Liver Function Test

Functions of Liver

  • Synthetic function
    • a. Synthesis of plasma proteins (albumin, coagulation factors, globulins)
    • b. Synthesis of cholesterol
    • c. Synthesis of triacylglycerol
    • d. Lipoprotein synthesis
  • Metabolic function
    • a. Carbohydrates : glycolysis, gluconeogenesis glycogen synthesis and breakdown;
    • b. Fatty acid synthesis and breakdown, Ketogenesis;
    • c. Protein catabolism
    • d. Citric acid cycle, production of ATP
  • Detoxification and excretion
    • a. Ammonia to urea
    • b. Bilirubin (bile pigment)
    • c. Cholesterol
    • d. Drug metabolites
  • Homeostasis: Blood glucose regulation
  • Storage function : Vitamin A, D, K, B12
  • Production of bile salts; help in digestion

Indications for Liver Function Tests

1. Jaundice

2. Suspected liver metastasis

3. Alcoholic liver disease

4. Any undiagnosed chronic illness

5. Coagulation disorders

When to Get Liver Function Test

Classification of liver function tests

A. Classification based on laboratory findings

  • Group I (Tests of hepatic excretory function)
    • i. Serum – Bilirubin (total, conjugated, and unconjugated)
    • ii. Urine – Bile pigments, bile salts and urobilinogen
  • Group II: Liver enzymes (Markers of liver injury/cholestasis)
    • i. Alanine amino transferase (ALT)
    • ii. Aspartate amino transferase (AST)
    • iii. Alkaline phosphatase (ALP)
    • iv. Gamma glutamyl transferase (GGT)
  • Group III: Plasma proteins (Tests for synthetic function of liver)
    • i. Total proteins
    • ii. Serum albumin, globulins, A/G ratio
    • iii. Prothrombin time
  • Group IV: Special tests
    • i. Ceruloplasmin
    • ii. Ferritin
    • iii. Alpha-1-antitrypsin (AAT)
    • iv. Alpha-fetoprotein (AFP)

B. Classification based on Clinical aspects

  • Group I: Markers of liver dysfunction
    • i. Serum bilirubin
    • ii. Urine: Bile pigments, bile salts and UBG
    • iii. Total protein, serum albumin and A/G ratio
    • iv. Prothrombin time
    • v. Blood ammonia
  • Group II: Markers of hepatocellular injury
    • i. Alanine amino transferase (ALT)
    • ii. Aspartate amino transferase (AST)
  • Group III: Markers of cholestasis
    • i. Alkaline phosphatase
    • ii. Gamma glutamyl transferase

Bilirubin (Test of excretory function of liver)

  • Bilirubin is the excretory product formed by the catabolism of heme. It is conjugated by the liver to form bilirubin diglucuronide and excreted through bile.
  • Normal serum bilirubin 0.2-1.0 mg/dl
  • Unconjugated bilirubin 0.2–0.7 mg/dl
  • Conjugated bilirubin 0.1–0.4 mg/dl.
  • The bilirubin is estimated by van den Bergh reaction, where diazotised sulfanilic acid reacts with bilirubin to form a purple-colored complex, azobilirubin.
  • In hemolytic jaundice, unconjugated bilirubin is increased
  • In obstructive jaundice, conjugated bilirubin is increased
  • In hepatocellular jaundice, a biphasic reaction is observed, because both conjugated and unconjugated bilirubins are increased

Urinary Bilirubin

  • In all cases of jaundice, urine should be examined for the presence of bile pigments (bilirubin), bile salts and urobilinogen.
  • In prehepatic jaundice, the unconjugated bilirubin is increased in blood, it does not appear in urine; hence called acholuric jaundice.
  • In obstructive jaundice, conjugation of bilirubin occur but cannot be excreted thru normal path, it is regurgitated back into bloodstream; this is then excreted through urine. So in obstructive jaundice, urine contains bilirubin.

Urinary Urobilinogen

  • Urobilinogen is detected by Ehrlich’s test
    • In cases of obstruction, urobilinogen is decreased or absent in urine
    • In hepatocellular jaundice, urobilinogen is initially elevated, then decreases or disappears
    • In hemolytic anemias, urobilinogen is increased

Urine Bile Salts

  • Normally bile salts (sodium salts of taurocholic acid and glycocholic acid) are present in the bile; but are not seen in urine.
  • Bile salts in urine are detected by Hay’s test.
  • Positive Hay’s test indicates the obstruction in the biliary passages causing regurgitation of bile salts into the systemic circulation leading to its excretion in urine.
  • Obstruction can occur in obstructive jaundice and also in hepatic jaundice due to obstruction of micro biliary channels caused by inflammation.

Tests based on Synthetic Function of Liver

1. Serum albumin level

  • Plasma proteins except immunoglobulins are synthesised by the liver.
  • Serum albumin reflects the extent of functioning liver cell mass.
  • Normal albumin level in blood is 3.5 to 5.0 g/dl

2. Serum globulins

  • Normal globulin level is 2.5 to 3.5 g/dl.
  • They constitute immunoglobulins produced by B lymphocytes as well as alpha and beta globulins synthesized mainly by hepatocytes.
  • Gamma globulins increase in chronic liver diseases (chronic active hepatitis, cirrhosis).
  • In cirrhosis, antibodies against intestinal bacteria are seen.
  • IgG is increased in autoimmune hepatitis.
  • IgM is increased in primary biliary cirrhosis.
  • IgA is increased in alcoholic liver disease.

