Primary Biliary Cholangitis (PBC)
Summary
Primary Biliary Cholangitis (PBC), formerly known as Primary Biliary Cirrhosis, is a chronic autoimmune liver disease characterised by progressive destruction of the intrahepatic small bile ducts, leading to cholestasis (impaired bile flow), fibrosis, and ultimately cirrhosis. It predominantly affects middle-aged women (9:1 Female:Male ratio). The hallmark is the presence of Anti-Mitochondrial Antibodies (AMA) in ~95% of patients. Common symptoms include fatigue and pruritus (itch), with elevated ALP (Alkaline Phosphatase) on liver function tests. Ursodeoxycholic Acid (UDCA) is the first-line treatment and slows disease progression in most patients. Liver transplantation is the definitive treatment for decompensated disease. [1,2]
Clinical Pearls
AMA is the Key Antibody: Anti-Mitochondrial Antibody (AMA, specifically AMA-M2) is highly specific for PBC (~95% positive). If AMA positive + Cholestatic LFTs = High probability of PBC.
Renamed! No Longer "Cirrhosis": PBC was renamed from "Primary Biliary Cirrhosis" because many patients are diagnosed before cirrhosis develops.
"The Itch is Terrible": Pruritus can be severe and debilitating, often worse at night. Treat with Cholestyramine first-line.
UDCA for All: All patients with PBC should be on Ursodeoxycholic Acid (UDCA). It improves survival and slows progression.
Demographics
- Sex: Female >> Male (9:1).
- Age: Typically 40-60 years at diagnosis. Can occur 30-70 years.
- Geography: Higher prevalence in Northern Europe and North America.
Incidence
- Prevalence: ~40 per 100,000 population.
- Increasing detection: More cases diagnosed earlier due to incidental LFT abnormalities.
Associations (Other Autoimmune Conditions)
| Associated Condition | Notes |
|---|---|
| Sjögren's Syndrome | Dry eyes, Dry mouth. Common (~70%). |
| Autoimmune Thyroiditis (Hashimoto's) | ~20%. |
| Rheumatoid Arthritis | ~10%. |
| Systemic Sclerosis (CREST Syndrome) | ~5%. |
| Coeliac Disease | ~5%. |
Mechanism
- Autoimmune Attack: Autoreactive T-lymphocytes target the mitochondrial pyruvate dehydrogenase complex (PDC-E2) on the biliary epithelial cells of small intrahepatic bile ducts.
- Bile Duct Destruction: Chronic granulomatous inflammation around and destroying interlobular bile ducts ("Florid Duct Lesion").
- Cholestasis: Reduced bile flow due to ductopenia (loss of bile ducts). Retention of bile acids in the liver.
- Hepatocyte Injury: Toxic bile acids damage hepatocytes.
- Fibrosis: Chronic inflammation leads to progressive fibrosis.
- Cirrhosis: End-stage – Portal hypertension, Liver failure.
Histological Stages (Ludwig / Scheuer)
| Stage | Description |
|---|---|
| Stage I | Portal inflammation. Florid Duct Lesion (Granulomatous destruction of bile ducts). |
| Stage II | Periportal fibrosis. Bile ductular proliferation. |
| Stage III | Bridging fibrosis (Porto-portal). |
| Stage IV | Cirrhosis. |
| Condition | Key Features |
|---|---|
| Primary Biliary Cholangitis (PBC) | Middle-aged woman. AMA positive (95%). Small duct destruction. Pruritus. |
| Primary Sclerosing Cholangitis (PSC) | Usually male. Associated with Ulcerative Colitis (70%). Large/Medium duct disease. MRCP: "Beaded" bile ducts. AMA Negative. p-ANCA may be positive. |
| Drug-Induced Cholestasis | Drug history (e.g., Co-Amoxiclav, OCP). Resolves on drug withdrawal. |
| Biliary Obstruction (Mechanical) | Dilated bile ducts on USS/CT. Gallstones, Stricture, Tumour. |
| Overlap Syndrome (PBC-AIH) | Features of both PBC and Autoimmune Hepatitis. May need steroids. |
| IgG4-Related Cholangitis | Part of IgG4-related disease. Elevated serum IgG4. Responds to steroids. |
Symptoms
| Symptom | Notes |
|---|---|
