Overview
Primary Sclerosing Cholangitis (PSC)
1. Clinical Overview
Summary
Primary Sclerosing Cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterised by inflammation, fibrosis, and stricturing of both intrahepatic and extrahepatic bile ducts. The aetiology is unknown but likely involves immune-mediated mechanisms in genetically susceptible individuals. PSC has a strong association with Inflammatory Bowel Disease (IBD), particularly Ulcerative Colitis (UC) (~70-80% of PSC patients have IBD). Patients may present with fatigue, pruritus, jaundice, or be diagnosed incidentally through abnormal liver function tests (Raised ALP). Imaging shows characteristic "Beads-on-a-string" appearance of bile ducts on MRCP. There is no proven medical therapy to slow disease progression. Complications include recurrent cholangitis, biliary strictures, cirrhosis, and a significantly increased risk of cholangiocarcinoma (~10-15% lifetime) and colorectal cancer (If IBD present). Liver transplantation is the only curative treatment for end-stage disease. [1,2,3]
Clinical Pearls
"PSC + UC = Think of Both": ~70-80% of PSC patients have IBD (Usually UC). All PSC patients need colonoscopy. All UC patients with abnormal LFTs need PSC screening.
"Beads-on-a-String": Classic MRCP finding – Multifocal strictures with intervening dilations of bile ducts.
"No Medical Treatment Works": Unlike PBC, There is no proven medical therapy to alter PSC disease progression. Ursodeoxycholic acid (UDCA) improves LFTs but NOT outcomes.
"Cholangiocarcinoma Risk": Lifetime risk ~10-15%. Difficult to diagnose. Dominant stricture = Cancer until proven otherwise.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Age | Typically diagnosed 30-40 years. |
| Sex | Male > Female (2:1). |
| Prevalence | ~1-16 per 100,000. Higher in Northern Europe. |
| Association with IBD | ~70-80% have IBD (Usually UC). Only ~5% of UC patients have PSC. |
Risk Factors
| Risk Factor | Notes |
|---|---|
| Inflammatory Bowel Disease | Particularly Ulcerative Colitis. |
| Genetic | HLA associations (HLA-B8, HLA-DR3, HLA-DR4). |
| Male Sex | |
| Smoking | Paradoxically may be protective. |
3. Pathophysiology
Aetiology (Unknown)
- Immune-Mediated: Autoimmune component, Though not classic autoimmune disease (No proven immunosuppression benefit).
- Genetic Susceptibility: HLA associations.
- Gut-Liver Axis: Hypothesis that enteric bacteria or toxins trigger hepatobiliary inflammation (Link with IBD).
Pathological Process
- Bile Duct Inflammation: Periductal lymphocytic infiltration.
- Fibrosis: "Onion-skin" periductal fibrosis (Classic histology).
- Strictures: Multifocal strictures of intrahepatic and extrahepatic bile ducts.
- Cholestasis: Impaired bile flow.
- Secondary Biliary Cirrhosis: Chronic cholestasis leads to cirrhosis.
4. Clinical Presentation
Symptoms
| Symptom | Notes |
|---|---|
| Asymptomatic | Up to ~50% diagnosed incidentally (Abnormal LFTs). |
| Fatigue | Common. Non-specific. |
| Pruritus | Due to cholestasis. May be severe and debilitating. |
| Jaundice | Intermittent (Strictures) or Progressive (Advanced disease). |
| Right Upper Quadrant Pain | Intermittent. May worsen with cholangitis. |
| Symptoms of IBD | Diarrhoea, Blood in stool (If UC present). |
Examination Findings
| Finding | Notes |
|---|---|
| Hepatomegaly | May be present. |
| Splenomegaly | If portal hypertension. |
| Jaundice | Advanced disease. |
| Excoriations | From scratching (Pruritus). |
| Stigmata of Chronic Liver Disease | Spider naevi, Palmar erythema (If cirrhotic). |
Episodes of Cholangitis
Fever, RUQ pain, Jaundice (Charcot's triad).
Common presentation.
Triggered by dominant strictures and bacterial superinfection.
Common presentation.
