Liver Function Tests Overview

Liver Function Tests (LFTs)

• LFTs do not measure specific liver function, especially ALT and AST.
• LFT abnormalities are seen late in hepatic disease processes.
• LFT abnormalities reflect hepatocellular injury more than liver function.

Synthetic Function

• Prothrombin Time (PT): Measures activity of clotting factors (fibrinogen, prothrombin, factors V, VII, and X)
  • Normal PT: 11-14 seconds.
  • Prolonged INR usually indicates liver dysfunction.
• Albumin: Evaluates chronic liver disease and hepatocellular function (protein synthesis).
  • Levels below 2.5-3 g/dL generally indicate a more chronic problem.
  • Poor specificity (low levels seen with malnutrition, renal losses, third spacing).
• International Normalized Ratio (INR):
  • Prolonged INR usually indicates liver dysfunction.
  • Effect on coagulation depends on balance between coagulation and anticoagulation factors.
• Serum Cholesterol and Plasma Pseudocholinesterase: These tests are also used in evaluating synthetic function.

Hepatocellular Injury/Hepatic Cellular Integrity

• Aminotransferases (AST and ALT):
  • Serum alanine aminotransferase (ALT): Primarily found in the liver.
  • Aspartate aminotransferase (AST): Found in liver and non-hepatic tissues.
  • Isolated ALT elevation: Indicates non-liver sources (heart, skeletal muscle, brain, kidney, pancreas, adipose tissue, blood).
  • Mild elevation: Any hepatocyte injury (fatty liver, infection).
  • Large elevations: Massive hepatic necrosis, fulminant viral hepatitis, drug-induced liver injury, shock liver.
  • Ratio of AST/ALT: May help differentiate alcoholic liver disease (AST 2-3x greater than ALT).
• Lactate Dehydrogenase (LDH): Nonspecific marker of hepatic injury
  • Extreme elevations seen with ischemia or drug-induced hepatotoxicity (acetaminophen overdose) along with AST/ALT.
  • Extrahepatic disorders can increase LDH (hemolysis, rhabdomyolysis, tumor necrosis, renal infarction, acute stroke).
• Glutathione-S-Transferase (GST): Sensitive for liver injury (short half-life and rises quickly with injury)
  • Can also be used as a marker for improvement.

Cholestatic Disorders

• Hepatic Clearance:
  • Bilirubin: Comes from the breakdown of hemoglobin.
    • Indicates excretory function of the liver.
    • Normal total bilirubin: less than 1.5 mg/dL.
    • Jaundice is usually evident if total bilirubin is greater than 3 mg/dL (repeated twice).
    • Direct bilirubin (conjugated): Water soluble, elevated with bile duct stone or obstruction.
    • Indirect bilirubin (unconjugated): Lipid soluble, elevated with hemolysis or cirrhosis.
• Biliary Duct Obstruction:
  • Alkaline Phosphatase (AP): Mild elevations may be normal.
    • Nonspecific (found in extrahepatic tissues).
    • Values 2-4x normal seen in cholestatic disease.
    • Can indicate intrahepatic or extrahepatic biliary obstruction.
  • Gamma-Glutamyl Transpeptidase (GGT): Used for cholestatic disorders.
  • 5' - Nucleotidase (5'-NT): Used for cholestatic disorders.

Important Note:

• In liver failure, improving values in LFTs may not mean improvement. It could mean there are no more functioning hepatocytes.

Liver Function Tests (LFTs)

• LFTs are not specific measures of liver function, particularly ALT and AST.
• Abnormalities in LFTs often occur late in the progression of hepatic disease.
• LFT abnormalities primarily reflect hepatocellular injury rather than liver function, especially for AST and ALT.
• LFTs are useful for defining the type of liver pathology when combined with clinical assessment.

Synthetic Liver Function

• Liver function tests can evaluate the ability of the liver to synthesize essential substances.
• Prothrombin time (PT) measures the activity of proteins involved in blood clotting (fibrinogen, prothrombin, and factors V, VII, and X).
  • A normal PT range is 11-14 seconds.
  • A prolonged PT can indicate liver dysfunction.
• Albumin synthesis is used to evaluate chronic liver disease and hepatocellular function.
  • Albumin levels below 2.5-3 g/dL may indicate a more chronic liver problem.
  • Albumin levels can be affected by factors like malnutrition, renal losses, and third spacing.
• Other tests that can indicate synthetic liver function include:
  • International Normalized Ratio (INR)
  • Serum Cholesterol
  • Plasma Pseudocholinesterase

Hepatocellular Injury

• Aminotransferases (AST and ALT) are used to assess hepatocellular injury.
  • ALT is primarily found in the liver.
  • AST is found in both the liver and other tissues (heart, skeletal muscle, brain, kidney, pancreas, adipose tissue, blood).
  • Isolated ALT elevations may indicate non-liver sources.
  • Mild elevations of AST and ALT may be seen in mild hepatocyte injury (fatty liver, infection).
  • Large elevations suggest massive hepatic necrosis, fulminant viral hepatitis, drug-induced liver injury, or shock liver.
  • The ratio of AST/ALT can help differentiate alcoholic liver disease, where AST is 2-3 times higher than ALT.
• Lactate dehydrogenase (LDH) is a nonspecific marker of hepatic injury.
  • Extreme LDH elevations are seen with ischemia, drug-induced hepatotoxicity (especially acetaminophen overdose)
  • Other conditions that can elevate LDH include hemolysis, rhabdomyolysis, tumor necrosis, renal infarction, and acute stroke.
• Glutathione-S-transferase (GST) is a sensitive marker for liver injury.
  • It rises quickly after liver injury due to its short half-life.
  • GST levels can also be used to monitor improvement in liver function.

