Liver Function Blood Tests provide important biochemical metrics in understanding of underlying hepatic disease process, etiology and prognosis. The commonly used laboratory tests to detect hepatic dysfunction are often referred to as liver function tests or LFT lab tests. Liver has to perform different kinds of biochemical, synthetic and excretory functions, so no single biochemical test can detect the global functions of liver.
Categories of LFT Lab Test
The routine biochemical markers associated with liver function can be classified under 3 basic profiles. These liver profiles are deranged in patients with liver diseases which shows up as abnormal report on blood tests. However, LFT lab tests can be mildly altered in physiological conditions such as pregnancy. You should visit your doctor to correlate clinically in cases of doubt.
1.Test of the liver’s capacity to transport organic anions and to metabolize drugs- Serum bilirubin
2.Tests that detect injury to hepatocytes (serum enzyme tests) – Aminotransferases, Alkaline phosphatase, GGT, 5-Nucleotidase
3.Tests of the Liver’s biosynthetic capacity- Serum proteins albumin, prothrombin time
Bilirubin is an endogenous anion derived from hemoglobin degradation from the RBC. About 30% of serum bilirubin is derived from heme-containing cytochromes or myoglobin. Serum bilirubin consists of 2 fractions i.e conjugated and unconjugated. The rise of each fractions have their own clinical significance.
1.Total bilirubin: This is measured as the amount, which Reacts in 30 minutes after addition of alcohol. Normal range is 0.2-0.9 mg/dl (2-15μmol/L). It is slightly higher by 3-4 μmol/L in males as compared to females.
2. Direct Bilirubin : This is the water-soluble fraction. This is measured by the reaction with diazotized sulfanilic acid in 1 minute. This gives estimation of conjugated bilirubin. Normal range of direct (conjugated) bilirubin is 0.3mg/dl( 5.1μmol/L).
3.Indirect bilirubin: This fraction is calculated by the difference of the total and direct bilirubin. It is a measure of unconjugated fraction of bilirubin. Jaundice can develop from alterations in any step in bilirubin metabolism.
The aminotransferases (formerly transaminases) are the most frequently utilized and specific indicators of hepatocellular necrosis. These enzymes- aspartate aminotransferase(AST, formerly serum glutamate oxaloacetic transaminase-SGOT) and alanine amino transferase( ALT, formerly serum glutamic pyruvate transaminase-SGPT) catalyze the transfer of the alpha amino acids of aspartate and alanine respectively to the alpha keto group of ketoglutaric acid.
ALT is primarily localized to the liver but the AST is present in a wide variety of tissues like the heart, skeletal muscle, kidney, brain and liver. AST is present in both the mitochondria and cytosol of hepatocytes, ALT is localized to the cytosol. The cytosolic and mitochondrial forms of AST are true isoenzymes and immunologically distinct.
The rise of aminotransferases based upon severity can be classified under 3 patterns- mild, moderate and severe. Different patterns are observed in different conditions.
Aminotransferases Ratio (ALT:AST ratio)
The ratio of of ALT and AST elevations helps clinicians to narrow down the differentials to handful of infectious and metabloic etiologies. Some commonly observed biochemical patterns and their causes include:
- AST : ALT >2
-Chronic Liver Diseases (CLD)
-Alcoholic Liver Disease
- AST:ALT <1
-Non alcoholic Steatohepatitis (NASH)
– Toxic Hepatitis
Alkaline Phosphatase (ALP)
Alkaline phosphatases are a family of zinc metaloenzymes and constitute important component of liver function screening profile. In liver, alkaline phosphatase is found in the microvilli of bile canaliculi and on the sinusoidal surface of hepatocytes. Alkaline phosphatase from the liver, bone and kidney are thought to be from the same gene but that from intestine and placenta are derived from different genes.
GGT – Gamma Glutamyl Transpeptidase
Membrane bound glycoprotein which catalyses the transfer of γ glutamyl group to other peptides, amino acids and water. Large amounts are found in the kidneys, pancreas, liver, intestine and prostate. The gene for γ glutamyl transpeptidase is on chromosome 22. GGT levels are high in neonates and infants up to 1 yr and also increase after 60 yr of life. Men have higher values. Children more than 4 yr old have serum values of normal adults. The normal range is 0-30IU/L.
The primary use of serum GGTP levels is to identify the source of an isolated elevation in the serum alkaline phosphatase level. GGTP is not elevated in bone disease. Other conditions causing elevated levels of GGT include uncomplicated diabetes mellitus, acute pancreatitis, myocardial infarction and drugs like phenobarbitone, phenytoin, paracetamol, tricyclic antidepressants.
5′-Nucleotidase (5′NT) is associated with the canalicular and sinusoidal plasma membranes. Its function is undefined. 5′NT is also found in the intestine, brain,heart, blood vessels, and endocrine pancreas. Primary role of the serum 5′NT level is to identify the organ source of an isolated serum alkaline phosphatase elevation. The 5′NT level is not increased in bone disease and is primarily increased in hepatobiliary disease.
The liver is the major source of most the serum proteins. The parenchymal cells are responsible for synthesis of albumin, fibrinogen and other coagulation factors and most of the alpha and beta globulins.Albumin is quantitatively, the most important plasma protein. Normal level is 3.5g/dl to 4.5 g/dl. Accounts for 75% of the plasma colloid oncotic pressure. Albumin are synthesized exclusively by hepatocytes.
The serum albumin levels are typically depressed in patients with cirrhosis and ascites. Albumin synthesis is affected not only in liver disease but also by nutritional status, hormonal balance and osmotic pressure. Corticosteroids and thyroid hormone stimulate albumin synthesis. Albumin levels below 3g/dl in hepatitis should raise the suspicion of chronic liver disease like cirrhosis which usually reflects decreased albumin synthesis. Causes of Hypoalbuminemia other than Liver Disease include Protein malnutrition, Nephrotic syndrome and Chronic protein losing enteropathies.
The prothrombin time is a measure of the rate at which prothrombin is converted to thrombin. The international normalized ratio (INR) is used to express the degree of anticoagulation on warfarin therapy. NR standardizes prothrombin time measurement according to the characteristics of the thromboplastin reagent used in a particular laboratory. Causes of Prolonged PT are decreased hepatic synthetic function, congenital deficiency of clotting factors, Vitamin K deficiency and Disseminated intravascular coagulation (DIC). It is also a component of the Child-Pugh score for chronic liver disease and the MELD score used to assess prognosis.
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- Harrison Principles of Internal Medicine 19th Edition
- Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 9th Edition
- Giannini et al. Liver enzyme alteration: a guide for clinicians, JAMC • 1er FÉVR. 2005; 172 (3)
- R. Thapa and Anuj Walia, Liver Function Tests and their Interpretation, Indian J Pediatr2007; 74 (7) : 663-671