5. Investigations
Biochemistry
| Test | Findings |
|---|---|
| Alkaline Phosphatase (ALP) | Elevated (Often 3-10x normal). Hallmark. |
| GGT | Elevated. |
| Bilirubin | Initially normal. Elevated in advanced disease or during cholangitis. |
| AST / ALT | Mildly elevated (Usually less than 300). |
Autoantibodies
| Antibody | Notes |
|---|---|
| pANCA (Atypical) | Positive in ~65-80%. Not specific. |
| AMA | Negative (Positive in PBC). |
| ANA, SMA | May be positive (Non-specific). |
Imaging (Key Diagnostic Test)
| Modality | Findings |
|---|---|
| MRCP (Magnetic Resonance Cholangiopancreatography) | Gold Standard. "Beads-on-a-String": Multifocal strictures and dilations of intrahepatic and extrahepatic bile ducts. Pruning of peripheral ducts. |
| ERCP | Historically gold standard. Now reserved for therapeutic intervention (Stricture dilatation, Stenting, Cytology). Risk of cholangitis. |
Liver Biopsy
| Notes |
|---|
| Often NOT required for diagnosis (MRCP usually sufficient). |
| Histology: "Onion-skin" periductal fibrosis. Bile duct damage. Ductopenia. |
| Useful if small duct PSC suspected (Normal cholangiogram but cholestatic LFTs + histological features). |
Colonoscopy
| Notes |
|---|
| All patients with PSC should have colonoscopy (To screen for IBD, Even if asymptomatic). |
| Annual surveillance colonoscopy if IBD present (High colorectal cancer risk). |
6. Differential Diagnosis
| Condition | Key Features |
|---|---|
| PSC | IBD association, Multifocal strictures on MRCP, AMA negative, pANCA positive. |
| Primary Biliary Cholangitis (PBC) | Middle-aged women, AMA positive, Interlobular bile duct destruction, NO strictures on MRCP. |
| Secondary Sclerosing Cholangitis | History of choledocholithiasis, Surgical injury, Ischaemia, IgG4-related disease. |
| Cholangiocarcinoma | Malignant biliary stricture – May be difficult to distinguish from PSC stricture. Dominant stricture requires investigation. |
| IgG4-Related Cholangitis | Elevated serum IgG4. Responds to steroids. PSC mimic. |
7. Management
Management Algorithm
SUSPECTED PSC
(Cholestatic LFTs, IBD, Pruritus)
↓
CONFIRM DIAGNOSIS
- LFTs (ALP elevated)
- AMA negative (Rules out PBC)
- MRCP ("Beads-on-a-string")
↓
BASELINE ASSESSMENT
- Colonoscopy (Screen for IBD)
- FibroScan / FIB-4 (Fibrosis stage)
- Bloods: LFTs, Bilirubin, Albumin, INR
↓
NO PROVEN DISEASE-MODIFYING TREATMENT
- UDCA: Improves LFTs. Does NOT improve outcomes.
(Some centres use UDCA 13-15mg/kg/day)
- High-dose UDCA (>25mg/kg) may be harmful – Avoid.
↓
SYMPTOM MANAGEMENT
┌──────────────────────────────────────────────────────────┐
│ **PRURITUS** │
│ - Cholestyramine (First-line) │
│ - Rifampicin (Second-line) │
│ - Sertraline │
│ - Naltrexone │
│ │
│ **FAT-SOLUBLE VITAMIN DEFICIENCY** │
│ - Replace A, D, E, K if cholestasis severe │
│ │
│ **OSTEOPOROSIS** │
│ - DEXA scan. Calcium + Vitamin D. Bisphosphonates. │
└──────────────────────────────────────────────────────────┘
↓
DOMINANT STRICTURE
- High suspicion for Cholangiocarcinoma
- ERCP with Brushings / Cytology
- Consider EUS-FNA
- Balloon dilatation ± Stenting (If benign)
↓
SURVEILLANCE
┌──────────────────────────────────────────────────────────┐
│ **CHOLANGIOCARCINOMA SURVEILLANCE** │
│ - No proven strategy. Annual MRCP ± USS ± CA19-9. │
│ - Dominant stricture = Urgent ERCP + Brushings. │
│ │
│ **COLORECTAL CANCER SURVEILLANCE (If IBD)** │
│ - **Annual Colonoscopy** (High CRC risk with PSC + UC). │
│ │
│ **GALLBLADDER POLYPS** │
│ - Cholecystectomy if polyp ≥8mm (High cancer risk). │
└──────────────────────────────────────────────────────────┘
↓
END-STAGE LIVER DISEASE
- Refer for **Liver Transplantation**
- Curative. 5-year survival >80%.
- PSC can recur in graft (~20-25%).
