What does PBC (Primary Biliary Cholangitis) stand for and what is its treatment?

Primary Biliary Cholangitis (PBC): Definition and Treatment

PBC stands for Primary Biliary Cholangitis (formerly known as Primary Biliary Cirrhosis), a chronic autoimmune liver disease characterized by progressive destruction of small intrahepatic bile ducts that can lead to cirrhosis and liver failure if untreated 1.

Disease Overview

PBC is a cholestatic autoimmune disorder that predominantly affects middle-aged women (fourth to seventh decades of life), though contemporary data show higher prevalence in males and racial minorities than historically recognized 1, 2. The disease is marked by:

• Chronic destructive inflammation of interlobular bile ducts 1
• Presence of antimitochondrial antibodies (AMA) in approximately 95% of cases 1
• Cholestatic liver biochemistry with parallel increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) 3

Treatment Approach

First-Line Therapy

Ursodeoxycholic acid (UDCA) at 13-15 mg/kg daily is the foundational treatment for all patients with PBC and has dramatically improved disease prognosis 1, 3. UDCA delays disease progression in most patients, though it has no impact on PBC symptoms 4.

• Treatment goal: Maximize reduction in serum alkaline phosphatase levels 4
• Response rate: 60-70% of patients achieve adequate biochemical response 3, 4
• Non-responders: 30-40% have inadequate response and remain at high risk for complications, requiring second-line therapy 3

Second-Line Therapies

For patients with inadequate response to UDCA or UDCA intolerance, several options are now available:

Obeticholic Acid (OCA)

• FDA-approved for PBC patients without cirrhosis or with compensated cirrhosis without portal hypertension, either combined with UDCA or as monotherapy 5
• Dosing consideration: Requires careful patient selection due to contraindications in decompensated cirrhosis 5
• Major limitation: High propensity to induce or worsen pruritus 4
• Benefit: Significantly improves liver biochemistries and associated with improved long-term clinical outcomes 4

PPAR Agonists (Recently Approved)

• Elafibranor and seladelpar: Recently approved peroxisome proliferator-activated receptor (PPAR) agonists 6, 4
• Advantage over OCA: May actually improve pruritus symptoms rather than worsen them 4
• Efficacy: Show biochemical improvements in UDCA inadequate responders 4

Off-Label Fibrates

• Bezafibrate and fenofibrate: Available as off-label second-line therapies 4, 2
• Use pattern: Should be considered in association with UDCA for inadequate responders 3

Liver Transplantation

Liver transplantation is the only effective treatment for liver failure secondary to PBC 1. Key considerations:

• Excellent outcomes: 70% of patients survive at least 10 years post-transplant, with 1-year survival >90% and 3-year survival ~85% 1
• Survival benefit: Evident as early as 3 months post-surgery, with 2-year survival more than twice that predicted for conservative treatment 1
• Rare indication: Occasionally required for severe, intractable pruritus with sleep deprivation and emotional disturbance, though all medical options should be exhausted first 1
• Timing: Consider when UKELD score >49, jaundice, portal hypertension, or early decompensation signs appear 1

Symptom Management

Fatigue is the symptom with the biggest impact on quality of life in PBC patients 1. Management includes:

• Patient support groups: Strongly recommended for all PBC patients 1
• Psychological services: Refer patients with profound psychological distress associated with fatigue for assessment 1
• Exercise therapy: Pilot trial evidence suggests benefit for fatigue, though patients often lack confidence to exercise 1

Monitoring and Complications

Regular surveillance is essential for patients with advanced disease:

• Hepatocellular carcinoma (HCC) screening: Required in cirrhotic patients, with increased risk in UDCA non-responders and male patients 1
• Variceal screening: Follow BSG guidelines for patients with suspected portal hypertension 1
• Liver function monitoring: Periodic laboratory testing required during OCALIVA treatment to assess for hepatic decompensation 5

Common Pitfalls to Avoid

• Do not use obeticholic acid in patients with decompensated cirrhosis or complete bile duct obstruction—this is contraindicated and can cause hepatic decompensation and failure 5
• Do not assume cardiac risk is increased in PBC despite cholesterol elevations; patients have normal cardiac risk but require appropriate preventative screening 1
• Do not screen daughters routinely for PBC; lifetime risk is <1% despite slightly increased familial risk 1
• Do not advise complete alcohol abstinence in early-stage disease; patients can drink within safe limits, though those with advanced disease should abstain 1