Biochemical liver markers

 Liver function tests (also known as a liver panel) are blood tests that measure different enzymes, proteins, and other substances made by the liver. These tests check the overall health of your liver. Transasia offers a wide menu of test parameters in convenient pack sizes in powder and liquid stable formats as well as system packs for Erba range of fully automated analyzers.

The use of serum biochemical tests plays an important role in the diagnosis and treatment of liver diseases. However, an isolated test provides limited information, which must be evaluated in the context of the patient's history and clinical condition. Biochemical liver tests consist of markers of hepatocellular injury (aminotransferases and alkaline phosphatase), liver metabolism tests (bilirubins), and liver synthetic function tests (serum albumin and prothrombin time [PT]).

 

Hepatic injury markers

The liver contains a high concentration of enzymes, some of which are present in serum in very low concentrations. Injury to the hepatocyte membrane leads to leakage of these enzymes into the serum, which results in increased serum concentration within a few hours after liver damage. Serum enzyme tests can be categorized into two groups: enzymes whose elevation reflects widespread damage to hepatocytes (aminotransferases) and enzymes whose elevation reflects primarily cholestasis (Alkaline Phosphatase, gammaglutamyltransferase, or gammaglutamyltranspeptidase - GGT).

Aminotransferases (formerly called transaminases) are sensitive indicators of hepatocyte damage. They consist of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). AST is found, in decreasing order of concentration, in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes. ALT, on the other hand, is present in higher concentration in the liver, thus being a more specific marker for liver injury.

Alkaline Phosphatase represents a group of enzymes present in practically all tissues. It presents four subtypes according to their location (intestinal, placental, liver, bone and kidney). As alkaline phosphatase is present in different tissues, isolated elevations do not always mean liver disease. Bone diseases, small intestine diseases and even pregnancy can cause isolated enlargement. The primary value of serum alkaline phosphatase in diagnosing liver disease is in recognizing cholestatic disease. In patients with cholestasis, alkaline phosphatase is typically elevated to at least four times the upper limit of normal.

GGT is an enzyme present in hepatocytes and biliary epithelial cells, as well as in the kidneys, prostate, pancreas, spleen, heart and brain. It is used to find out if there is any organic lesion, drug and/or medication intoxication, alcohol abuse or diseases of the pancreas.

Lactic dehydrogenase (LDH) is a cytoplasmic enzyme present in tissues throughout the body. This test is not as sensitive as serum aminotransferases in liver disease and has low diagnostic specificity. It is most useful as a marker of hemolysis. It is elevated in cases of ischemic hepatitis and, when accompanied by an elevation of FA-Alkaline Phosphatase, suggests malignant infiltration of the liver.

 

Hepatic metabolism tests

Bilirubins: Rupture of red blood cells releases hemoglobin, which is taken up by the reticulo-endothelial system of the liver, spleen and bone marrow, being transformed by hemeoxygenase into biliverdin. Biliverdin reductase converts biliverdin to free bilirubin. This form of bilirubin is called unconjugated or indirect (BI) and is fat-soluble. BI binds to albumin, the way in which it is transported in plasma, captured by the hepatocyte and transported to the endoplasmic reticulum, where it is converted by the action of the enzyme uridine diphosphataseglucuronosyl-transferase into conjugated or direct bilirubin (BD). BD is transported through the canalicular membrane to the bile, being one of the most susceptible steps to compromise in the presence of liver injury. Once excreted from the hepatocyte into the bile canaliculus, BD is transported via the bile.

 

Increases in BI may be due to increased production, decreased uptake and/or conjugation by the hepatocyte, while increases in BD are usually due to hepatocellular or biliary dysfunction. In the neonatal period, there may be a physiological increase in BI. However, it is recommended to measure total and fractional bilirubin in all children who remain jaundiced after the second week of life. Unlike indirect hyperbilirubinemia, which can be physiological, the elevation of BD is always correlated with pathological states and reflects the decrease in bile secretion due to hepatocellular or biliary disease, that is, cholestasis. Every newborn or infant with BD > 1.0 mg/dL deserves diagnostic investigation.This is a condition that represents an urgency and must be identified early by the pediatrician. The normal concentration of total serum bilirubin is less than 1 mg/dL. The direct fraction corresponding to up to 30% of the total, or 0.3 mg/dL.

 

Liver function tests

Albumin: Albumin is the most abundant plasma protein, accounting for 80% of the plasma osmotic pressure. Due to its long half-life of about 21 days, its levels may not be affected in acute liver diseases such as viral hepatitis or liver failure of any etiology. In cirrhosis or chronic liver disease, low serum albumin can be a sign of advanced liver disease. However, low serum albumin is not specific for liver disease and can occur in other conditions such as malnutrition, infections, nephrotic syndrome, or protein-losing enteropathy. Normal serum albumin concentrations are between 3.5 g/dL and 5.0 g/dL.

Prothrombin time: PT and INR (international normalized ratio) measure the activity of clotting factors I, II, V, VII and X, which are all synthesized in the liver and depend on vitamin K for synthesis. Clotting factors have a much shorter half-life than albumin. Therefore, PT/RNI is the best measure of synthetic liver function in acute settings. Prolongation of PT for more than 5 seconds above the control value (INR > 1.5) is a sign of poor prognosis for liver disease and an important factor in defining liver transplantation priority. It is not a sensitive indicator in chronic liver diseases, as even in cases of severe cirrhosis; levels can be normal or slightly increased. Vitamin K deficiency also causes prolonged labor, which may be due to malnutrition, malabsorption and severe cholestasis with inability to absorb fat-soluble vitamins. Administration of vitamin K can help distinguish vitamin K deficiency from hepatocyte dysfunction, as replacement results in PT correction in vitamin K deficiency but not in liver dysfunction.

 Author,

Gaurav Bhide,

Product Manager – Biochemistry

Transasia Bio-Medicals Ltd.