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 bile ducts (small bile ducts within the liver). It predominantly affects middle-aged women and is associated with other autoimmune conditions (Sjögren's, thyroid disease). The hallmark is the presence of Anti-Mitochondrial Antibodies (AMA), positive in ~95% of patients. Patients often present with fatigue and pruritus (itching), though many are asymptomatic and detected incidentally via raised alkaline phosphatase. First-line treatment is Ursodeoxycholic Acid (UDCA), which slows disease progression. Without treatment, PBC progresses to cirrhosis and liver failure; liver transplantation is curative.
Key Facts
- Definition: Autoimmune destruction of intrahepatic bile ducts
- Demographics: Middle-aged women (F:M = 9:1)
- Antibody: Anti-Mitochondrial Antibody (AMA) — 95% specific
- Symptoms: Pruritus, Fatigue, Xanthelasma; Often asymptomatic
- Labs: Raised ALP, GGT; IgM raised; Bilirubin rises late
- Treatment: Ursodeoxycholic Acid (UDCA)
Clinical Pearls
"AMA = PBC": Anti-Mitochondrial Antibodies (especially M2 subtype) are highly specific for PBC.
"Pruritus Before Jaundice": Severe itching often precedes any signs of liver failure by years.
"Not Cirrhosis at Diagnosis": The name was changed from "Primary Biliary Cirrhosis" because most patients are diagnosed before cirrhosis develops.
"UDCA Early = Better Outcomes": Early treatment with Ursodeoxycholic Acid improves survival.
Prevalence
- 20-50 per 100,000
Demographics
- F:M = 9:1
- Peak: 40-60 years
- Rare in men and under 25
Associations
| Condition | Notes |
|---|---|
| Sjögren's syndrome | Dry eyes, Dry mouth |
| Rheumatoid arthritis | |
| Autoimmune thyroiditis | |
| Coeliac disease | |
| Systemic sclerosis | CREST variant |
Mechanism
- T-cell mediated autoimmune destruction of small intrahepatic bile ducts
- "Florid duct lesion" — Granulomatous inflammation around bile ducts
- Progressive ductopenia (loss of bile ducts)
- Cholestasis → Fibrosis → Cirrhosis
Pathology
- Granulomatous cholangitis
- Portal inflammation
- Progressive fibrosis
Consequences of Cholestasis
- Fat malabsorption (fat-soluble vitamin deficiency: A, D, E, K)
- Hypercholesterolaemia (xanthelasma)
- Osteoporosis (reduced vitamin D)
Symptoms
| Feature | Notes |
|---|---|
| Asymptomatic | 50% at diagnosis (detected by raised ALP) |
| Pruritus | Severe, often debilitating; Worse at night |
| Fatigue | Common, not correlated with disease stage |
| Xanthelasma | Yellow plaques around eyes |
| Jaundice | Late sign (indicates advanced disease) |
Examination Findings
Inspection
- Xanthelasma
- Jaundice (late)
- Excoriations (from scratching)
- Hyperpigmentation
Palpation
- Hepatomegaly (smooth, firm)
- Splenomegaly (if cirrhosis)
Signs of Cirrhosis (Late)
- Ascites
- Spider naevi
- Palmar erythema
- Gynecomastia
Blood Tests
| Test | Findings |
|---|---|
| ALP | Raised (cholestatic pattern) |
| GGT | Raised |
| Bilirubin | Normal early; Raised late (poor prognostic marker) |
| AST/ALT | Mildly raised |
| IgM | Raised |
| Cholesterol | Raised |
Immunology
| Test | Findings |
|---|---|
| AMA | Positive in >5% (M2 subtype most specific) |
| ANA | Positive in 30-50% (AMA-negative PBC) |
Imaging
- USS liver: Exclude biliary obstruction
- Fibroscan: Assess fibrosis
Liver Biopsy
- Not always required for diagnosis (AMA + cholestatic LFTs often sufficient)
- Shows florid duct lesion, granulomatous cholangitis
Management Approach
┌──────────────────────────────────────────────────────────┐
│ PRIMARY BILIARY CHOLANGITIS MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ FIRST-LINE: URSODEOXYCHOLIC ACID (UDCA) │
│ • Dose: 13-15 mg/kg/day │
│ • Improves cholestasis │
│ • Slows disease progression │
│ • Improves transplant-free survival │
│ • ~60-70% respond adequately │
│ │
│ SECOND-LINE (UDCA NON-RESPONDERS): │
│ • Obeticholic Acid (FXR agonist) │
│ • Fibrates (off-label, Bezafibrate) │
│ │
│ PRURITUS MANAGEMENT: │
│ • Cholestyramine (bile acid sequestrant) — First-line │
│ • Rifampicin — Second-line (monitor LFTs) │
│ • Naltrexone — Third-line │
│ • Sertraline — Adjunct │
│ │
│ FAT-SOLUBLE VITAMINS: │
│ • Replace Vitamins A, D, E, K │
│ • Calcium and Vitamin D for osteoporosis │
│ │
│ MONITORING: │
│ • LFTs every 6-12 months │
│ • Fibroscan for fibrosis progression │
│ • USS ± AFP (HCC surveillance if cirrhotic) │
│ │
│ LIVER TRANSPLANTATION: │
│ • For decompensated cirrhosis │
│ • For intractable pruritus │
│ • Excellent outcomes; Recurrence ~20% in graft │
│ │
└──────────────────────────────────────────────────────────┘
Of PBC
- Cirrhosis and portal hypertension
- Hepatocellular carcinoma (HCC)
- Varices and variceal bleeding
- Ascites
- Osteoporosis
- Fat-soluble vitamin deficiency
Of Treatment
- UDCA: Generally well-tolerated; Diarrhoea
- Obeticholic acid: Pruritus (paradoxically)
- Cholestyramine: Constipation, Malabsorption
With UDCA Treatment
- Transplant-free survival approaches normal if good biochemical response
Without Treatment
- Median survival 10-15 years from diagnosis
- Progression to cirrhosis
Risk Stratification
- Bilirubin and albumin are key prognostic markers
Key Guidelines
- EASL: Clinical Practice Guidelines on Primary Biliary Cholangitis
- BSG: UK-PBC Guidelines
Key Evidence
UDCA
- RCT evidence for improved survival
Obeticholic Acid
- POISE trial: Improved biochemical markers
What is PBC?
Primary Biliary Cholangitis (PBC) is a condition where the body's immune system attacks the small tubes (bile ducts) inside the liver. This causes damage and eventually scarring.
Who Gets It?
It mainly affects women aged 40-60. The cause is unknown, but it's linked to the immune system.
What Are the Symptoms?
- Itching (can be severe)
- Tiredness
- Yellow fatty lumps around the eyes (xanthelasma)
- Jaundice (yellow skin and eyes) — a late sign
How is It Diagnosed?
A blood test shows:
- A specific antibody called AMA (Anti-Mitochondrial Antibody)
- Raised liver enzymes (especially ALP)
How is It Treated?
- A medication called Ursodeoxycholic Acid (UDCA) helps protect the liver and slow the disease
- Medications to help with itching
- If the liver fails, a liver transplant can cure the disease
What's the Outlook?
Most people with PBC live a normal life if treated early. Regular check-ups are important.
Primary Guidelines
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145-172. PMID: 28427765
Key Studies
- Nevens F, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis (POISE). N Engl J Med. 2016;375(7):631-643. PMID: 27532830