-associated liver-test abnormality raises a cholangiopathy.+
  1. 1Review medicines, infection, surgery and IBD history, measure IgG4 and obtain ultrasound to exclude an obvious mechanical or secondary cause.
  2. 2Perform high-quality MRCP and have a hepatobiliary radiologist assess distribution, strictures, gallbladder and any malignant feature.
  3. 3Reserve ERCP for a defined sampling or therapeutic problem, and use liver biopsy when ducts are normal but small-duct PSC or overlap remains plausible.
  4. 4At diagnosis stage fibrosis, investigate colitis with ileocolonoscopy and create a documented liver, biliary and bowel surveillance plan.
02Septic obstructionTreat cholangitis and restore drainageFever, rigors or sepsis accompanies worsening jaundice or a relevant stricture.+

Complications

01

Bacterial cholangitis

A tight stricture and stagnant bile permit ascending infection, causing fever, jaundice and sepsis that may require therapeutic ERCP.

02

Hepatobiliary and colorectal cancer

PSC increases cholangiocarcinoma and gallbladder neoplasia risk, while associated colitis carries heightened colorectal cancer risk despite modest bowel symptoms.

03

Cirrhosis and liver failure

Progressive biliary fibrosis causes portal hypertension, ascites, varices and eventual transplant need, sometimes despite fluctuating liver tests.

Monitoring and follow-up

  • Review ALP, bilirubin, aminotransferases, albumin, INR, platelets, weight, itch and cholangitis episodes at intervals based on stage and recent change.
  • Arrange periodic ultrasound or MR-based imaging according to the current UK-PSC plan, urgently repeating cross-sectional assessment for new persistent jaundice or pain.
  • Track every ERCP stent, cytology result and planned removal or exchange on a fail-safe list because forgotten prostheses can cause sepsis.
  • Ensure colonoscopic surveillance is performed at the high-risk interval for PSC-associated colitis and coordinate dysplasia findings in an IBD multidisciplinary team.
  • For cirrhosis provide HCC and variceal surveillance, bone and nutrition assessment, vaccinations and early transplant discussion.
  • Document patient-held emergency advice for fever, rigors, dark urine, pale stool, worsening jaundice or hypotension and a direct route to acute review.

Special situations

ERCP is a treatment test

MRCP establishes the duct pattern; invasive cholangiography should usually carry a clear intention to sample or improve drainage.

Quiet bowel still carries risk

PSC-associated colitis can be mild symptomatically yet confer high neoplasia risk, so surveillance cannot depend on flare frequency.

CA19-9 is contextual

Cholangitis and obstruction elevate the marker and non-secretors remain low; trends support an MDT decision but never settle it.

Small ducts can hide

Normal cholangiography with persistent cholestasis does not close the diagnosis when expert biopsy demonstrates compatible small-duct injury.

Transplant need is multidimensional

Recurrent sepsis or relentless itch can justify referral even before bilirubin and prognostic scores reach conventional end-stage thresholds.

Common pitfalls

  1. 01

    Sending every newly diagnosed PSC patient directly to diagnostic ERCP despite adequate MRCP and no therapeutic question.

  2. 02

    Treating a new relevant stricture as benign disease progression without coordinated cholangiocarcinoma sampling.

  3. 03

    Using a normal CA19-9 result to exclude biliary cancer or an elevated result to diagnose it.

  4. 04

    Omitting ileocolonoscopy because the patient denies bowel symptoms and thereby missing silent associated colitis.

  5. 05

    Prescribing high-dose UDCA and presenting improved ALP as proven prevention of progression.

  6. 06

    Giving antibiotics repeatedly for cholangitis without ensuring duct drainage and a plan for any temporary stent.

