Liver Function Tests

LFTs are:

Proteins and Enzymes:

Proteins:

  • Albumin
  • Coagulation Proteins
  • Immunioglobulins (IgA, IgG)

Enzymes

  • ALT (Alanine Transaminase) (aka Alanine Aminotransaminase)
  • AST (Aspartate Transaminase)
  • GGT (Gamma-glytamyl transpeptidase)
  • ALP (Alkaline Phosphotase)

(ALT and AST are called the aminotransferases)

Hypoalbuminaemia

Can be caused by:

  • Chronic Liver Disease
  • Liver Injury
  • Severe Malnutrition

Impaired Coagulation

Prolonged prothromibin time (PT) implies cholestasis ; what is happening is that the bile isn’t able to reach the duodenum and this prevents the absorption of vitamin K.

 

Cholestasis

Cholestasis is defined as failure of normal amounts of bile to reach the duodenum. 

This may be due to a problem in the main bile ducts – extrahepatic cholestasis 

Or in the liver itself –  intrahepatic cholestasis

What happens inside the liver is that the bile backs up and there is acumulation of bile in the liver cells and bilary passages and there is retention of all the substances usually excreted in the bile.

IgM and IgG

Raised in chronic liver conditions:

  • Primary Biliary Cirrhosis
  • Chronic Autoimmune Hepatitis

ALT and AST

Think of ALT and AST together – aSt, aLt (Sil – window sil)

ALT  – Found in mostly the liver

AST  – Found in the Liver, Skeletal Muscles, Kidneys, Brain

 

***When ALT and AST are up it implies hepatocellular damage.*** (Think of it being Hepato-SIL-ular damage!)

  • can also be raised in cholestasis – but this is very when the cholestasis is causing hepatocellular damage.
  • ALT is more sensitive and specific than ALT, and AST will catch up with ALT and exceed it in chronic liver damage

AST:ALT Ratio And Alcohol

Think of a window SiL (It’s aSt to aLt ratio)

If the AST:ALT ratio is more than 2:1, it’s a 90% chance of alcoholic liver damage

If the AST:ALT ratio is more than 3:1 it’s a 96% chance of alcoholic liver damage

Also likely if GGT is twice normal it’s likely to be alcoholic liver disease – but GGT alone is not enough

Non-Alcoholic Steatohepatitis “Fatty Liver”

  • AST:ALT ratio is typically less than 1
  • ALT and AST are raised but not by more than 4 times

ALP and GGT

 

ALP and GGT come from BILIARY CANALCULI membranes…

So they are raised in biliary outflow obstruction (cholestasis) rather than in hepatocellular damage.

Assume Gallstones or Cancer

 

GGT

  • Good marker when considering hepatobiliary disease
  • If GGT is normal hepatobiliary disease is ruled out

BUT…

GGT is also raised in:

  • pancreatic disease
  • myocardial infarction
  • COPD
  • Renal Failure
  • Diabetes
  • Obesity
  • Alcoholism

ALP

As well as cholestasis it’s also raised in:

  • Bone Destruction
  • 3rd Trimester
  • Growing Children

— so to determine if it is liver or not —

  1. Check other LFTs are normal
  2. Can ask for plasma electrophoresis

Bilirubin

Haem from RBCs and Macrophages is broken down into Bilirubin (a Bile pigment)

It’s then carried in blood as the unconjugated form and bound to albumin

It enters the hepatocytes and is conjugated to form bilirubin diglucuronide

It’s then secreted in the bile.

Causes of Jaundice (raised bilirubin)

  • Prehepatic
  • Intrahepatic
  • Posthepatic

Prehepatic Jaundice:

  • Increased Turnover (LFTs normal)
  • Gilberts

Hepatic Jaundice

  • Failure of hepatocytes to take upmetabolise or excrete bilirubin
  • This implies hepatocellular damage

Post Hepatic Jaundice

  • Failure to offload bilirubin into the duodenum – cholestasis

Clinical Presentations

  1. Jaundice + Pain + Fever = Ascending Cholangitis (infection of biliary tract often due to gallstones, raised ALP)
  2. “The Algias” : myalgia, arthralgia – consider a viral cause, sometimes a drug cause – Raised ALT and AST
  3. Sclerosing Cholangitis: Fibrosis of the biliary tract – raised ALP
    1. Primary – linked with Inflammatory Bowel Disease
    2. Secondary – following surgery  / stone in duct / AIDs
  4. Primary Biliary Cirrhosis – Raised ALP
    1. 95% women
    2. Autoimmune
    3. Age 30 – 65