Primary Biliary Cirrhosis

Case Presentation:

In our morning report at WCH, we discussed a case of a patient referred for evaluation of an asymptomatic, chronic rise in liver indices. Subsequent testing revealed a cholestatic pattern of bloodwork along with a positive anti-mitochondrial antibody, consistent with a diagnosis of primary biliary cirrhosis (PBC).

Learning Points:

1) The prototypical patient features in PBC
2) Syndromes of presentation of PBC
3) Approach to interpretation and evaluation of liver parameters-with emphasis on cholestatic indicators
4) Principles of Management of PBC

The Prototypical Patient:

  • Female>>Male
  • 40-60 years
  • Family History (100x increased in 1st degree relative)
  • Scandanavian
  • Associated conditions:
    • GI: Celiac disease, Autoimmune hepatitis
    • Rheumatologic: Sicca, Sjogrens, Raynaud’s Scleroderma
    • Other: Hypothyroidism, hyperlipidemia

Presenting Complaints

  • Asymptomatic liver abnormality
  • Generalized pruritus
    • precedes jaundice, worst at night
  • Fatigue
  • Jaundice/liver failure (rare)

Approach to Interpretation and Evaluation of Abnormal Liver Indices

Approach to Liver Abnormalities

  • There are 3 principle “sets” of liver bloodwork:
    • Synthetic parameters: Do not (generally) point to a specific etiology of liver disease, but rather, indicate severity of disease involving the liver
      • Investigations: INR, Albumin, Glucose, Platelets
      • Pattern/order of changes may happen in a characteristic pattern as disease progresses (first platelets go down; rise in bilirubin last)Progression of parameters
    • Liver Enzymes: Indicate hepatocyte injury and may help point to an etiology of liver disease
      • Investigations: AST, ALT, LDH
      • Pattern-related diagnostic considerations:
        • DDx for massive AST and/or ALT elevation: Viral hepatitis, drug-induced hepatitis, autoimmune hepatitis, shock liver
        • Ratio of AST and ALT is important; most causes of liver disease ALT>AST
          • EtOH-related liver disease: AST > 2x ALT
    • Markers of Cholestasis: Indicate biliary stasis/obstruction
      • Investigations: ALP, GGT, Bilirubin
      • DDx:
        • Intraluminal obstruction: Stones, strictures, sclerosing cholangitis, helminth
        • Extraluminal obstruction: Pancreatic/other malignancy
        • Intrahepatic ductal: Primary biliary cirrhosis
        • Impaired transport: Drugs (i.e estrogens/OCP)
        • Diffuse liver infiltration (metastases, advanced liver disease of other causes)Differential Diagnosis of cholestasis

Principles of Management

  1. Prevent/stop progression/improve biochemical indices
    • Ursodiol 13-15 mg/kk/day-improves biochemical indices but unclear benefit with respect to clinical outcomes
      • Major SE: diarrhea
  2. Treat Symptoms
    • Pruritus
      • Cholestyramine 4 g PO up to QID
        1. Major SE: Poor taste and GI upset
      • Antihistamines do not usually confer relief
      • Other: Rifampin, Naltrexone, Sertraline
  3. Screen for and treat complications
    • Psychosocial
    • Malabsorption (of fat soluable vitamins)
      1. Vitamin A (night blindness)-do not empirically replace until level is checked because hypervitaminosis A is associated with hepatotoxicity
        1. if checking level, check Zn level also as may need to replace both
      2. Vitamin D (osteopenia/bone disease)-calcium, vitamin D, alendronate
      3. Vitamin K (coagulopathy)-replacement (route depends on urgency)
    • Dyslipidemia-ursodiol may help, next step would be statins
    • Cancer-AFP and Abdo U/S
    • Varices-OGD screening
      • occur earlier than in other causes of liver disease
  4. Avoid drugs that promote cholestasis and may worsen pruritus (i.e. estrogens)

 

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