What is Primary Biliary Cholangitis (PBC)?

Primary Biliary Cholangitis (PBC): A Comprehensive Overview

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of small bile ducts, leading to cholestasis, fibrosis, and potentially cirrhosis if left untreated. 1

Definition and Pathophysiology

PBC is an immune-mediated liver disease where patients develop a well-orchestrated immune reaction against mitochondrial antigens that specifically targets intrahepatic biliary cells. The disease results from a combination of genetic and environmental risk factors, with a strong female predominance. Key features include:

• Destructive, small duct lymphocytic cholangitis
• Presence of antimitochondrial antibodies (AMA) in 90-95% of patients
• Progressive cholestasis that can lead to cirrhosis if untreated

Epidemiology

• More common in women than men
• Peak incidence around middle age
• Family members of patients with PBC have a 10.5-fold higher risk of developing the disease
• Daughters of patients have a 35-fold increased risk compared to the general population 1
• The lifetime risk for daughters of PBC patients developing the disease is less than 1% 1

Clinical Presentation

PBC can present with various symptoms, though many patients are asymptomatic at diagnosis:

• Fatigue (the symptom with biggest impact on quality of life) 1
• Pruritus (itching)
• Right upper quadrant discomfort
• Jaundice (in advanced disease)
• Xanthomas and xanthelasma (in advanced disease with hypercholesterolemia)

Diagnosis

Diagnosis is typically based on:

1. Biochemical evidence of cholestasis: Elevated alkaline phosphatase (ALP)
2. Serological testing: Presence of antimitochondrial antibodies (AMA)
3. Exclusion of other causes of liver disease

Liver biopsy is not required for diagnosis in most cases but may be helpful in:

• AMA-negative cases
• Suspected overlap with autoimmune hepatitis
• Excluding other liver diseases

Variant Presentations

AMA-Negative PBC

• Approximately 5% of PBC patients are AMA-negative
• Most will be positive for PBC-specific nuclear antibodies
• Management is the same as for AMA-positive disease 1

AMA-Positive with Normal Liver Tests

• Up to 0.5% of the population may be AMA-positive with normal liver biochemistry
• These individuals should be screened yearly for biochemical abnormalities
• Follow-up can occur in primary care unless there are specific factors warranting specialist care 1

PBC/AIH Overlap Syndrome

• True overlap with autoimmune hepatitis is rare
• When suspected, liver biopsy with expert clinicopathological review is needed to guide treatment 1
• Biochemical evidence of marked hepatitic activity (transaminases >5× ULN) and elevated IgG concentrations should prompt consideration of liver biopsy 1

Treatment

First-Line Therapy

• Ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day is the standard first-line treatment
• UDCA is considered safe during conception, pregnancy, and post-partum 1

Second-Line Therapy

• For patients with inadequate response to UDCA after 1 year:
  • Obeticholic acid (FDA-approved) 2
  • Fibrates (off-label use)

Management of Symptoms

For pruritus:

• Cholestyramine (first-line)
• Rifampicin (second-line)
• Other options: naltrexone, sertraline
• In pregnancy, both cholestyramine and rifampicin (second trimester onwards) are considered safe 1

For fatigue:

• Address contributing factors (anemia, hypothyroidism, sleep disturbance)
• Psychological approaches such as cognitive behavioral therapy may help 1

Monitoring and Follow-up

Regular monitoring is essential to:

• Assess response to therapy
• Detect disease progression
• Screen for complications

Special Considerations

Pregnancy and PBC

• Pregnancy is typically well-tolerated in non-cirrhotic patients
• Pruritus may worsen during pregnancy
• UDCA should be continued during conception, pregnancy, and post-partum 1
• Pregnant patients should be screened for anti-Ro and anti-La antibodies 1

Lifestyle Considerations

• Diet: Most patients can eat a normal healthy diet; those with cholestasis may need monitoring for fat-soluble vitamin deficiencies 1
• Alcohol: No evidence that moderate alcohol consumption worsens PBC, though patients with advanced liver disease should abstain 1
• Smoking: Patients should avoid smoking as it may be associated with more aggressive disease 1

Complications

• Progressive liver fibrosis leading to cirrhosis
• Portal hypertension
• Hepatocellular carcinoma (in patients with advanced disease) 1
• Metabolic bone disease

Patient Support

Patients with PBC should be offered the chance to seek support from patient support groups, as fatigue can lead to social isolation and reduced quality of life 1. Several organizations provide support:

• The PBC Foundation
• The British Liver Trust
• LIVErNorth
• Liver4Life

Common Questions and Pitfalls

• Is PBC inherited? While there is an increased risk in family members, PBC does not follow Mendelian inheritance patterns 1
• Is cardiac risk increased? No robust evidence suggests increased atherosclerotic risk despite cholesterol elevations 1
• Is PBC transmissible? No, there is no evidence of disease transmission 1
• Cancer risk? The only malignancy associated with PBC is hepatocellular carcinoma in patients with advanced disease 1

Conclusion

Early diagnosis and prompt treatment of PBC are essential to prevent disease progression. The management approach should be structured, lifelong, and tailored to the individual patient's presentation and response to therapy.