This presentation is aimed at primary care physicians. It covers the fundamentals of liver function tests, including the basic principles of interpretation, and the key patterns of abnormalities. The focus is on how to approach liver function tests in a primary care setting.

1. Liver Function Tests
An Approach for Primary Care
Dr Jarrod Lee
Consultant Gastroenterologist & Advanced Endoscopist
Mt Elizabeth Novena Hospital
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2. Scope
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Principles of interpreting LFTs
Patterns of abnormal LFTs
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Hepatocellular Damage
Cholestasis
Biosynthetic function
Bilirubin
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3. 'Traditional' Liver Function Test (LFT)
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ALT: alanine transaminase (SGPT)
AST: aspartate transaminase (SGOT)
ALP: alkaline phosphatase
GGT: gamma Glutamyl Transferase
Albumin, bilirubin
Total protein, globulin
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Known as LFT, but they're really not!
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4. Utility of LFTs
• Advantages
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Sensitive, non-invasive method to screen for liver
dysfunction
Patterns of abnormal LFTs can help recognized type of
liver disorder
Easy way to follow the course of liver diseases
• Limitations
– Poor sensitivity and specificity
– Seldom leads to diagnosis
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5. Interpreting LFTs
the Principles
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6. Broad Principles
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Contextualization
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Normal
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LFT interpretation must be contextualized for each
individual patient
Different labs have different ‘normal’ values
‘Abnormal’ values may be ‘normal’
Patterns
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LFTs rarely provide specific diagnosis
Rather, suggests the general category of liver disorder
through the pattern of abnormal LFT
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7. Normal vs Abnormal
Normal
Abnormal
2 SD
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Normal values = mean ± 2SD of normal population
Normal: 95% of normal, asymptomatic patients have
numbers in this range on a “bell shaped curve”
Abnormal: By definition, 2.5% of normal patients have lab
values either above or below the “normal” range
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8. Patterns of Abnormal LFTs
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Hepatocellular damage: ALT, AST, LDH
Cholestasis: ALP, GGT, bilirubin, bile acids
Biosynthetic function: PT/ INR, albumin, cholesterol
Metabolic function: bilirubin, ammonia, lactate,
glucose, ICG
Clinical scores of decompensation: CPS, MELD
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9. Patterns of Abnormal LFTs
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Hepatocellular damage: ALT, AST, LDH
Cholestasis: ALP, GGT, bilirubin, bile acids
Biosynthetic function: PT/ INR, albumin, cholesterol
Metabolic function: bilirubin, ammonia, glucose, ICG
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Clinical scores of decompensation: CPS, MELD
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10. Interpreting LFTs
the Patterns
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11. Hepatocellular Damage
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12. Markers of Hepatocellular Damage
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ALT & AST most frequently used
Released when hepatocytes damaged
Normal values:
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ALT: 5 – 40 IU/L
AST: 8 – 20 IU/L
Patterns to note:
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AST: ALT ratio
Level of elevation
Rate of decline
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13. ALT vs AST
ALT
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Cytosol
Half life: 47H
Low concentration in
other tissues:
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Skeletal muscle, kidney,
heart
More specific for liver
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AST
Cytosol 20%,
mitochondria 80%
Half life: cytosol 17H,
mitochondria 87H
Other tissues:
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heart, RBC, skeletal
muscle, kidneys,
pancreas, brain, lung
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14. AST: ALT Ratio
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Normal: 0.6 – 0.8
< 1: most liver disorders
> 2:
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Alcoholic hepatitis: AST < 300
Drugs & toxins
Extra-hepatic source
Ischemia
Cirrhosis
Fulminant Wilson’s disease (> 4)
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15. AST: ALT Ratio
90
80
70
60
50
AST/ALT >1
AST/ALT >2
40
30
20
10
0
alcoholic
post necrotic
cirrhosis
chronic
hepatitis
obstructive
jaundice
viral hepatitis

16. Level of Elevation
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ALT > 600 (15x):
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ALT < 200 (5x):
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Acute hepatic injury
Chronic hepatic injury, improved acute injury
ALT 200-600 (5-15x):
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Less useful
Most common scenario!