PSC with colitis requires high-quality regular colonoscopic surveillance from diagnosis under the current BSG IBD pathway, even when bowel symptoms are minimal.
  • Early transplant referral is appropriate for decompensation, recurrent bacterial cholangitis, intractable pruritus or selected cancer pathways, not only a high numerical score.
  • 05
    Endoscopic retrograde cholangiopancreatography
    Why
    Sample or decompress a clinically relevant stricture.
    Interpretation and limitations
    Undertake after HPB planning with prophylaxis and drainage intent. Brush cytology may be falsely negative, so discordant clinical suspicion warrants repeat, advanced sampling or surgical evaluation.
  • 06
    Colonoscopy with segmental surveillance biopsies
    Why
    Detect associated colitis and dysplasia.
    Interpretation and limitations
    Perform ileocolonic assessment at PSC diagnosis even without bowel symptoms. Once colitis is present, follow the current annual or locally specified high-risk BSG surveillance pathway with excellent preparation and expert imaging.
  • 07
    Liver biopsy
    Why
    Diagnose small-duct PSC or investigate AIH overlap and other parenchymal disease.
    Interpretation and limitations
    Periductal onion-skin fibrosis is characteristic but insensitive. Ductopenia and biliary injury need expert correlation; biopsy is not routinely necessary when MRCP is diagnostic.
  • 08
    CA19-9 with cross-sectional imaging
    Why
    Support investigation when cholangiocarcinoma is clinically suspected.
    Interpretation and limitations
    Elevation can occur in benign cholangitis and obstruction and absence does not exclude cancer, especially in non-secretors. Interpret only within imaging, drainage status and HPB review.
    • 1
    Obtain cultures and sepsis bloods, give IV fluid and organ support, and start local biliary-sepsis antibacterials immediately.
  • 2Contact the therapeutic endoscopy and HPB teams early and image rapidly without allowing elective MRCP access to delay source control.
  • 3At ERCP drain the obstructed system and obtain cytology or biopsies when a suspicious stricture is present, using the least traumatic effective intervention.
  • 4Review culture results, remove or exchange any temporary stent on schedule and reassess for cancer if cholestasis does not resolve.
    • 03Cancer concernInvestigate a changing stricture through the HPB MDTProgressive jaundice, weight loss or new imaging abnormality raises cholangiocarcinoma concern.+
    1. 1Obtain contrast-enhanced liver and biliary imaging and discuss before duct instrumentation so staging and sampling are coordinated.
    2. 2Use CA19-9 only as supporting context and treat infection or obstruction that can falsely elevate it.
    3. 3Arrange ERCP brushings, biopsies or advanced tissue techniques through the MDT, recognising that a negative first cytology result has limited sensitivity.
    4. 4EscalationRepeat or escalate sampling when suspicion persists and refer promptly to specialist resection, transplant-oncology or palliative pathways as appropriate.
    04Long-term careLink liver, bowel and transplant surveillancePSC is established and no acute obstruction requires intervention.+
    1. 1Review symptoms, liver tests, fibrosis and portal features at least annually, with imaging and gallbladder assessment according to the current UK-PSC pathway.
    2. 2Deliver regular high-risk colonoscopic surveillance for PSC-associated colitis and ensure bowel inflammation is actively treated despite minimal symptoms.
    3. 3Manage itch, nutrition, bone and fat-soluble vitamin risk and cirrhosis complications without claiming unproven disease modification from UDCA.
    4. 4Refer early for transplant assessment when decompensation, recurrent cholangitis, progressive synthetic dysfunction or intolerable pruritus emerges.
    Key medicines and prescribing safety3 treatments · regimens, roles and cautions+
    Treats bacterial infection accompanying obstructed PSC ducts while definitive endoscopic or radiological source control is arranged.

    Intravenous antibacterial therapy for acute cholangitis

    Start the hospital's current biliary-sepsis regimen immediately after cultures when feasible, adjusting for allergy, renal function, previous cultures and healthcare exposure; review promptly after drainage and microbiology results.

    Antibiotics cannot compensate for an undrained infected system. Review Clostridioides difficile risk, interactions and local resistance, and avoid indefinite prophylaxis without a specialist recurrent-cholangitis plan.

    May reduce cholestatic itch but has no proven effect on PSC fibrosis, stricturing or cancer risk.

    Cholestyramine for pruritus

    Use the licensed BNF regimen as a specialist or primary-care supervised trial, beginning at a tolerable dose and taking it at least four to six hours apart from essential oral medicines.

    Constipation, bloating and poor palatability are common. It can reduce absorption of anticoagulants, vitamins and other treatment; exclude a new obstructing stricture before attributing worsening itch to chronic disease.

    May improve liver biochemistry in some people but has not reliably improved survival or prevented colorectal or biliary cancer in unselected PSC.

    Ursodeoxycholic acid

    Do not initiate routine high-dose UDCA as disease-modifying treatment for newly diagnosed PSC. Any existing or selected lower-dose use should be reviewed by an experienced hepatologist against current BSG guidance and individual biochemical goals.

    Biochemical improvement must not be presented as proof of altered natural history. Avoid high-dose regimens and do not let treatment postpone evaluation of jaundice, cholangitis or a malignant stricture.