Liver Disease: Liver Function Tests

Liver Function Tests
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Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. Most liver diseases cause only mild symptoms initially, but it is vital that these diseases be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed by a medical technologist on a patient's serum or plasma sample obtained by phlebotomy. Some tests are associated with functionality (eg. albumin); some with cellular integrity (eg. transaminase) and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline phosphatase).

Standard liver panel
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Measurement......Significance..........................Reference range
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Alanine trans-.....Alanine transaminase.............5 to 40 IU/L
aminase (ALT)....(ALT), also called
.........................Serum Glutamic Pyru-
.........................vate Transaminase(SGPT)
.........................or Alanine aminotrans-
.........................ferase (ALAT) is an
.........................enzyme present in Hepato-
.........................cytes(liver cells). When
.........................a cell is damaged, it
.........................leaks this enzyme into
.........................the blood, where it is
.........................measured. ALT rises
.........................dramatically in acute
.........................liver damage, such as
.........................Viral hepatitis or Para-
.........................cetamol toxicity(acetamin-
.........................ophen) overdose. Elevations
.........................are often measured in multi-
.........................ples of the upper limit of
.........................normal (ULN).

Measurement......Significance..........................Reference range
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Aspartate tran-...also called Serum...................10 to 40 IU/L
saminase (AST)..Glutamic Oxaloatate
.........................Transaminase(SGOT) or aspar-
.........................tate aminotransferase.(ASAT)
.........................is similar to ALT in that it
.........................is another enzyme associated
.........................with liver parenchymal cells.
.........................It is raised in acute liver
.........................damage, but is also present in
.........................red cells, and cardiac and skel-
.........................etal muscle and is therefore not
.........................specific to the liver. The ratio
.........................of AST to ALT is sometimes useful
.........................in differentiating between causes
.........................of liver damage.

Measurement......Significance..........................Reference range
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Alkaline phos-....is an enzyme in the cells........30 to 120 IU/L
phatase(ALP).....lining the biliary ducts
.........................of the liver. ALP levels in plasma
.........................will rise with large bile duct
.........................obstruction, intrahepatic chole-
.........................stasis or infiltrative diseases of
.........................the liver. ALP is also present in
.........................bone and placental tissue, so it is
.........................higher in growing children (as their
.........................bones are being remodelled) and
.........................elderly patients with Paget's disease

Measurement......Significance..........................Reference range
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Total bilirubin......Bilirubin is a breakdown...........2 - 14 μmol/L
(TBIL).................product of heme(a part of haemo-
.........................globin in red blood cells). The
.........................liver is responsible for clearing
.........................the blood of bilirubin. It does this
.........................by the following mechanism: bilirubin
.........................is taken up into hepatocytes, conju-
.........................gated (modified to make it water-
.........................soluble), and secreted into the bile,
.........................which is excreted into the intestine.
.........................Increased total bilirubin causes
.........................jaundice, and can signal a number of
.........................problems:

Prehepatic: Increased bilirubin production. This can be due to a number of
causes, including hemolytic anemias and internal hemorrhage.
Hepatic:
Problems with the liver, which are reflected as deficiencies in bilirubin
metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin,
and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis
and viral hepatitis.
Posthepatic: Obstruction of the bile ducts,
reflected as deficiencies in bilirubin excretion. (Obstruction can be located
either within the liver or Bile duct outside the liver.)

Measurement......Significance..........................Reference range
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Direct bilirubin....The diagnosis is narrowed.......0 - 4 μmol/L
.........................down further by looking at
.........................the levels of direct bilirubin.
.........................If direct (i.e. conjugated)
.........................bilirubin is normal, then the
.........................problem is an excess of unconju-
.........................gated bilirubin, and the loca-
.........................tion of the problem is upstream
.........................of bilirubin excretion. Hemolysis,
.........................viral hepatitis, or cirrhosis can
.........................be suspected. If direct bilirubin
.........................is elevated, then the liver is
.........................conjugating bilirubin normally, but
.........................is not able to excrete it. Bile
.........................duct obstruction by gallstones or
.........................cancer should be suspected.

Measurement......Significance..............................Reference range
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Gamma glutamyl.Although reasonably specific to....0 to 51 IU/L
transpeptidase...the liver and a more sensitive
(GGT)................marker for cholestatic damage
.........................than ALP, Gamma glutamyl transpep-
.........................tidase(GGT) may be elevated with
.........................even minor, sub-clinical levels of
.........................liver dysfunction. It can also be
.........................helpful in identifying the cause
.........................of an isolated elevation in ALP.
.........................GGT is raised in alcohol toxicity
.........................acute and chronic). In some labora-
.........................tories, GGT is not part of the
.........................standard LFTs and must be specifi-
.........................cally requested.
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Other tests commonly requested alongside LFTs:

5' nucleotidase (5'NTD)
5' nucleotidase is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.
Coagulation tests (e.g. INR)
The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.
It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.
Serum glucose (BG, Glu)
The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.
Lactate dehydrogenase (LDH)
Lactate dehydrogenase is an enzyme found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage.

References
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