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Liver Function Tests And Interpretation

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  • Clinical Chemistry
  • 2020-08-06 04:40:07

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The liver performs different kinds of biochemical, synthetic and excretory functions, so no single biochemical test can detect the global functions of the liver.

Liver function tests are a battery of tests for the initial detection and management of liver diseases.
Clinical history and physical examination play an important role to interpret the functions.

Uses of liver function tests

  1. Screening: They are a non-invasive yet sensitive screening modality for liver dysfunction.
  2. They are helpful to recognize the pattern of liver disease.
  3. Assess severity and predict the outcome of certain diseases like primary biliary cirrhosis.
  4. Follow up of certain liver diseases and also helpful in evaluating response to therapy like autoimmune hepatitis.

Limitation of liver function tests

  1. Lack of sensitivity:
    Liver Function Tests may be normal in certain liver diseases.
  2. Lack of specificity and are not specific for any particular disease.
    Except for serum bile acids, the Liver Function Tests are not specific for liver diseases and all the parameters may be elevated for pathological processes outside them.

Classification of liver function tests

A. Tests of the liver’s capacity to transport organic anions and to metabolize drugs
B. Tests that detect injury to hepatocytes. (serum enzyme tests)
C. Tests of the Liver’s biosynthetic capacity

A. Tests of the liver's capacity to transport organic anions and to metabolize drugs.

1. Serum bilirubin

Bilirubin is an endogenous anion derived from hemoglobin degradation from the RBC.
The classification of bilirubin into direct and indirect bilirubin is based on the original van der Bergh method of measuring bilirubin.
Bilirubin is altered by exposure to light so serum and plasma samples must be kept in dark before measurements are made.
When the liver function tests are abnormal and the serum bilirubin levels more than 17µmol/L suggest underlying liver disease.

Types of bilirubin

I. Total Bilirubin: This is measured as the amount, which reacts in 30 minutes after the addition of alcohol. Normal range is 0.2-0.9 mg/dl (2-15µmol/L). It is slightly higher by 3-4 µmol/L in males as compared to females.

II. Direct Bilirubin
This is the water-soluble fraction. Measured by the reaction with diazotized sulfanilic acid in 1 minute and this gives an estimation of conjugated bilirubin. Normal range 0.3mg/dl( 5.1µmol/ L).

III.Indirect Bilirubin
This fraction is calculated by the difference of the total and direct bilirubin and is a measure of the unconjugated fraction of bilirubin.

Diagnostic value of bilirubin levels.

Hyperbilirubinemia results from overproduction/impaired uptake, conjugation Increased conjugated bilirubin: Impaired intrahepatic excretion/regurgitation of unconjugated or conjugated bilirubin from hepatocytes of bile ducts.

Serum bilirubin could be LOWERED by drugs like;

  • Salicylates,
  • Sulphonamides,
  • Free fatty acids

Elevated if the serum albumin increases and the bilirubin shifts from tissue sites to circulation.

Prognostic value of bilirubin levels.
In fulminant hepatic failure, deep jaundice is associated with increased mortality.

2. Urine Bilirubin
The presence of urine bilirubin indicates hepatobiliary disease.
Unconjugated bilirubin is tightly bound to albumin and not filtered by the glomerulus and thus not present in urine.
conjugated bilirubin may be found in urine when the serum bilirubin levels are normal because the renal threshold for conjugated bilirubin is low

3. Urobilinogen
An increase in the urobilinogen in urine is a sensitive indicator of hepatocellular dysfunction.
A good indicator of alcoholic liver damage, well-compensated cirrhosis or malignant disease of the liver. It appears early in urine in viral hepatitis and markedly increased in hemolysis.

Urobilinogen gives a purple reaction to Ehrlich’s aldehyde reagent.
A dipstick containing this reagent allows rough and ready quantification.
Freshly voided urine should be used.