3. Prothrombin time (PT)

  • Prothrombin is synthesised by the liver and is a useful indicator of liver function.
  • The half-life of prothrombin is 6 hours only; therefore, PT indicates the present function of the liver.
  • PT is prolonged only when liver loses more than 80% of its reserve capacity.
  • In case of liver disease, the PT remains prolonged even after parental administration of vitamin K.

4. Alpha-fetoprotein (AFP)

  • It is a normal component of fetal blood which disappears after birth within a few weeks. It is also a important tumor marker.
  • Mild elevation – chronic hepatitis or cirrhosis
  • Drastic increase – hepatocellular carcinoma, germ cell tumors and teratoma of ovary.
  • AFP is tested by Immuno assay
  • Normal values – up to 1 year < 30 ng/ml
  • adults <15 ng/ml

5. Ceruloplasmin (Cp)

  • It is mainly synthesized by the hepatic parenchymal cells and a small part by lymphocytes.
  • Cp increases in active hepatitis, biliary cirrhosis, hemochromatosis and obstructive biliary disease.
  • Cp decreases in Wilson’s hepatolenticular degeneration

6. Transthyretin (Prealbumin)

  • It is produced by the liver.
  • It has a half-life of 2 days only. Hence it is a useful parameter to assess the hepatic function early during liver disorders.
  • Major function is to transport thyroxine and triiodothyronine.
  • Low levels are seen in acute hepatitis

7. Alpha-1 antitrypsin (AAT)

  • It is an acute phase reactant, synthesized and secreted by liver.
  • AAT inactivates serine proteases (elastase and collagenase).
  • Low levels are associated with neonatal cholestasis, juvenile cirrhosis and micronodular cirrhosis in adults.
  • Increased levels are recorded in acute trauma, infections or after estrogen therapy and in malignancies.

8. Haptoglobin

  • It is synthesized in the liver, transports free hemoglobin in the plasma to reticulo-endothelial system.
  • Low levels are seen in severe hepatocellular liver disease (deficient synthesis) and in hemolytic disease (increased rate of degradation).
  • High levels are seen in inflammatory processes, trauma, infections, and myocardial infarction.

Tests based on Serum Enzymes

(Liver Enzyme Panel)

  • The enzymes used in the assessment of hepatobiliary disease may be divided into two groups:
    • (a) those indicating hepatocellular damage
    • (b) those indicating cholestasis (obstruction)

Enzymes indicating hepatocellular damage

  • ALT – alanine amino transferase (SGPT)
  • AST – aspartate amino transferase (SGOT)
  • Normal value serum ALT – 10-35 IU/L
  • serum AST – 8-20 IU/L
  • Serum ALT and AST are elevated in all liver diseases
  • Very high levels (more than 1000 units) are seen in acute hepatitis (viral and toxic).
  • Elevation of ALT is more in cases of hepatic disease compared to AST.
  • AST elevation is more than ALT in alcoholic liver disease.
  • In alcoholic liver disease, ratio of AST/ALT more than 2 is suggestive.
  • Moderate elevation (100-300 U/L) – alcoholic hepatitis, autoimmune hepatitis, Wilson’s disease and nonalcoholic chronic hepatitis.
  • Minor elevation (100U/L) – chronic viral hepatitis (hepatitis C), fatty liver, non-alcoholic steatohepatitis (NASH).

Markers of Obstructive Liver Disease

Alkaline Phosphatase (ALP)

  • Normal range : 35-110 U/L
  • Very high levels are noticed in patients with cholestasis or hepatic carcinoma. The bile duct obstruction induces the synthesis of theenzyme by biliary tract epithelial cells.
  • In parenchymal diseases of the liver, mild elevation of ALP is noticed. But in hepatitis, ALP level is elevated.
  • Very high levels of ALP (10-12 times of upper limit) are noticed in extrahepatic obstruction (obstructive jaundice) caused by gallstones or by pressure on bile duct by carcinoma of head of pancreas. Intrahepatic cholestasis may be due to virus (infective hepatitis) or by drugs (chlorpromazine).
  • Drastically high levels of ALP (10-25 times of upper limit) are seen in bone diseases such as Paget’s disease (osteitis deformans), rickets, osteomalacia, osteoblastoma, metastatic carcinoma of bone and hyperparathyroidism.

Gamma Glutamyl Transferase (GGT)

  • GGT is clinically sensitive to detect alcohol abuse.
  • GGT level in alcoholic liver disease roughly parallels the alcohol intake.
  • Normal range : 8-38 U/L
  • Elevated levels – in chronic alcoholism, pancreatic disease, myocardial infarction, renal failure, chronic obstructive pulmonary disease and in diabetes mellitus.
  • In liver diseases, GGT elevation parallels that of ALP and is very sensitive of biliary tract disease.

Other Biochemistry Notes

Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

VITAMIN D

. Blood Metabolism (Heme synthesis and breakdown)

Haemoglobinopathies

DNA Repair

Regulation of gene expression

DNA Replication

Transcription

Protein synthesis and genetic code

Detoxification (Xenobiotics)

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