Liver function tests
Content
• Liver
function tests
• Normal
reference ranges of various lab parameters
• Various
disease conditions correlated with liver function tests
Objective
After completion of this lecture, student will be able
to:
• Explain
the various liver function tests
• Explain
the normal reference ranges of various lab parameters
• Explain
the various disease conditions correlated with liver function tests
Functions of liver
Introduction
• Tests include:
a)
Tests to assess liver synthetic capabilities
b) Tests to assess cholestatic disease and hepatocellular injury
Tests to assess liver synthetic capabilities
• Used to assess functional
capabilities of liver
• Its synthetic products are measured
[albumin, fibrinogen, prothrombin, hepatoglobin, transferin and other proteins]
• Most commonly used tests include
-albumin
-prothrombin
time
• Occasionally
-total protein
-globulin (with
albumin)
• Albumin:
Reference range: 3.5 to 5 gms/dl
-Synthesised from AA derived
from gut/breakdown of RBC
-Maintains oncotic pressure
-Binds numerous hormones,
anions, drugs and fatty acids
-Liver synthesise 122 gm /day if
needed it can double the synthesis
-Serum half-life is 20 days
-Albumins measurements are slow
to fall after the onset of hepatic dysfunction due to long half –life
-Complete cessation of albumin
production results in only 25% decrease in serum concentration after 8 days
-Albumin concentration remains
unaltered in many liver disease when liver function is preserved – if disease
progress its synthetic capacity impaired [severe hepatitis, cirrhosis]
• Non hepatic causes: Hypoalbuminemia: Malnutrition, malabsorption,
overhydration, nephrotic syndrome, protein losing enteropathy, burns and
chronic illness
• At very low concentration (2-2.5gm/dl)
patients can develop peripheral edema, ascities or pulmonary edema
• Non hepatic causes:
-Hyperalbuminemia:
-Dehydration
-Anabolic steroids
Does not cause any symptoms
• Prothrombin time:
-It is one of the coagulation
factor
-Liver synthesises SIX
coagulation factors: I, II, V, VII, IX and X
Normal range: 10 to 13 seconds
-PT is not specific for liver
disease
Causes for prolongation of PT:
- Inadequate vitamin K in the
diet
- Poor / inadequate nutrition
- Drugs – warfarin, salicylates,
moxalactum, cefoperazone, tetracycline
• If PT remains prolonged despite
parenteral vitamin K (10mg), it is considered a sign of substantial hepatic
dysfunction
• Treat the patient with vitamin K if
no bleeding
• If bleeding present, treat with
fresh frozen plasma
• Total protein:
Reference range: 5.5 to 9gm/dl
-Refers to sum of albumin and
globulin
-Any symptoms increase either
albumin/ globulin also increases total protein
-Its value is limited if albumin
and globulin results are already known
• Globulin:
Reference range: 2 to 3gm/dl
-Refers to total measurements of
immunoglobulins (antibodies) in serum
-Synthesised by T lymphocytes
-Ig – IgA, IgD, IgE, IgE, IgG
and IgM
• Causes:
-Malabsorption
-Protein binding enteropathy
-Hepatocellular dysfunction does
not lower globulin concentration unless associated with malabsorption
-Elevation of globulins is a
sign of inflammation – may present in hepatitis
-In chronic hepatitis - albumin decreases and globulin increases
-In primary biliary cirrhosis –
Increase in IgM
-Alcoholic patients – increase
IgA
• Non – hepatic causes:
-Chronic infections, chronic
inflammatory states, multiple myeloma
-In non-hepatic condition – globulin increases than albumin concentration and thus G;A ratio will be >1 (normal – 0.6)
Tests to assess cholestatic disease and hepatocellular injury
• Liver disease:
-Cholestatic
-Hepatocellular
damage
-Mixed
• Cholestatic –
primary interference with the metabolism or secretion of bilurubin
• Hepatocellular damage – damage to hepatocytes or inflammation of hepatocytes
• Mixed type is due to:
back pressure
Cholestatic <---------------->hepatocellular
damage
swelling
• Elevation of liver enzymes are
common findings in clinical practice
• The significance of the elevation
has to be assessed whether or not mild non-specific elevation (e.g., viral /
drug / liver disease)
Useful tests
Enzymes Reference range
ALP 30 – 120
U/L
GGT 0 - 30U/L
AST 0 – 35
U/L
ALT 0 – 35
U/L
LDH 110 – 220 U/L
Bilurubin
total 2
- 18 mmol/L
direct
(conjugated) 0 - 4
mmol/L
Albumin 3.5 – 5.0 gms/dl
Globulin 2.0 – 3.0 gms/dl
Prothrombin
time 10 – 13 seconds
Liver enzymes are most useful in differentiating hepatocellular damage from cholestasis
Extra-cellular (present
in cells lining biliary canaliculi)
1. ALP
2. GGT
Intra-cellular
enzymes (present in cytosol of liver cells)
1. AST
2. ALT
3. LDH
CHOLESTASIS
Intra-hepatic (obstruction
in bile ducts within liver)
Causes:
– metastasis
Extra-hepatic (obstruction
in bile ducts outside the liver)
Causes:
– gall
stones
– cancer
of head of pancreas
– inflammation
á
ALP & GGT Bone disorder (pagets disease, osteomalacia, 10, 20
malignancy of bone)
á GGT (100-140 U/L) without
any abnormality in liver à Chronic alcoholism or phenytoin
• If
chronic alcoholism is associated with hepato-cellular damage, ALT increase
along with GGT
• Chronic
alcoholism can lead to fatty infiltration, alcoholic hepatitis and cirrhosis
Hepatocellular damage
• In
hepatocellular damage, AST, ALT and LDH increases
• Both
AST and ALT runs parallel
• Measure
ALT as it is very specific to liver
Causes:
– Paracetamol overdose, ischemic / hypoxic
hepatitis
Marked elevation of ALT and LDH, both of the same order (800-3000 U/L)
The ratio of ALT / LD is 0. 8 - 1.2
– Viral hepatitis
–
both ALT and LDH increases
–
ALT elevation is significantly > LDH
–
ALT/LDH ratio is 1.2-2.0
– Infections mono-nucleousis (Epstein Bar
virus)
– Liver
and Spleen maybe swollen
– Simultaneous
increased level of ALP, GGT, LDH and ALT between (200-600 U/L) occur
– Rhabdomylosis
– LD
level will be markedly elevated (800-20,000 U/L) than ALT
– ALT:
LDH ratio is < 0. 8
– Due
to muscle destruction CK level also increase (2,000 – 1,00,000 U/L)
– Increase
CK does not occur in liver damage (liver does not contain CK)
Drugs involved in liver disorders
• Predominantly hepatocellular
– Allopurinol,
aspirin, cytotoxic, diclofenac, anti TB drugs, methotrexate, paracetamol,
phenytoin, propylthiouracil and quinidine
•
Predominantly
cholestasis
– Augmentin,
CBZ, chlorpromazine, chlorpropamide, flucloxacillin, dicloxacillin,
indomethacin, phenothiazines and tolbutamide
• Mixed
– Methyldopa,
halothane, norfloxacin, PAS, ranitidine, sulindac, valproate co-trimaxozole
Summary
• Liver function tests include tests
which assess the liver synthetic capabilities and hepatocellular injury
• Hepatocellular dysfunction does not
lower globulin concentration unless associated with malabsorption
• Hepatocellular damage – damage to
hepatocytes or inflammation of hepatocytes
• The significance of the elevation
has to be assessed whether or not mild non-specific elevation (e.g., viral /
drug / liver disease)
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