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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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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.

General approach

  • Patients with hepatocellular process, have higher elevations in the serum aminotransferases compared to alkaline phosphatase. However, patients with cholestatic process have the opposite lab findings.
  • The elevated serum bilirubin is a non-specific finding and can be elevated in both hepatocellular and cholestatic conditions.
  • The presence of bilirubin in the urine reflects direct hyperbilirubinemia and hepatobiliary disease.
  • Unconjugated bilirubin is tightly bound to albumin and is not filtered by the glomerulus. Thus, presence of unconjugated bilirubin in urine suggest an underlying kidney disease.
  • Conjugated bilirubin may be found in the urine when the total serum bilirubin concentration is normal. This is so, because the renal capacity for resorption of conjugated bilirubin is low. Additionally, the methods used can detect urinary bilirubin as low as 0.05 mg/dL. Thus, bilirubinuria can be an early sign of liver disease.
  • A low albumin suggests a chronic process such as cirrhosis or cancer, while a normal albumin suggests a more acute process such as viral hepatitis or choledocholithiasis.
  • Elevated Prothrombin time suggests either vitamin K deficiency, malabsorption of vitamin K or significant hepatocellular dysfunction. Failure in correction of prothrombin time with parenteral vitamin K indicates severe hepatocellular injury.
  • Approach to mild (less than 4 times the upper limit of normal) chronic (≥ 6 months) elevation in aminotransferase:
    • Medications - Nonsteroidal anti-inflammatory drugs, acetaminophen, antibiotics, statins, antiepileptic drugs, and antituberculous drugs, herbal preparations and illicit drug. Drugs as a cause for elevation of aminotransferases can be suggested by: lack of symptoms and lab abnormalities prior to consumption of the drug, and improvement in these once the drug is withdrawn.
    • Alcoholism - An AST to ALT ratio of 2:1 or greater is suggestive of alcohol abuse. Of note, a similar AST/ALT ratio can also be seen in nonalcoholic steatohepatitis, and hepatitis C with development of cirrhosis. A 2 fold elevation of the gamma glutamyltransferase (GGT) in patients whose AST to ALT ratio is greater than 2:1 strongly suggests alcohol abuse.
    • Assess for hepatitis B and C - The risk for Hepatitis B & C is increased in patients with history of IV drug use, transfusion, and in patients from parts of the world where a high disease prevalence exists (eg, Southeast Asia, and sub-Saharan Africa). The following tests should be ordered in patients with suspected Hepatitis B: Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (HBcAb)
    • Assess for hemochromatosis, and fatty liver.

Standard liver panel

Measurement Significance Reference range
Albumin (Alb) Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein; the remaining fraction is called globulin (including the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to hypoalbuminaemia. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function, coagulation factors (see below) are much more sensitive. 3.9 to 5.0 g/dL [1]
Alanine transaminase (ALT) Alanine transaminase (ALT), also called Serum Glutamic Pyruvate Transaminase (SGPT) or Alanine aminotransferase (ALAT) is an enzyme present in hepatocytes (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 paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). 8 to 37 IU/L [1]
Aspartate transaminase (AST) Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate 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 skeletal 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. 10 to 34 IU/L [1]
Alkaline phosphatase (ALP) Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis 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). 44 to 147 IU/L [1]
Total bilirubin (TBIL) Bilirubin is a breakdown product of heme (a part of haemoglobin 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, conjugated (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:

  • 1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.
  • 2. 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.
  • 3. Posthepatic: Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or outside the liver.)
Direct bilirubin The diagnosis is narrowed 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 unconjugated bilirubin, and the location 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.
Gamma glutamyl transpeptidase (GGT) Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (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 laboratories, GGT is not part of the standard LFTs and must be specifically requested. 0 to 51 IU/L [1]

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 out.

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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