College Answer

(c)       Over the next 48 hours he develops increasing jaundice, with severe derangement of his Liver Function  Tests. What are the likely causes, and how are you going to manage this problem?

The potential causes of jaundice and abnormal LFTs within the first 72 hours are many. The pattern of elevation may help the diagnosis (eg. hepatocellular pattern [elevated transaminases, but minor elevation of Alkaline Phosphatase], cholestatic [minor elevation of transaminases]), and a systematic approach is helpful. Most likely causes include infection (systemic sepsis, mild hepatitic/intravascular cholestasis, liver abscess, acalculous cholecystitis), drug induced (cholestatic/hepatitic), haemodynamic/shock (ischaemic hepatitis) or haemolysis (sepsis, early destruction of transfused blood). Pre-existing intercurrent diseases (hepatitis, gall stones) could also be present.

Management depends on the specific/likely aetiology. A careful history (including drug history [eg. high dose of paracetamol before presentation]) and clinical examination (eg. signs of right heart failure, chronic liver disease, abdominal pain) followed by specific liver function tests to delineate the pattern of abnormality (including alkaline phosphatase [AP], gamma glutamyl transpeptidase [GGT] and/or conjugated/unconjugated bilirubin). More specific blood tests may be indicated (eg. haemolysis screen or viral serology). Imaging of right upper quadrant with ultrasound (to assess obstruction &/or stones) would usually be indicated (± other imaging eg. nuclear medicine or CT scan). After addressing the specific aetiology, further treatment would be largely supportive (with awareness of effects on drug metabolism).

Discussion

 The college has cheated the candidate by not presenting them with a list of LFTs to analyse. With no information, the differentials (and thus the manaement options) are distrubingly broad.

One can work though this systematically.

The following tests will need to be ordered, in order of escalating expense, invasiveness and esotericims:

• Albumin is a test of synthetic liver function, but is very nonspecific in critical illness.
• Coags: APTT, PT, fibrinogen and mixing studies. These test the synthetic liver function. PT will be raised if the liver has stopped storing fat-soluble vitamins, and APTT will be raised if the synthetic function is so poor that clotting factor synthesis is impaired. Mixing studies help to demonstrate that the addition of healthy plasma corrects the factor deficiency.
• Bilirubin differential (conjgated vs. unconjugated) helps discriminate biliary from nonbiliary causes of jaundice
• Amylase and lipase (to exclude pancreatitis)
• Ultrasound of the liver and biliary tree to rule out bile duct obstruction and any interruption of the hepatic vascular supply; and to look at the hepatic parenchymal texture (eg. fatty, cirrhotic, etc)
• Hepatitis virus tests  to rule out acute hepatitis
• Iron studies (to look for haemochromatosis)
• Ceruloplasmin (if Wilson's disease is a realistic possibility)
• Anti-smooth muscle antibodies (primary sclerosing cholangitis)
• Anti-liver microsomal antibodies (autoimmune hepatitis)
• Serum α-1 antitrypsin level (for deficiency)
• Liver biopsy (gold standard)

Differentials and their management

• Poor hepatic blood flow
  • decrease the PEEP to improve viscera
• Right heart failure
  • maintain cardiac output with inotropes and fluids
• Generalised shock state
  • maintain normotension with fluids and vasopressors
• Idiopathic drug reaction
  • change the offending drug to an analogue
• Hepatic vein thrombosis
  • anticoagulation
• Hepatic infarction
  • anticoagulation
• Infectious cause
  • viral serology
  • blood cultures

In addition, one would need to adjust drug doses and dosing intervals to allow for changes in hepatic clearance.