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

• 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)
  • 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)

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)