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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.
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