Cholestatic Disorders

• LFTs can help in identifying cholestatic disorders, which involve the impairment of bile flow.
• These disorders affect hepatic clearance and biliary duct obstruction.

Hepatic Clearance

• Bilirubin, a byproduct of hemoglobin breakdown, is used to evaluate the liver's excretory function.
  • A normal total bilirubin level is less than 1.5 mg/dL.
  • Jaundice, a yellowing of the skin and eyes, occurs when total bilirubin exceeds 3 mg/dL on two separate occasions.
  • Direct bilirubin, also called conjugated bilirubin, is water-soluble and increases with bile duct obstruction.
  • Indirect bilirubin, also called unconjugated bilirubin, is lipid-soluble and can be elevated due to hemolysis or cirrhosis.

Biliary Duct Obstruction

• Alkaline phosphatase (AP) levels can be elevated in cholestatic disease.
  • Mild elevations may be normal.
  • AP is a nonspecific marker as it is found in extrahepatic tissues.
  • Values 2-4 times the normal range can indicate intrahepatic or extrahepatic biliary obstruction.
• Gamma-glutamyl transpeptidase (GGT) is also used to assess biliary duct obstruction.
• 5'-Nucleotidase (5'-NT) is another marker helpful in diagnosing cholestatic disorders.

Important Considerations

• In liver failure, improving LFT values may not indicate improvement in liver function. It may mean that there are no more functioning hepatocytes.

Liver Function Tests (LFTs)

• LFTs do not directly measure liver function, they primarily reflect hepatocellular injury.
• Abnormalities in LFTs are often seen late in the progression of liver disease.
• AST and ALT are primarily used to detect hepatocellular injury.
• AST is found in liver as well as other tissues like heart, skeletal muscle, brain, kidney, pancreas, adipose tissue, and blood.
• Isolated ALT elevation generally indicates a non-liver source.
• Mild elevation in AST or ALT can be seen in fatty liver, infection, and other minor hepatocyte injury.
• Large elevations in AST or ALT can indicate massive hepatic necrosis, fulminant viral hepatitis, drug-induced liver injury, or shock liver.
• AST/ALT ratio can help differentiate alcoholic liver disease (AST is 2-3 times greater than ALT).

Synthetic Function

• Prothrombin Time (PT): Measures the activity of fibrinogen, prothrombin and factors V, VII, and X
  • Normal PT is 11-14 seconds.
• Albumin: Evaluates chronic liver disease and hepatocellular function by measuring protein synthesis.
  • Albumin levels less than 2.5-3 g/dL generally indicate a chronic problem.
• International Normalized Ratio (INR): Prolonged INR often indicates liver dysfunction.
  • The effect on coagulation depends on the balance between coagulation and anticoagulation factors.

Hepatocellular Injury

• Lactate Dehydrogenase (LDH):
  • A nonspecific marker of hepatic injury.
  • Extreme elevations are seen in ischemia or drug-induced hepatotoxicity (especially acetaminophen overdose) along with AST/ALT elevation.
  • Extrahepatic disorders like hemolysis, rhabdomyolysis, tumor necrosis, renal infarction, and acute stroke can also increase LDH.
• Glutathione-S-Transferase (GST):
  • A sensitive marker for liver injury due to its short half-life and rapid increase during liver injury.
  • Can also be a marker for improvement in liver function.

Cholestatic Disorders

• Bilirubin: Breakdown product of hemoglobin.
  • Indicates the excretory function of the liver.
  • Normal total bilirubin is less than 1.5 mg/dL.
  • Jaundice is usually evident when total bilirubin is greater than 3 mg/dL on two separate occasions.
  • Direct bilirubin (conjugated) is water soluble and elevated in bile duct stones or obstruction.
  • Indirect bilirubin (unconjugated) is lipid soluble and elevated in hemolysis or cirrhosis.
• Alkaline Phosphatase (AP):
  • Mild elevations can be normal.
  • Non-specific marker as it is also found in extrahepatic tissues.
  • Significant elevation (2-4 times normal) indicates cholestatic disease.
  • Can indicate intrahepatic or extrahepatic biliary obstruction.
• Y Glutamyl Transpeptidase (GTTP):
• 5' - Nucleotidase (5'-NT):

Important Notes:

• Improving values in liver failure do not always indicate improvement. It could mean that there are no more functioning hepatocytes left.
• LFTs are most accurate when interpreted in conjunction with a comprehensive clinical assessment.

This quiz covers key concepts related to Liver Function Tests (LFTs), focusing on their significance in assessing hepatic disease and synthetic functions of the liver. It includes details on prothrombin time, albumin levels, and their relevance to liver dysfunction.