Treatment Summary
| Treatment | Notes |
|---|---|
| UDCA (Ursodeoxycholic Acid) | Improves LFTs. Does NOT improve survival, Symptom progression, or transplant-free survival in trials. High-dose (>25mg/kg) may be harmful. Some centres still prescribe low-dose. |
| Immunosuppression | NOT effective (Unlike PBC). |
| Antibiotics | For episodes of acute cholangitis. |
| ERCP | For dominant stricture dilatation/Stenting. Cytology to exclude cholangiocarcinoma. |
| Liver Transplant | Only curative treatment. Indicated for decompensated cirrhosis, Intractable pruritus, Recurrent cholangitis. |
8. Complications
| Complication | Notes |
|---|---|
| Cholangiocarcinoma | Lifetime risk ~10-15%. Often presents with dominant stricture. Prognosis poor. May contraindicate transplant (Unless strict criteria). |
| Recurrent Cholangitis | Bacterial superinfection of bile. Fever, RUQ pain, Jaundice. |
| Dominant Stricture | May cause cholestasis, Jaundice, Cholangitis. Needs ERCP. |
| Cirrhosis / Portal Hypertension | Variceal bleeding, Ascites, Encephalopathy. |
| Colorectal Cancer | If IBD present. Annual colonoscopy. |
| Gallbladder Cancer | Increased risk. Cholecystectomy for polyps ≥8mm. |
| Fat-Soluble Vitamin Deficiency | A, D, E, K. Due to cholestasis. |
| Osteoporosis | Due to cholestasis and malabsorption. |
9. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Median Survival (Without Transplant) | ~10-15 years from diagnosis. Variable. |
| Liver Transplant | 5-year survival >80%. Disease can recur in graft (~20-25%). |
| Cholangiocarcinoma | Poor prognosis. Often unresectable at diagnosis. |
| Mayo Risk Score / UK-PSC Score | Prognostic models using clinical and biochemical parameters. |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| PSC Management | EASL / BSG | MRCP for diagnosis. No proven medical therapy. Colonoscopy for all. Transplant for end-stage. |
Key Points
- UDCA Controversy: Improves biochemistry. No mortality benefit in trials. High-dose harmful.
- Surveillance Challenges: Cholangiocarcinoma surveillance is difficult. No proven effective strategy.
11. Patient and Layperson Explanation
What is PSC?
Primary Sclerosing Cholangitis (PSC) is a disease where the bile ducts inside and outside the liver become scarred and narrowed. This blocks the flow of bile and damages the liver over time.
Who gets it?
It is more common in men and usually diagnosed in the 30s-40s. About 7-8 out of 10 people with PSC also have inflammatory bowel disease (Usually Ulcerative Colitis).
What are the symptoms?
- Many people have no symptoms at first.
- Tiredness.
- Itching (Pruritus).
- Jaundice (Yellow skin and eyes).
- Abdominal pain.
Is there a cure?
There is no medication that can stop PSC from progressing. Treatment focuses on managing symptoms and complications. Liver transplant is the only cure for advanced disease.
What are the risks?
- Cholangiocarcinoma (Bile duct cancer) – Higher risk with PSC. Regular monitoring is important.
- Bowel cancer – If you have IBD, You need regular colonoscopies.
- Liver failure – May require transplant.
12. References
Primary Sources
- Chapman R, 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. PMID: 31154395.
- Karlsen TH, et al. Primary sclerosing cholangitis. J Hepatol. 2017;67(6):1298-1323. PMID: 28802875.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267. PMID: 19501929.
13. Examination Focus
Common Exam Questions
- Association: "What is the most common extrahepatic association of PSC?"
- Answer: Inflammatory Bowel Disease (Ulcerative Colitis in ~70-80%).
- MRCP Finding: "What is the classic imaging finding on MRCP?"
- Answer: "Beads-on-a-String" – Multifocal strictures and dilations of bile ducts.
- Medical Treatment: "Is there a proven medical therapy for PSC?"
- Answer: No. UDCA improves LFTs but NOT outcomes. No disease-modifying drug.
- Cancer Risk: "What malignancy is significantly increased in PSC?"
- Answer: Cholangiocarcinoma (~10-15% lifetime risk).
Viva Points
- PSC vs PBC: PSC = Male, IBD, AMA negative, Duct strictures on MRCP. PBC = Female, AMA positive, Interlobular duct destruction (Histology), NO duct strictures.
- Dominant Stricture: Cancer until proven otherwise. ERCP + Brushings.
- Annual Colonoscopy: If IBD present – High CRC risk.
- Liver Transplant: Only cure. PSC can recur in graft.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.