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Chapter 5: Clinical 189
Investigations and procedures Obstruction
Bilirubin: Raised bilirubin levels indicate abnor-
Liver function testing malities in its synthesis, metabolism or excretion.
It often rises in causes of obstructive (cholestatic)
Liver function testing includes blood tests to look for ev-
jaundice, but it is not specific for obstruction or
idence of hepatocyte necrosis, as well as assessing the
even for liver disease (see Table 5.2 and page 185).
actual functions of the liver, i.e. its synthesis of pro- ALP: This enzyme is found in the liver, where it is
teins including albumin and clotting factors and bile
produced by the cells lining the small bile ducts. It
metabolism and excretion. In most laboratories, if liver
is also found in bone, placenta and intestine. If the
function tests (LFTs) are requested, this means mea-
liver disease is primarily due to obstruction of the
surement of the serum levels of bilirubin, aminotrans-
intrahepaticorextrahepaticbileducts(cholestatic),
ferases, alkaline phosphatase (ALP) and total protein.
theALPrisesfirstandproportionallymorethanthe
γ -glutamyl transpeptidase (γ -GT) may be included
aminotransferases.
amongst the standard tests, but often needs to be re-
If the ALP is raised due to liver disease, γ -GT mea-
quested separately. For assessing the synthetic function
surement is also raised as it shares a similar pathway
of the liver, two other blood tests are needed, the pro-
of excretion. If γ -GT levels are normal with a raised
thrombin time and serum albumin.
ALP then a non-hepatic cause should be suspected
Hepatocyte necrosis/damage
such as bone disease. Alternatively, it is possible to
Aminotransferases: Two are measured, aspartate
differentiate the bone and liver isoenzymes.
aminotransferase (AST) and alanine aminotrans-
γ -GT: Alcohol and drugs such as phenytoin induce
ferase (ALT). These are raised by most causes of
this enzyme even when there is no liver damage. It
liver disease, but paradoxically, in severe necrosis
may be used to detect if patients continue to drink
or in late cirrhosis levels may fall to normal in-
alcohol,butitdoeshavealonghalf-life.Incholesta-
dicating a lack of viable hepatocytes. ALT is more
sis it rises in parallel with the ALP.
specific than AST, the latter being found in many
Synthetic function
other organs (see Table 5.2). Serum proteins:
The liver synthesises many proteins. Total pro-
Table 5.2 Non-hepatic causes of abnormal liver
function tests tein itself is not that useful, without measuring
the serum albumin level and immunoglobulin
Blood test Non-hepatic causes
levels.
AST Myocardial infarction Albumin constitutes about 65% of the total pro-
Congestive cardiac failure
Muscle injury (e.g. polymyositis, teinandasithasashorthalf-lifeofabout3weeks,
rhabdomyolysis) it is a good marker of synthetic function. It falls
Haemolysis in both acute and chronic liver disease, although
Bilirubin Haemolysis levels may be normal early in the disease. Low
Sepsis albuminlevels(hypoalbuminaemia)mayleadto
ALP Pregnancy (normal)
Bone disease (e.g. Paget’s disease, the development of ascites and oedema. Other
osteomalacia, metastases, causes of hypoalbuminaemia include gastroin-
hyperparathyroidism) testinal losses or heavy proteinuria.
γ -GT Alcohol Serum immunoglobulins are often non-
Enzyme-inducing drugs
Albumin Malnutrition specifically raised in liver disease. IgM is
Nephrotic syndrome particularly raised in primary biliary cirrhosis,
Congestive cardiac failure whereas IgG is raised in autoimmune hepatitis.
PT Anti-coagulant use Prothrombin time (PT): Most clotting factors are
Dietary deficiency or gastrointestinal synthesised by the liver. They have a much shorter
loss of vitamin K half-life than albumin, and a prolonged PT may
Disseminated intravascular coagulation
occur in both acute and chronic liver disease.