B. Tests that detect injury to hepatocytes( serum enzyme tests)

A. Enzymes detecting hepatocellular necrosis


The aminotransferases or transaminases are specific indicators of hepatocellular necrosis.
These enzymes-

  • Aspartate aminotransferase(AST) /serum glutamate oxaloacetic transaminase-SGOT
  • Alanine aminotransferase( ALT)/serum glutamic pyruvate transaminase-SGPT)

They catalyze the transfer of the á amino acids of aspartate and alanine respectively to the á keto group of ketoglutaric acid.
ALT is primarily localized to the liver but the AST is present in a wide variety of tissues like the heart, skeletal muscle, kidney, brain, and liver.

AST : alanine + α ketoglutarate = oxaloacetate + glutamate
ALT: alanine + α ketoglutarate = pyruvate + glutamate

AST is present in both the mitochondria and cytosol of hepatocytes, ALT is localized to the cytosol.

The cytosolic and mitochondrial forms of AST are true isoenzymes and immunologically distinct.
Large increases in mitochondrial AST occur in serum after extensive tissue necrosis.

Mitochondrial AST is also increased in chronic liver disease.
Virtually no aminotransferases are present in the urine or bile.
Hepatic sinusoids are the primary site for their clearance.

Elevation of aminotransferases
1. Severe elevation ( > 20 Times, 1000 U/L) :
The AST and ALT levels are increased in almost all liver diseases. The highest elevations occur in severe viral hepatitis, drug or toxin-induced hepatic necrosis and circulatory shock.

2. Moderate elevation (3-20 Times): 
They are moderately elevated in acute hepatitis, neonatal hepatitis, chronic hepatitis, autoimmune hepatitis, drug-induced hepatitis, alcoholic hepatitis, and acute biliary tract obstructions.

The ALT is usually more frequently increased as compared to AST except in chronic liver disease.
In uncomplicated acute viral hepatitis, the very high initial levels approach normal levels within 5 weeks of the onset of illness and normal levels are obtained in 8 weeks.
Disproportionately low in patients with Wilson disease.

3. Mild elevation (1-3 Times) :
This is seen in sepsis-induced neonatal hepatitis, extrahepatic biliary atresia (EHBA), fatty liver, cirrhosis, non-alcoholic steatohepatitis(NASH), drug toxicity, myositis, Duchenne muscular dystrophy and even after vigorous exercise

AST: ALT Ratio

The ratio of AST to ALT is of use in Wilson disease, CLD, and alcoholic liver disease and a ratio of more than 2 is usually observed.

The lack of ALT rise is probably due to pyridoxine deficiency.

In NASH the ratio is less than one in the absence of fibrosis on liver biopsy.

In viral hepatitis, the ratio is usually less than one.

The ratio invariably rises to more than one as cirrhosis.

ALT exceeds AST in toxic hepatitis, viral hepatitis, chronic active hepatitis, and cholestatic hepatitis
Falsely low aminotransferase levels seen in patients on long term hemodialysis secondary to either dialysate or pyridoxine deficiency.

Low levels have also been seen in uremia

Other enzymes used to assess hepatocellular damage.

These include glutamate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, and sorbitol dehydrogenase

B. Enzymes that detect cholestasis.

1. Alkaline Phosphatase

Alkaline phosphatases are a family of zinc metalloenzymes, with a serine at the active center; they release inorganic phosphate from various organic orthophosphates and are present in nearly all tissues.

In the liver, alkaline phosphatase is found histochemically in the microvilli of bile canaliculi and on the sinusoidal surface of hepatocytes.

Alkaline phosphatase from the liver, bone, and kidney are thought to be from the same gene but that from the intestine and placenta are derived from different genes.

In healthy people, most circulating alkaline phosphatase originates from liver or bone.
The reference method uses p- nitrophenol phosphate as a substrate, in an alkaline buffer.
Fresh unhemolysed serum is the specimen of choice for the estimation. Heparinized plasma may also be used.

The test should not be done on plasma if citrate, oxalate or EDTA were used as anticoagulants, they form a complex with zinc and the alkaline phosphatase, causing irreversible enzyme inactivation.


Average values with age and are relatively high in childhood and puberty and lower in middle age and higher again in old age.References


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