Liver function tests are biochemical, histological, and sonological tests used to help diagnose and monitor liver disease. One must understand various functions of the liver to understand the different liver function tests.

Functions of the liver

The liver is an essential and most important organ in our body. The largest gland in our body is the liver. The liver weighs approximately 1.5 kg. The liver can regenerate, and this is of great help in case of partial hepatectomy and liver transplantation. These are the major functions of the liver

1. Metabolic function of the liver: Most of the metabolic pathways of carbohydrate, protein, lipid, vitamin, and minerals takes place in the liver.
2. Synthetic function of the liver: The liver is the site of synthesis for plasma proteins like albumin and most of the globulins. Many clotting factors like prothrombin, factor V, VII, IX, and X are synthesized in the liver. Many enzymes expressed by hepatic parenchymal cells and biliary canalicular cells play a significant role in the functioning of the liver.
3. Excretory or secretory function of the liver: Bile is produced in the liver and excreted to the gallbladder where it is stored. Bile contains conjugated bilirubin, bile salts.
4. Detoxification function of the liver: The liver can convert many harmful or toxic substances to less harmful or nontoxic by the liver. For example, toxic ammonia which is released from the alpha-amino group of amino acids as a result of transamination and deamination converted to nontoxic urea in the liver.
5. The storage function of the liver: The liver is the storage site for glucose as glycogen: fat-soluble vitamins and vitamin B12 stored in the liver.

Please watch the below-embedded video to know more about the functions of the liver.

Classification of Liver Function Tests [LFTs]

There are various classifications of liver function tests, commonly known as LFTs. Here I have given the simplest kind, which is done currently to assess the functions of the liver. Based on the functions of the liver, all these tests are classified.

1. LFTs based on the excretory functions of the liver: Serum: total, conjugated, unconjugated bilirubin and urine: bile salts, bilirubin, urobilinogen
2. LFTs based on the synthetic functions of the liver: Serum total protein, albumin, globulin, A/G ratio, and prothrombin time.
3. Enzymes: ALT, AST, ALP, and GGT
4. LFT based on detoxification function of the liver: Blood ammonia
5. Radiological LFTs: USG abdomen, CT scan, MRI
6. Histopathological LFT: Liver biopsy

To know more about the classification of the liver function tests, please watch the below embedded my YouTube video.

LFTs based on the excretory functions of the liver:

One of the essential functions of the liver is conjugation and excretion of bilirubin into the bile. Bile with conjugated bilirubin released into the duodenum in the small intestine, normal bacterial flora converts conjugated bilirubin to colorless urobilinogen. The majority of the urobilin (80 to 90%) oxidized to an orange-colored stercobilin and excreted in the stool. The standard color of the feces is due to the presence of stercobilin. The remaining 10 to 20% of urobilinogen reabsorbed to portal circulation and reach the liver. This recycling process is called enterohepatic circulation. A minimal amount of this reabsorbed urobilinogen enters the systemic circulation and reaches the kidney where it is filtered and excreted in the urine as urobilin. Although conjugated bilirubin is water-soluble, we will not find bilirubin in the urine, but we can detect traces of urobilinogen.

Hyperbilirubinemia and Jaundice

Hyperbilirubinemia is a laboratory diagnosis where serum total bilirubin level exceeds 1mg/dl[17µmol/L]. Hyperbilirubinaemia observed due to an imbalance between bilirubin production and excretion. Excessive hemolysis, liver pathology, and obstruction to the passage of bile lead to this imbalance, thereby causing hyperbilirubinemia. When serum total bilirubin level more than 2 to 3 mg/dL, it diffuses into tissues leading to yellowish discoloration of soft tissues. Jaundice is a yellowish discoloration of the skin, mucous membrane, sclera, and tongue when hyperbilirubinemia exceeds 2 to 3 mg/dL. There are three types of jaundice.

1. Prehepatic or hemolytic jaundice
2. Hepatic or hepatocellular jaundice
3. Posthepatic or obstructive jaundice

Prehepatic or hemolytic jaundice:

Jaundice caused due to reasons before conjugation of bilirubin in the liver is known as prehepatic jaundice. It is usually due to excessive hemolysis. Therefor increased unconjugated bilirubin tries to enter the liver for conjugation.  Since there is no problem with the liver, hepatic parenchymal cells work more efficiently to conjugate bilirubin, but the amount of unconjugated bilirubin formed in excessive hemolysis beyond the capacity of the liver. As there is no obstruction to the flow of bile, whatever excess conjugated bilirubin produced will reach the small intestine and converted to urobilinogen. So, unconjugated hyperbilirubinemia is the typical laboratory feature of prehepatic jaundice besides increased fecal stercobilin and urine urobilinogen.

The most common causes for Prehepatic jaundice are:

• Malaria
• Sickle cell disease
• Thalassemia
• Glucose-6-phosphate dehydrogenase deficiency
• Mismatched  blood transfusion
• Spherocytosis
• Autoimmune diseases

Hepatic or hepatocellular jaundice

In hepatic jaundice, pathology lies in the liver. There is an appreciable amount of hepatocytes damaged. Therefore the liver cannot conjugate all the unconjugated bilirubin entering the liver.  Hence the elevation of serum unconjugated bilirubin. Even though normal hepatic parenchymal cells can able to conjugated bilirubin to some extent but because of obstruction to the bile flow within the microbiliary tree within the liver damaged hepatocytes. This intrahepatic obstruction leads to regurgitation of conjugated bilirubin to circulation, thereby elevation of serum conjugated bilirubin as well. As conjugated bilirubin is water-soluble, it is easily filtered in the kidney hence in the urine. In hepatic jaundice, we will also find bile salts in the urine as a result of intrahepatic obstruction. Sufficient amount of conjugated bilirubin unable to enter the small intestine, there will be decreased fecal stercobilin and urine urobilinogen.

The most common causes for hepatic jaundice are

• Viral hepatitis
• Cirrhosis of liver
• Alcoholic hepatitis
• Hepatotoxic drugs and chemicals

Posthepatic or obstructive jaundice

Posthepatic jaundice is due to extrahepatic obstruction more precisely in the bile duct. This obstruction prevents the passage of conjugated bilirubin from the gall bladder to the duodenum. So, conjugated bilirubin in the bile regurgitates to blood, thereby elevation of serum conjugated bilirubin. The presence of bilirubin and bile salts in the urine; the absence of fecal stercobilin and urine urobilin is also a feature of posthepatic jaundice.

LFTs based on the synthetic function of the liver:

Estimation of plasma proteins and prothrombin time are the most crucial liver function tests based on biosynthetic functions of the liver. Routine laboratory investigations sort under this category are total serum proteins, serum albumin, serum globulins, albumin/globulin ratio, and prothrombin time.

Plasma proteins

The liver is the site for synthesis of almost all plasma proteins except gamma globulins produced by B lymphocytes. The liver exclusively synthesizes albumin, alpha, and beta globulins.

Serum albumin

Albumin is the essential plasma protein and accounts for 55 to 65% of all plasma proteins. Its normal level in blood is 3.5 to 5 g/dL. Its usefulness as a diagnostic marker acute liver disease is minimal as albumin having a long half-life of 20days but a sensitive marker for chronic liver diseases. Hypoalbuminemia is the characteristic feature of chronic liver diseases. One must rule out nephrotic syndrome, malnutrition where we find decreased serum albumin levels also.

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