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17. ALT > 600 (15x)
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Acute viral hepatitis
Acetaminophen
overdose
Ischemic hepatitis aka
shock liver
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Drugs & toxins
Autoimmune hepatitis
Wilson's disease
Acute bile duct obstruction
Acute Budd Chiari
Syndrome
Can cause ALT > 3000
(75x)
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18. ALT < 200 (5x)
ALT Predominant
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Chronic hepatitis B, C
Acute viral hepatitis
NASH
Drugs, toxins
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Autoimmune hepatitis
Metabolic disorders
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AST Predominant
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Almost any liver disease
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Alcoholic liver disease
Drugs, toxins
NASH
Cirrhosis
Non-hepatic source:
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Haemolysis, myopathy,
strenuous exercise
Macro-AST: 15-60% of
tertiary referrals
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19. Rate of Decline
FAST
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Short half life drug
Ischemic hepatitis
Acute biliary tract obstruction
Fulminant hepatitis
SLOW
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Acute viral hepatitis
Long half life drug
Autoimmune hepatitis
Metabolic disorders
Green: Ischemic hepatitis
Blue: Acute viral hepatitis
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20. Cholestasis
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21. Alkaline Phosphatase (ALP)
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Main marker of cholestasis
Normal: 20-70 IU/L
Half life: 7 days
Sources:
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Hepatocytes
Osteoblasts, gut, kidney, placenta
Biliary obstruction:
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Raised levels due to induction of ALP synthesis
May not rise until 1-2 days later
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22. Raised ALP: Causes
Physiologic Causes
 Age > 60 yrs
 Children, adolescents
 Pregnancy
 Blood group O
 Post meal (fatty meal)
Pathologic Causes
 Intrahepatic cholestasis
 Extrahepatic
cholestasis (bile duct
obstruction)
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23. Normal ALP Values vs Age
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24. Raised ALP: Pathologic Causes
Intrahepatic Obstruction
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Drugs
Sepsis
Others
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Infiltrative liver disease
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Primary biliary cirrhosis
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Primary sclerosing
cholangitis (PSC)
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Paraneoplastic syndromes
Extrahepatic Obstruction
 Intraluminal:
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Bile duct wall:
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Gallstones
Cholangiocarcinoma
Extraluminal:
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Pancreatic cancer,
lymph nodes, gallstones
(Mirizzi's Syndrome)
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25. -Glutamyl Transpeptidase (GGT)
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Main utility
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Differentiate ALP source
Not found in bone; not raised in pregnancy/ childhood
Sources: liver, kidney, pancreas, intestine, prostate, spleen,
heart, brain
Half life: 7-10 days; 28 days in alcohol liver injury
Isolated GGT elevation:
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Due to induction of hepatic microsomal GGT
Drugs: warfarin, anticonvulsants, barbiturates
Alcohol: also causes hepatocyte leakage
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26. Biosynthetic Function
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27. Coagulation Factors
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All synthesized in liver except Factor VIII
Mostly present in excess
Prothrombin Time (PT): Factors I, II, V, VII, IX, X
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Half life: Factor VII – 6H (shortest)
Abnormalities only occur when liver's biosynthetic
ability substantially impaired
Common causes:
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Vit K deficiency (malnutrition, malabsorption)
Warfarin
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28. Albumin
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300 – 500 g in body fluid
Synthesis: 15 g/ day
Degradation: 4% daily
Half life: 19 – 21 days
Not reliable indicator of acute liver disease
Not specific
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Depends on nutrition, volume status, vascular integrity,
catabolism, hormones, stool/ urine losses
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29. Hypoalbuminemia
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Decreased synthesis: protein malnutrition, chronic liver
disease, chronic inflammation
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Increased loss: nephrotic syndrome, protein losing
enteropathy
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Increased volume: ascites, over-hydration
Increased turnover: catabolic states, steroids
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Clues: globulin, cholesterol/ TG
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30. Bilirubin
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31. 'Bilirubin' Pathway
RE Cell
Plasma
Heme → UCB
UCB – Albumin
Hepatocyte
UCB + 'gluconate' → CB
Urobilinogen
Stercobilinogen
UCB: Unconjugated bilirubin
CB: Conjugated bilirubin
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32. Bilirubin
Unconjugated Bilirubin
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Indirect bilirubin
Normal: < 0.8 mg/ dL
(< 13.6 µmol/L)
Lipid soluble, water
insoluble
Bound to albumin in plasma
Not filtered by kidney →
not present in urine
Conjugated Bilirubin
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Direct bilirubin
Normal: 0.3 – 1.0 mg/dL
(5.1 – 17.0 µmol/L)
Water soluble, lipid
insoluble
Excreted in bile
Filtered by glomerulus →
majority reabsorbed, small
amount excreted in urine
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33. Isolated Unconjugated Hyperbilirubinemia
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Unconjugated bilirubin > 85% of total bilirubin
Increased production:
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Haemolysis: rarely > 5 mg/dL (85 µmol/L)
Ineffective erythropoiesis: folate/ iron deficiency
Drugs: rifampicin, ribavirin
Resolution of hematoma
Defects in hepatic uptake or conjugation:
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Gilbert's syndrome, Criggler – Najjar syndrome
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34. Conjugated Hyperbilirubinemia
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Conjugated bilirubin > 50% total bilirubin
Cannot differentiate between obstructive &
parenchymal causes
Tea coloured urine + clay coloured stool: usually
cholestatic cause, although parenchymal cause
possible
Malignant obstruction usually higher values
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35. Delta Bilirubin
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Conjugated bilirubin covalently bound to albumin
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Important fraction of total bilirubin in patients with
cholestasis & hepatobiliary disease
Prolonged half life: 19 – 21 days (albumin)
Late recovery phase: all bilirubin may be in this form
Explains 2 enigmas in patients with raised
conjugated bilirubin:
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CB declines slowly in patients who are recovering well
No bilirubinuria during recovery phase as delta bilirubin
not filtered by glomeruli
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36. Summary
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Principles of LFTs:
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Contextualization, Normal Values, Abnormal Patterns
Patterns of Abnormal LFTs
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Hepatocellular injury: ALT, AST
 AST: ALT ratio
 Level of elevation
 Rate of decline
Cholestasis: ALP, GGT
Biosynthetic function: PT, albumin
Bilirubin
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37. Conclusion
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'LFT's are numerous & somewhat confusing
Have limited sensitivity & specificity
Not all liver ds have abnormal LFT
Not all normal LFTs have normal livers
Decrease in values may not mean improvement
What to do?
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All abnormal LFTs should be investigated
LFTs must be contextualized for each patient
Refer when unsure
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38. Thank You
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