What is the management approach for a middle-aged woman with Primary Biliary Cholangitis (PBC)?

Management of Primary Biliary Cholangitis

All patients with PBC should be started on ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day as first-line therapy, with biochemical response assessed at 12 months using validated risk scores to determine if second-line agents are needed. 1, 2

Initial Assessment and Baseline Workup

Before initiating treatment, complete the following baseline evaluations:

• Abdominal ultrasound to exclude alternative causes of cholestasis and assess for focal liver lesions 1
• Cirrhosis status determination through clinical assessment, imaging, and laboratory markers to identify contraindications to second-line agents 1
• Osteoporosis risk assessment using DEXA scan or FRAX score, as PBC significantly increases fracture risk 1
• Symptom documentation using validated scales for fatigue and pruritus severity 1

First-Line Treatment: UDCA

Initiate UDCA at 13-15 mg/kg/day (can be taken once daily or divided into 2-3 doses) in all patients without decompensated cirrhosis 1, 2. UDCA significantly decreases serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM levels 1. Long-term treatment delays histological progression when started early and reduces the likelihood of liver transplantation or death in patients with moderate to severe disease 1, 2.

Critical dosing caveat: Never exceed 20 mg/kg/day, as high doses are associated with adverse outcomes in cholestatic liver diseases 2.

Response Assessment at 12 Months

After 1 year of UDCA therapy, perform biochemical response assessment using the GLOBE Score or UK-PBC Risk Score, which are the most accurate predictive models for long-term outcomes 1, 2. This assessment determines whether second-line therapy is needed.

Second-Line Therapy for Inadequate UDCA Response

When patients fail to achieve adequate biochemical response at 12 months, consider adding second-line agents:

Obeticholic Acid (OCA)

• FDA-approved second-line agent that significantly improves liver biochemistries and has been associated with improved long-term clinical outcomes 3
• Major limitation: High propensity to induce severe pruritus (23% in clinical trials) 4
• Absolute contraindications per FDA label: 4
  • Decompensated cirrhosis (Child-Pugh B or C)
  • Compensated cirrhosis with evidence of portal hypertension (ascites, varices, persistent thrombocytopenia)
  • Complete biliary obstruction
• Monitoring requirement: Closely monitor patients with compensated cirrhosis for new evidence of portal hypertension or increases in bilirubin/prothrombin time; permanently discontinue if these develop 4

Peroxisome Proliferator-Activated Receptor (PPAR) Agonists

• Elafibranor and seladelpar are recently FDA-approved agents showing biochemical improvements and may actually improve pruritus symptoms (unlike OCA) 3, 5
• Bezafibrate and fenofibrate are available as off-label third-line options with demonstrated efficacy in prospective multicenter studies 2, 3

Clinical decision-making: Choose OCA when pruritus is absent or mild; choose PPAR agonists (elafibranor, seladelpar, or fibrates) when pruritus is already problematic or when OCA is contraindicated 3.

Symptom Management

Pruritus

UDCA does not improve pruritus 1, 2. For severe pruritus, use a stepwise approach:

1. First-line: Sertraline (SSRI) 1, 2
2. Second-line: Rifampicin (avoid in first trimester of pregnancy) 1, 2
3. Additional options: Bile acid sequestrants (cholestyramine), opioid antagonists (naltrexone, nalmefene) 1, 2

Important timing consideration: If using bile acid sequestrants, administer UDCA at least 4 hours before or after the sequestrant to avoid binding 4.

Fatigue

No consistently effective treatment exists for fatigue in PBC 2. Patients with profound psychological distress associated with fatigue should be referred to appropriate psychological services for assessment, as cognitive behavioral therapy may help manage distress 6.

Ongoing Monitoring During Treatment

• Liver biochemistry regularly to assess treatment response 1, 2
• Annual symptom evaluation for fatigue and pruritus using validated scales 1, 2
• Osteoporosis screening within 5 years in 80% of patients 2
• Hepatocellular carcinoma (HCC) surveillance in patients with advanced disease, particularly UDCA non-responders and male patients 6

Special Populations

Pregnancy

• Pregnancy is typically well tolerated in non-cirrhotic patients, but pruritus can be exacerbated 6
• Continue UDCA throughout pregnancy (peri-conception, peri-partum, and post-partum) at standard doses, as expert practice considers it safe despite limited data 6
• For severe intractable pruritus during pregnancy: Cholestyramine and rifampicin (second trimester onwards) are considered safe; plasmapheresis may help in extreme cases 6
• Screen for anti-Ro and anti-La antibodies in pregnant patients, as their presence requires fetal screening for bradycardia 6
• Patients with portal hypertension should undergo elective endoscopy in the second trimester for variceal screening and management 6
• Monitor closely post-partum as cholestatic flares have been described 6

Advanced Liver Disease

Patients with advanced liver disease should abstain from alcohol completely 6.

Transplant Referral Criteria

Refer to transplant hepatology if: 1

• Bilirubin >50 μmol/L
• Any evidence of decompensated liver disease (ascites, variceal bleeding, hepatic encephalopathy)

Post-Transplant Management

Administer UDCA lifelong at 10-15 mg/kg/day after liver transplantation to prevent disease recurrence 1, 2. Post-transplant UDCA reduces the risk of PBC recurrence and improves graft survival and long-term overall survival 1, 2.

Patient Support and Education

Offer all patients the opportunity to seek support from patient support groups, as this improves quality of life and reduces social isolation 6. Fatigue has the biggest impact on quality of life, and fatigued patients are more vulnerable to emotional distress 6.

Common Pitfalls to Avoid

• Do not screen relatives routinely for PBC, as the lifetime risk for daughters is <1% and screening may cause insurance difficulties 6
• No specific drugs are contraindicated in PBC per se, but always apply caution with any therapeutics as with any liver disease 6
• Cardiac atherosclerotic risk is not increased in PBC despite cholesterol elevations (due to HDL hypercholesterolemia), but maintain normal cardiac preventative screening 6
• PBC is not transmissible to others; reassure patients accordingly 6