| Asymptomatic | Many diagnosed incidentally on routine LFTs (raised ALP). ~50% at diagnosis. |
| Fatigue | Very common (70-80%). Often debilitating. Poorly correlates with disease severity. |
| Pruritus (Itch) | ~50%. Can be severe and intractable. Worse at night. Due to bile acid retention. |
| Jaundice | Late feature. Indicates advanced disease. |
| Xanthelasma / Xanthomata | Cholesterol deposits (skin, tendons). Due to hyperlipidaemia from cholestasis. |
| Dry Eyes / Dry Mouth | Sjögren's Syndrome overlap. |
| Right Upper Quadrant Discomfort | Hepatomegaly. |
Signs
| Sign | Notes |
|---|---|
| Hepatomegaly | Common. |
| Splenomegaly | If portal hypertension develops. |
| Xanthelasma | Yellowish plaques around eyelids. |
| Skin Hyperpigmentation | "Bronzed" appearance from melanin deposition. |
| Excoriations | Scratch marks from pruritus. |
| Signs of Cirrhosis (Late) | Ascites, Spider naevi, Palmar erythema, Peripheral oedema. |
Blood Tests
| Test | Findings |
|---|---|
| LFTs | Raised ALP (Alkaline Phosphatase) – Hallmark of cholestasis. GGT also raised. Bilirubin raised late. AST/ALT mildly elevated or normal. |
| Anti-Mitochondrial Antibody (AMA) | Positive in ~95% (Specifically AMA-M2 subtype). Highly specific for PBC. |
| ANA | May be positive (~30%). ANA +ve / AMA -ve may be "AMA-negative PBC". |
| Immunoglobulins | IgM elevated (Characteristic of PBC). |
| Bilirubin | Elevated in advanced disease. Prognostic marker. |
| Cholesterol | Often elevated (hyperlipidaemia). |
Imaging
| Imaging | Purpose |
|---|---|
| Liver Ultrasound | Rule out biliary obstruction (dilated ducts). May show hepatomegaly, coarse liver echotexture (cirrhosis). |
| MRCP | If uncertainty about large duct disease (to differentiate from PSC). Normal in PBC. |
| Fibroscan / Transient Elastography | Non-invasive assessment of liver fibrosis. |
Liver Biopsy
- Not always required for diagnosis if AMA +ve and cholestatic LFTs.
- Indications: AMA negative, Suspicion of Overlap Syndrome, To stage fibrosis.
- Histology: Florid Duct Lesion, Granulomas, Ductopenia, Fibrosis.
Diagnostic Criteria (AASLD / EASL)
Diagnosis established if ≥2 of 3:
- Elevated ALP (cholestatic pattern LFTs) for >6 months.
- AMA positive (≥1:40) or PBC-specific ANA (anti-sp100, anti-gp210).
- Liver biopsy consistent with PBC.
Management Algorithm
SUSPECTED PBC
(Middle-Aged Woman + Fatigue/Pruritus + Raised ALP)
↓
CHECK AMA + LFTs + Imaging
┌────────────────┴────────────────┐
AMA +ve AMA -ve
+ Cholestatic LFTs + Cholestatic LFTs
↓ ↓
PBC DIAGNOSED CONSIDER:
(Biopsy usually NOT required) - AMA-Negative PBC (Check PBC-specific ANA)
- Overlap Syndrome (AIH features)
- Liver Biopsy
- PSC (Do MRCP)
↓
ALL PATIENTS:
URSODEOXYCHOLIC ACID (UDCA)
13-15 mg/kg/day
(Improves LFTs, Slows Progression, Improves Survival)
↓
ASSESS RESPONSE AT 12 MONTHS
(Toronto / Paris Criteria)
┌────────────────┴────────────────┐
ADEQUATE RESPONSE INADEQUATE RESPONSE
(ALP less than 1.67x ULN, Bili Normal) (ALP >1.67x or Raised Bili)
↓ ↓
CONTINUE UDCA ADD SECOND-LINE THERAPY
+ Monitor annually - OBETICHOLIC ACID (OCA)
(LFTs, Fibroscan) (if no advanced cirrhosis)
- OR BEZAFIBRATE (Off-label)
↓
IF DECOMPENSATED CIRRHOSIS:
LIVER TRANSPLANT REFERRAL
↓
SYMPTOM MANAGEMENT
- PRURITUS: See below
- FATIGUE: No proven treatment. Address sleep, thyroid, anaemia.
- OSTEOPOROSIS: Bone density monitoring. Calcium + Vit D. Bisphosphonates.
- FAT-SOLUBLE VITAMIN DEFICIENCY (A, D, E, K): Supplement if cholestatic.
Ursodeoxycholic Acid (UDCA)
- Dose: 13-15 mg/kg/day.
- Mechanism: Reduces toxic hydrophobic bile acids, improves bile flow, has immunomodulatory effects.
- Efficacy: Improves LFTs in ~70%. Slows histological progression. Improves transplant-free survival.
- All patients should receive UDCA.
