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

XII. Resources

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

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Related Studies

Ontology: Primary biliary cirrhosis (C0008312)

Definition (NCI) An autoimmune inflammatory disorder characterized by destruction of the small intrahepatic bile ducts. It affects predominantly females and it may lead to cirrhosis and liver failure. Patients have antimitochondrial and antinuclear antibodies in the peripheral blood.
Definition (CSP) a form of biliary cirrhosis in which small intrahepatic ducts are destroyed while the major intra and extra hepatic ducts remain patent; most patients are middle aged females and have circulating antimitochondrial antibodies.
Concepts Disease or Syndrome (T047)
MSH D008105
ICD10 K74.3
SnomedCT 155815006, 266540000, 1761006, 31712002
English Chronic non-suppurative destructive cholangitis, Cholangitis, Chronic Nonsuppurative Destructive, BILIARY CIRRHOSIS PRIMARY, primary biliary cirrhosis (diagnosis), primary biliary cirrhosis, Biliary cirrhosis primary, PBC1, PBC, BILIARY CIRRHOSIS, PRIMARY, 1, Primary Bilary Cirrhosis (PBC), biliary cirrhosis primary, biliary cirrhosis pbc primary, cirrhosis primary biliary, pbc, Biliary Cirrhosis, Primary, 1, Biliary cirrhosis (& [primary]) (disorder), Biliary cirrhosis, Biliary cirrhosis (& [primary]), Primary Biliary Cirrhosis, Chronic nonsuppurative destructive cholangitis, PBC- Primary biliary cirrhosis, Primary biliary cirrhosis (disorder), Primary biliary cirrhosis, biliary; cirrhosis, primary, Hanot, cholangitis; chronic nonsuppurative destructive, chronic; cholangitis, chronic nonsuppurative destructive, destructive, cirrhosis; biliary, primary, Chronic Non-Suppurative Destructive Cholangitis, Biliary Cirrhosis, Primary, Cirrhosis;biliary;primary
Dutch primaire biliaire cirrose, chronische niet-etterende destructieve cholangitis, biliair; cirrose, primair, cholangitis; chronisch niet-suppuratief destructief, chronisch; cholangitis, niet-suppuratief, destructief, cirrose; biliair, primair, Primaire biliaire cirrose, galblaascirrose primair, Cholangitis, chronische non-suppuratieve, Biliaire cirrose, primaire
French CBP, Cholangite destructrice non suppurée chronique, Cirrhose biliaire primitive, Cholangite destructrice chronique non suppurative, Cholangite destructive chronique non suppurative, Cirrhose biliaire primaire, Maladie de Hanot, Syndrome de Hanot
German primaere biliaere Zirrhose, PBC, chronische nicht-eitrige destruktive Cholangitis, Cholangitis, chronische nichteitrige destruktive, Primaere biliaere Zirrhose, biliaere Zirrhose primaer
Italian Colangite destruente cronica non suppurativa, Colangite distruttiva cronica non suppurativa, Cirrosi biliare primitiva, Cirrosi biliare primaria
Portuguese Colangite destrutiva não purulenta crónica, Cirrose Biliar Primária, Cirrose biliar primária, Colangite Crônica Destrutiva não Supurativa
Spanish CBP, Colangitis destructiva no supurativa crónica, Cirrosis Biliar Primaria, cirrosis biliar primaria (trastorno), cirrosis biliar primaria, colangitis crónica destructiva no supurativa, Cirrosis biliar primaria, Colangitis Crónica Destructiva no Supurativa
Japanese 原発性胆汁性肝硬変, 慢性非化膿性破壊性胆管炎, ゲンパツセイタンジュウセイカンコウヘン, マンセイヒカノウセイハカイセイタンカンエン
Czech Primární biliární cirhóza, Chronická nehnisavá destruktivní cholangitida, primární biliární cirhóza
Korean 원발성 담즙성 경화
Hungarian PBC, Chronicus nem-suppurativ destructiv cholangitis, Primaer biliaris cirrhosis, Primer biliaris cirrhosis
Norwegian Kronisk ikke-purulent destruktiv kolangitt, Primær biliær cirrhose, Biliær cirrhose, primær