Primary Biliary Cirrhosis

Aka: Primary Biliary Cirrhosis, Primary Biliary Cholangitis

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II. Epidemiology

  1. Gender: Primarily female (90%)
  2. Age: Middle age (median 50 years old)
  3. Prevalence varies by geographic region
    1. United States: 400 per million
    2. Europe: 200 to 250 per million
    3. Africa and Asia: 20 per million (may represent under-detection)
  4. Genetic factors
    1. Concordance rate 63% among monozygotic twins, and 4% among first degree relatives

III. Pathophysiology

  1. Autoimmune inflammatory condition resulting in destruction of small intrahepatic bile ducts
  2. Large intra- and extrahepatic ducts are preserved
  3. Results in slowly progressive cholestatic liver disease
  4. Environmental exposures likely play a role but are not specifically identified
    1. Various infectious agents (including Recurrent UTI - see below)

IV. Findings

  1. Fatigue (>20% of patients)
  2. Pruritus (>20% of patients)
  3. Jaundice (>10% of patients)
  4. Xanthomas (>15% of patients)

V. Associated Conditions

  1. Recurrent Urinary Tract Infections (esp. E. coli)
  2. Autoimmune disorders
    1. Celiac Sprue
    2. Autoimmune Thyroid disorders

VI. Labs

  1. Liver Function Test abnormalities
    1. Direct Bilirubin (Conjugated Bilirubin) increased
    2. Alkaline Phosphatase increased
    3. Serum transaminases increased
  2. Rheumatologic lab abnormalities
    1. Anti-mitochondrial Antibody positive (>1:40 titer in 90% of patients)
  3. Other non-specific findings
    1. Hypercholesterolemia

VII. Differential Diagnosis

  1. See Serum Alkaline Phosphatase for other causes of increased levels
  2. See Liver Function Test anormality
  3. See Drug Induced Liver Injury

VIII. Diagnosis

  1. Primary Biliary Cirrhosis (PBC)
    1. Anti-mitochondrial Antibody positive (>1:40 titer) AND
    2. Alkaline Phosphatase >1.5x normal for >24 weeks (5.5 months) AND
    3. Liver biopsy positive
      1. Nonsuppurative destructive Cholangitis
      2. Interlobular bile duct destruction
  2. Variants (5-10% of cases)
    1. Autoimmune Hepatitis (AIH) Overlap with Primary Biliary Cirrhosis (PBC)
      1. PBC precedes AIH by 6 years
      2. Serum Alanine Aminotransferase >=5x upper limit of normal
      3. Serum IgG levels >2 fold above the upper limit of normal
      4. Positive anti-Smooth Muscle Antibody (Anti-SmA)
      5. Liver biopsy with moderate to severe perioportal or periseptal necrosis (lymphocytic)
    2. Primary Biliary Cirrhosis with negative AMA (Antimitochondrial Antibody)
      1. Diagnosis is identified on liver biopsy
      2. Recheck AMA with serial repeat testing, sensitive assays, and 3 mitochondrial autoantigens
      3. Consider alternative causes for Cholangitis

IX. Management

  1. Ursodeoxycholic Acid (UDCA)
    1. Primary medication to reduce bile acid concentrations
    2. Dose: 13 to 15 mg/kg/day
  2. Corticosteroids
    1. Used in Autoimmune Hepatitis (AIH) Overlap with Primary Biliary Cirrhosis (PBC)
    2. Adjunct to Ursodeoxycholic Acid
  3. Pruritus Management
    1. Cholestyramine
    2. Dermatology Consultation
    3. Consider Sertraline, Rifaximin or Rifampin, or Naltrexone
    4. Antihistamines (e.g. Diphenhydramine, Hydroxyzine)
  4. Osteopenia or Osteoporosis Management
    1. Obtain DEXA Scan at time of Primary Biliary Cirrhosis diagnosis
    2. Alendronate
    3. Calcium Supplementation
    4. Vitamin D Supplementation
  5. Sjogren's Syndrome
    1. See Xerostomia of oral care recommendations
    2. Artificial tears
    3. Saliva Substitute
    4. Cyclosporine Ophthalmic Emulsion
  6. Hyperlipidemia
    1. Statins are typically considered safe and effective in Primary Biliary Cirrhosis
  7. Steatorrhea
    1. Evaluate for underlying cause
    2. If small intestinal Bacterial overgrowth
      1. Consider intermittent broad spectrum Antibiotics
    3. If Inadequate bile acids in the Small Intestine
      1. Decrease total fat intake
      2. Prefer medium chain Triglycerides over long chain Triglycerides
  8. Liver Transplantation
    1. Indicated in advanced Primary Biliary Cirrhosis

X. Complications

  1. Cirrhosis, hepatic failure and related complications (e.g. Esophageal Varices, Ascites, Hepatorenal Syndrome)
  2. Autoimmune Chronic Pancreatitis
  3. Hypercholesterolemia and Dyslipidemia (>75% of patients)
  4. Osteoporosis (35% of patients)
  5. Fat Soluble Vitamin Deficiency (Vitamins A, D, E, and K due to malabsorption)
  6. Globus pallidum manganese deposition
    1. One of the proposed causes of Fatigue in Primary Biliary Cirrhosis

XI. Prognosis

  1. Mayo Risk Score
    1. https://www.mayoclinic.org/medical-professionals/transplant-medicine/calculators/the-updated-natural-history-model-for-primary-biliary-cholangitis/itt-20434724
    2. Predicts 2 year survival
    3. Mayo Risk Score >=7.8 identifies patients at optimal stage for Liver Transplant

XII. Resources

  1. Primary Biliary Cirrhosis (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK459209/

XIII. References

  1. Purohit (2015) World J Hepatol 7(7):926-41 +PMID: 25954476 [PubMed]

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