I

1
Im sorry but your results are wrong!!!!!

• Dorte Wren, Ian Woodrow, Wilf Blackburn, Steve
  Lee, Ray McMahon, Sandy Smith, Ian Laing

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Patient RC

• 57 year old male
• Ex-smoker
• Retired due to heart problems
• MI 1983 followed by three cardiac arrests
• Hypertension
• Angina
• Treated with Atenolol and GTN spray

• 1999 GP check up
• Diagnosed with Type 2 Diabetes mellitus
• Treated with Gliclazide

3

• Biochemistry
• Ultrasound of liver and spleen
• Enlargement of liver
• Splenomegaly

4

• Further tests (data not available)
• Iron
• Copper
• ?1-antitrypsin
• Hepatitis serology
• Serum electrophoresis

• Preliminary diagnosis
• Chronic liver disease due to alcohol
• Patient denied excessive alcohol intake
• 17/12/2000 Successful hernia operation
• Liver biopsy taken

5

• Liver biopsy 12/2000
• Results
• Established cirrhosis
• Mild degree of steatosis, previous episodes of
  steato-hepatitis
• Active micronodular cirrhosis
• No signs of hepatic failure
• Preliminary diagnosis
• Cirrhotic liver disease query to diabetic fatty
  liver (NASH) or alcohol
• Regular check-ups (next 2 years)
• DM well controlled
• No deterioration in liver function

6

• January 2003 Wigan
• LFTs unchanged (data unavailable)
• Ultrasound liver
• 1cm hypoechoic lesions in right lobe
• CT
• Ill-defined low attenuation areas right lobe
• Query multi-focal hepatoma

7
AFP rising exponentially 01/03
23IU/L 05/03 266IU/L 08/03 2780IU/L UR
GENT ADMISSION TO MRI SEPTEMBER 2003
8

• 2003 MRI
• Lipiodol angiography,
• Liver biopsy of right lobe,
• Staging laparoscopy
• Confirmed micronodular and macronodular cirrhosis
• Dysplasia
• No evidence of hepatocellular carcinoma (HCC)
• AFP
• 03/09/03 8kU/L (0-10kU/L)
• 15/09/03 4kU/L
• 22/09/03 3kU/L
• 29/09/03 2kU/L
• Oct 03 3.9kU/L (WIGAN)

LFTs ALT 39U/L (5-40) AST 45U/L (5-45) ALP
210U/L (70-330) GGT 82U/L (0-65)
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• ?-feto protein (AFP)
• Glycoprotein of foetal origin
• High concentrations in foetus
• Reference range for adults (MRI) 0-10kU/L
• Function unknown, genetically and structurally
• very similar to albumin
• Single polypeptide chain, MM 70kDa
• Half-life 3-5 days

10

• AFP- Tumour marker
• AFP elevated in
• Hepatocellular cancer (HCC),
• Hepatoblastoma
• Germ-cell (nonseminoma) and yolk-sac carcinoma
• 80-85 of patients with PHCC have elevated AFP
• Median level at presentation is 3000kU/L (UK)
• Above 500kU/L indicative of HCC
• Concentration correlates with size of the tumour,
  degree of differentiation
• Monitor treatment
• Prognostic indicator for survival

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AFP in prognosis

• AFP value
• AFP doubling time
• Hepatoma doubling time 6days-6months
• Median doubling time 21 days
• Survival after diagnosis median 3 months

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• AFP increase
• Liver disease - in 95 of patients with
  hepatitis, hepatic necrosis and cirrhosis
• AFP lt200mg/L
• Acute liver failure AFP up to 1000mg/L
• Untreated chronic hepatitis AFP up to 500mg/L
• Acute viral hepatitis B and C AFP up to 100mg/L
• Regeneration
• Extrahepatic biliary obstruction

13

• AFP- measurement
• Two-site fluoroimmunometric assay
• Delfia (MRI)
• Roche system (Wigan)
• Possible analytical explanations
• High dose hook effect
• Autoantibodies against AFP
• Heterophyllic antibodies

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SANDWICH IMMUNOASSAY
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Summary

• Is it assay interference?
• Could not investigate
• Is it PHCC?
• Very doubtful
• Can AFP values increase to this level in the
  context of progressing cirrhosis without PHCC?

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Conclusion

• Even when the tumour markers are very suggestive
  a definitive diagnostic procedure is required for
  proper management.