Most clinicians face a common problem of interpreting abnormalities in liver function tests. This problem has been enhanced with the introduction of automated routine laboratory testing. Commonly available tests are alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP), gammaglutamyl transferase, serum bilirubin, prothrombin time, or international normalised ratio (INR) and serum albumin. They show different functions of the liver, to excrete anions (bilirubin), hepatocellular integrity (transaminases), formation and the consequent free flow of bile (bilirubin and ALP), and protein synthesis (albumin). 

Bilirubin

Bilirubin is formed from the lysis of haem component within the reticuloendothelial system. Unconjugated bilirubin is transported to the liver loosely bound to albumin while conjugated bilirubin is water soluble and appears in urine.

It is conjugated to bilirubin glucoronide within the liver and consequently secreted into bile and the gut respectively. It is further broken into urobilinogen via intestinal flora, out of which some is reabsorbed and either excreted via the kidney into urine or excreted by the liver into the gastrointestinal tract. 

The levels of bilirubin production increases in haemolysis, ineffective erythropoiesis, resorption of a haematoma, and rarely in muscle injury. All of these cases have unconjugated form of bilirubin. Conjugated type of hyperbilirubinaemia is seen in parenchymal liver disease and biliary obstruction.

Unconjugated hyperbilirubinaemia (indirect bilirubin fraction >85% of total bilirubin) occurs in Gilbert’s syndrome. These disorders are characterized by increased bilirubin production or in defects in hepatic uptake or conjugation. It is aggravated by fasting and does not need any specific treatment. Another example is fulminant Wilson’s disease which is also typified by disproportionate isolated unconjugated hyperbilirubinaemia. ALP is also found to be low in such situations. Whereas conjugated hyperbilirubinaemia (direct bilirubin >50% of total bilirubin) occurs in inherited or acquired defects in hepatic excretion. Bilirubin levels have prognostic relevance in alcoholic hepatitis, primary biliary cirrhosis, and in acute liver failure. 

Aminotransferases

AST and ALT are considered as an excellent marker of hepatocellular injury. AST is found in the liver, cardiac muscle skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and red cells. 

ALT, a cytosolic enzyme is found in its highest concentrations in the liver and is more specific to the liver and hepatocellular injury triggers the release of these enzymes into the circulation.

Common causes of abnormalities of these enzymes are non-alcoholic fatty liver disease, alcoholic liver disease, chronic hepatitis B and C, autoimmune liver disease, haemochromatosis, Wilson’s disease, α₁- antitrypsin deficiency, and coeliac disease.

Source: Limdi JK, Hyde GM. Evaluation of abnormal liver function tests. Postgraduate Medical Journal 2003;79:307-312. Available at: https://pmj.bmj.com/content/79/932/307