Liver function test interpretation

Liver function tests (LFTs) are an almost routine laboratory investigation in hospitalised patients but are commonly misinterpreted. They are probably most commonly ordered in the evaluation or right upper quadrant abdominal pain (or abdominal pain generally) but may be ordered without any specific indication often leading to confusion when the results are returned abnormal. Liver function tests usually include Gamma glutamyl transferase (GGT) Alkaline phosphatase (ALP) Alanine transaminase (ALT) Aspartate transaminase (AST) Bilirubin Albumin Total protein

In some ways, however, LFTs is a misnomer because the most closely scrutinised tests (the enzymes GGT, ALP, AST and ALT) do not really reflect liver function at all, rather they reflect liver and/biliary tract damage. In fact, liver function is probably best tested by a coagulation profile or prothrombin time (PT)/international normalised ratio (INR) in the short-term, albumin in the long term and bilirubin. Furthermore the enzyme LFTs are not entirely sensitive or specific for the liver. One of the most useful way to approaching the interpretation of LFTs, like everything in medicine, is by being systematic. Consider what the LFTs actually represent: Enzymes (GGT, ALP, AST, ALT) When enzymes are tested in the blood one is usually looking for damage to a particular tissue and this is the case with the LFTs as well. A predominant rise in GGT or ALT is called a cholestatic pattern because it suggests damage to the biliary tract from cholestasis (or stasis of bile). A cholestatic pattern only really exists if the two are elevated together, isolated rises in either ALP or GGT suggest a different condition. In biliary tract obstruction, one would expect GGT and ALP levels >500. GGT rise in isolation typically occurs through enzyme induction, e.g. through alcoholism or use of anticonvulsants. Typically GGT won't rise above 200IU/L in that setting ALP rises in isolation are fairly non-specific, they can suggest bony disorders like Paget's disease, bony metastases (cancer spread to the bone), or a fracture, but levels also go up in normal pregnancy and with ovarian pathology

A predominant rise in ALT or AST is called a transaminitis pattern and more specifically suggests damage to the liver. There are two things to consider when these enzymes are raised together, (1) how high have they gone/are they going, and (2) what is the ratio? Levels > 1000 suggest major liver injury which occurs with an acute viral hepatitis, drug (e.g. paracetamol) overdose, ischaemic hepatitis or, in very severe cases, autoimmune hepatitis Leves ~100 are more typical of a chronic liver condition like alcoholic hepatitis or chronic viral hepatitis but can also occur as an adverse drug reaction or through a viraemia Levels ~500 can occur with biliary pathology, or with an acute on chronic picture (say an alcohol binge in a patient with chronic and decompensating hepatitis). Another possibility is autoimmune hepatitis.

The ratio is important because it can suggest a specific disease process. Classically an AST:ALT ratio of 2:1 suggests alcoholism and this is thought to be related to malnutrition (in particular Vitamin B6, pyridoxine, deficiency). This can be useful in differentiating alcoholic steatohepatitis from non-alcoholic steatohepatitis (NASH) wherein the ratio is usually < 0.8. Where AST is raised higher than ALT, this is also a marker of severity in liver cirrhosis

Bilirubin is a normal physiological break down product of red blood cells. It is included as a liver function test because it is a measure of the liver's ability to metabolise and excrete this substance (similar to creatinine in the kidney). Rises in bilirubin are best considered with the same system as for jaundice, that is, pre-hepatic, hepatic or post-hepatic. An isolated rise in bilirubin may represent the presence of Gilbert's syndrome, a hereditary predisposition to hyperbilirubinaemia through reduced conjugation ability that is worse with a viral-like illness

Albumin is the predominant plasma protein and determinant of plasma volume. It is useful as a measure of synthetic function of the liver (since the liver produces albumin) but with a half-life of about 3 weeks it demonstrates this function over the long-term. Albumin may also fall as part of the acute-phase inflammatory response, e.g. to an infection like sepsis

In contrast to albumin, prothrombin time/international normalised ratio is a marker of the synthetic function of the liver in the shorter term (half-life of 1-3 days) even though it is not typically considered as part of the LFTs. Other causes of an elevated PT/INR would include the use of warfarin or vitamin K deficiency (e.g. with malabsorption).