Second-Line Therapy (For UDCA Non-Responders)
| Agent | Notes |
|---|---|
| Obeticholic Acid (OCA) | FXR agonist. Add to UDCA if inadequate response. Contraindicated in decompensated cirrhosis (risk of worsening liver failure). Can cause pruritus. |
| Bezafibrate | Off-label. Improves LFTs and pruritus. Often used in Europe. |
Management of Pruritus
| Line | Treatment | Notes |
|---|---|---|
| 1st | Cholestyramine (4-16g/day) | Bile acid sequestrant. Take 2-4 hours away from other medications (binds drugs). |
| 2nd | Rifampicin (150-300mg BD) | Enzyme inducer. Monitor LFTs (hepatotoxicity risk). Very effective but use with caution. |
| 3rd | Naltrexone | Opioid antagonist. Off-label. |
| 4th | Sertraline | SSRI. Some evidence. |
| Refractory | Plasmapheresis / Liver Transplant | For intractable pruritus. |
Other Management
| Issue | Management |
|---|---|
| Osteoporosis | DEXA scan at diagnosis. Calcium + Vitamin D. Bisphosphonates if indicated. |
| Fat-Soluble Vitamin Deficiency | Supplement Vitamin A, D, E, K if cholestatic. |
| Hyperlipidaemia | Usually does not increase CV risk (different lipoprotein profile). Statins if CVD risk factors. |
| Sicca Symptoms (Sjögren's) | Artificial tears. Good oral hygiene. |
| Liver Transplantation | For decompensated cirrhosis, intractable pruritus, HCC. Excellent outcomes. Low recurrence. |
| Complication | Notes |
|---|---|
| Cirrhosis | End-stage. Portal hypertension, Ascites, Varices, Encephalopathy. |
| Hepatocellular Carcinoma (HCC) | Risk is lower than in viral hepatitis but still present in cirrhotic PBC. Surveillance USS 6-monthly. |
| Osteoporosis | Cholestasis impairs Vitamin D absorption. Increased fracture risk. |
| Fat-Soluble Vitamin Deficiency | Vitamins A, D, E, K. Can cause night blindness, bruising, neuropathy. |
| Pruritus (Severe) | Major impact on quality of life. |
| Associated Autoimmune Diseases | Sjögren's, Thyroiditis, RA, Coeliac. |
- With UDCA Response: Near-normal life expectancy.
- Without UDCA Response or No Treatment: Median survival ~10-15 years.
- Prognostic Markers: Bilirubin level (rising is poor), UDCA response, Fibrosis stage.
- Liver Transplant: Excellent survival (>90% at 5 years). Low recurrence rate (~15% at 10 years).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| EASL Clinical Practice Guidelines for PBC | EASL (2017) | UDCA 13-15mg/kg. Second-line OCA. Transplant for decompensated. |
| AASLD Guidance | AASLD | Similar. Emphasise identifying non-responders. |
What is PBC?
PBC is a condition where your body's immune system mistakenly attacks the small bile ducts in your liver. Bile normally flows from the liver to help digest fats. When the ducts are damaged, bile builds up in the liver, causing inflammation and scarring over time.
Why did I get it?
We don't know exactly why, but it is an autoimmune disease – your immune system has started attacking your own body. It is not caused by alcohol or infection.
What are the symptoms?
Many people have no symptoms initially. Common symptoms include tiredness (fatigue) and itching (pruritus). In later stages, yellowing of the skin (jaundice) can occur.
How is it treated?
You will be given a medication called Ursodeoxycholic Acid (UDCA), a bile acid that protects your liver and slows down the disease. Most people respond well and have a good outlook. If the disease progresses despite treatment, liver transplantation is very successful.
Primary Sources
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Primary biliary cholangitis. J Hepatol. 2017;67(1):145-172. PMID: 28427765.
- Lindor KD, et al. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. PMID: 30070375.
Common Exam Questions
- Key Antibody: "What is the characteristic autoantibody in PBC?"
- Answer: Anti-Mitochondrial Antibody (AMA, specifically AMA-M2). Positive in ~95%.
- LFT Pattern: "What pattern of LFTs is seen in PBC?"
- Answer: Cholestatic – Elevated ALP (and GGT). Bilirubin rises late.
- First-Line Treatment: "First-line treatment for PBC?"
- Answer: Ursodeoxycholic Acid (UDCA) 13-15 mg/kg/day.
- Pruritus Treatment: "First-line treatment for pruritus in PBC?"
- Answer: Cholestyramine.
Viva Points
- PBC vs PSC: Know the key differences (AMA, IBD association, duct size, MRCP findings).
- UDCA Non-Responders: Discuss second-line options (OCA, Bezafibrate) and transplant referral.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.