Primary Biliary Cholangitis

Snapshot

A 40-year-old woman presents to the urgent care for excessive fatigue and jaundice. She reports that she had felt fatigued for months. Recently, she noticed that her skin is more orange. On physical exam, she is noted to have scleral icterus and jaundice. Laboratory results reveal transaminitis. Anti-smooth muscle antibodies were negative, but a liver biopsy showed granulomatous inflammation of the bile ducts.

Introduction

Overview
- primary biliary cholangitis (PBC) is a granulomatous autoimmune condition resulting in destruction of the interlobular bile ducts
  - also known as primary biliary cirrhosis
Epidemiology
- demographics
  - female > male
  - middle-aged (>40 years of age)
- risk factors
  - family history
Pathogenesis
- autoimmune attack on anti-mitochondrial antigens on biliary epithelial cells
- autoantibodies
  - anti-mitochondrial antibodies (AMAs)
Associated conditions
- other autoimmune diseases
  - CREST syndrome
  - rheumatoid arthritis
  - celiac disease
  - Hashimoto thyroiditis
scleroderma

Presentation

Imaging

Ultrasound
- indication
  - to assess for hepatobiliary disease
- views
  - right upper quadrant
- findings
  - cirrhosis, including increased nodularity, atrophy, or hypertrophy
  - distinguish between intra and extrahepatic biliary obstruction
ERCP (endoscopic retrograde cholangiopancreatography)
- indication
  - ultrasound is inconclusive, or concern for gallstones
- findings
  - extrahepatic ducts appear grossly normal
contrast to “string of beads” in primary sclerosing cholangitis

Studies

Serum labs
- liver function tests showing cholestasis pattern
  - ↑ direct bilirubin
  - ↑ alkaline phosphatase
- autoantibodies
  - + anti-mitochondrial antibody (AMA)
    - 90-95% sensitivity
    - > 99% specificity
  - + anti-smooth muscle antibody (ASMA)
    - in 50% of patients
  - + anti-nuclear antibody (ANA)
    - in 50% of patients
- ↑ IgM
- ↑ cholesterol
Invasive studies
- liver biopsy
  - indication
    - in AMA-negative patients in whom clinical suspicion is strong for PBC
  - findings
    - nonsuppurative cholangitis and destruction of interlobular biliary ducts
    - degenerating bile duct with lymphoid structures and granulomas
Diagnosis with 2 or more of
- alkaline phosphatase > 1.5x upper limit of normal for 6 months or more
- + AMA in serum
liver biopsy showing signs of PBC

Differential

Hemochromatosis
- key distinguishing factor
  - triad of cirrhosis, diabetes, and skin bronze pigmentation
Wilson disease
- key distinguishing factors
  - patients typically present before age 40
cirrhosis, neurologic disease, psychiatric disease, and Kayser-Fleischer rings in the eyes

Treatment

Lifestyle
- avoidance of alcohol
- vaccination against hepatitis A and B
Medical
- ursodeoxycholic acid
  - indications
    - all patients
- cholestyramine
  - indications
    - pruritus
Surgical
- liver transplantation
  - indications
    - decompensated liver disease
severe pruritus refractory to other therapies

Complications