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)
- Synthetic parameters: Do not (generally) point to a specific etiology of liver disease, but rather, indicate severity of disease involving the liver
Principles of Management
- 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
- Ursodiol 13-15 mg/kk/day-improves biochemical indices but unclear benefit with respect to clinical outcomes
- Treat Symptoms
- Pruritus
- Cholestyramine 4 g PO up to QID
- Major SE: Poor taste and GI upset
- Antihistamines do not usually confer relief
- Other: Rifampin, Naltrexone, Sertraline
- Cholestyramine 4 g PO up to QID
- Pruritus
- Screen for and treat complications
- Psychosocial
- Malabsorption (of fat soluable vitamins)
- Vitamin A (night blindness)-do not empirically replace until level is checked because hypervitaminosis A is associated with hepatotoxicity
- if checking level, check Zn level also as may need to replace both
- Vitamin D (osteopenia/bone disease)-calcium, vitamin D, alendronate
- Vitamin K (coagulopathy)-replacement (route depends on urgency)
- Vitamin A (night blindness)-do not empirically replace until level is checked because hypervitaminosis A is associated with hepatotoxicity
- 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
- Avoid drugs that promote cholestasis and may worsen pruritus (i.e. estrogens)