Primary Biliary Cholangitis (PBC)
BSG and UKPBC primary biliary cholangitis treatment and management guidelines
Overview Table
Primary Biliary Cholangitis (PBC) vs Primary Sclerosing Cholangitis (PSC)
Note that PBC and PSC are 2 distinct conditions, but they share several important similarities. It’s therefore essential to be able to differentiate between them:
- Both cause chronic cholestatic liver disease
- Both involve pathological injury to the biliary tree
| Feature | PBC | PSC |
|---|---|---|
| Site of disease | Intrahepatic bile ducts | Intra- AND extrahepatic bile ducts |
| Association | Autoimmune diseases | Ulcerative colitis |
| Antibodies | AMA +ve | p-ANCA positive (non-specific) |
| Diagnosis | Cholestatic LFT + antibodies +/- liver biopsy | MRCP |
| Treatment | Ursodeoxycholic acid | Limited treatment |
| Main complication | Osteoporosis, cirrhosis, hepatocellular carcinoma | Cholangiocarcinoma |
Background Information
Definition
PBC is a chronic, progressive cholestatic liver disease, characterised by autoimmune destruction of the intrahepatic bile ducts
Risk Factors
PBC is associated with both genetic and environmental factors: [Ref]
| Genetic susceptibility |
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| Environmental triggers |
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PBC is often associated with other autoimmune conditions:
- Sjogren’s syndrome (one of the most common autoimmune associations) [Ref]
- Both PBC and Sjogren’s syndrome commonly present with sicca symptoms
- Coeliac disease
- Autoimmune thyroid disease
- Systemic sclerosis or CREST syndrome
- Rheumatoid arthritis
Complications
Key complications: [Ref]
- Dyslipidaemia (esp. hypercholesterolaemia) and metabolic syndrome (up to ~80% patients)
- Interestingly, the dyslipidaemia alone does NOT increase the risk of cardiovascular disease
- Complications from chronic cholestasis
- Fat-soluble vitamin (A D E K) deficiency
- Osteoporosis
- Liver cirrhosis and hepatocellular carcinoma
Diagnosis
A classic mnemonic to remember the key features of PBC is the “Ms”:
- Middle-aged
- Male sparing (i.e. females)
- AIgM +ve
Clinical Features
Most cases occur in middle-aged women (40-70 y/o)
Key presenting features: [Ref1][Ref2]
| Early-stage disease | 50% patients are asymptomatic at diagnosis (often detected by ↑ ALP or during autoimmune screen)
If symptomatic:
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| Late-stage disease |
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In PBC, features of overt cholestasis (e.g. jaundice, pale stools, dark urine) usually occur only in the later stages of disease.
In contrast, pruritus often presents early, as it is mediated by specific cholestatic pruritogens (such as lysophosphatidic acid and autotaxin) rather than by bile acid accumulation alone.
Investigation and Diagnosis
Diagnostic criteria (at least 2 out of 3 of the following components): [Ref]
| Component | Diagnostic criteria | Other typical findings (but not part of the diagnostic criteria) |
|---|---|---|
| Cholestatic LFTs |
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| Characteristic serology |
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| Liver biopsy (definitive test) | Non-suppurative destructive cholangitis affecting small intrahepatic bile ducts (esp. interlobular and septal ducts)
|
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Imaging should be routinely offered
- 1st line: abdominal ultrasound
- However, imaging has no role in helping diagnose PBC (it is often normal in PBC as the pathology is in the intrahepatic ducts)
- Its role is mainly to exclude differential diagnoses or detect cirrhosis
The presence of cholestatic LFTs + characteristic serology is sufficient to diagnose PBC. (Remember the diagnostic criteria are 2 out of 3).
Therefore, liver biopsy is not routinely required to diagnose PBC. But it should be considered when serology is negative, findings are atypical, or coexisting liver pathology (e.g. autoimmune hepatitis overlap).
Exam Tip
If asked for the most appropriate first-line investigation for suspected primary biliary cholangitis, antimitochondrial antibody (AMA) serology should be chosen unless imaging is specifically requested.
AMA is highly sensitive and specific and forms part of the diagnostic criteria, particularly with a cholestatic LFT pattern (raised ALP). Ultrasound is not diagnostic for PBC and is mainly used to exclude other causes of cholestasis, such as biliary obstruction.
Management
Pharmacological Management
Disease-Modifying Therapy
All patients should be started on ursodeoxycholic acid for life (improves transplant-free survival and delays progression to cirrhosis)
2nd line agents (if non-responders to ursodeoxycholic acid)
- Obeticholic acid (semi-bile acid analogue)
Fibrates and budesonide are off-label therapies.
Symptom-Directed Therapy
| Pruritus |
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| Fatigue |
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| Sicca syndrome |
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Liver Transplantation
Liver transplantation is the only curative treatment for PBC. However, most patients do NOT require transplantation due to improved outcomes with ursodeoxycholic acid
Indications to consider liver transplantation:
- Bilirubin > 50µmol/L
- Decompensated liver disease
- Severe, intractable pruritus
Note that recurrence of PBC post-transplant can occur, therefore lifelong monitoring is necessary, even after a transplant
Monitoring
BSG guidelines state that it is reasonable to screen all PBC patients for coeliac disease, thyroid disease, and Sjogren’s syndrome after diagnosis
Lifelong monitoring is necessary for PBC: [Ref]
- LFTs every 3-6 months (to monitor disease progression)
- Bone mineral density measurement (DEXA) every 2 years
- Vitamins A, D, E and prothrombin time annually if bilirubin >2.0
- If the patient develops cirrhosis, screen for complications accordingly
- Ultrasound +/- AFP every 6 months (for HCC)
- Upper GI endoscopy at baseline (for oesophageal varices)
- See the Cirrhosis article for more details