Step 3- Assess hepatic function

The liver’s main synthetic functions include:

- Conjugation and elimination of bilirubin

- Synthesis of albumin

- Synthesis of clotting factors

- Gluconeogenesis

- Investigations that can be used to assess synthetic liver function include:

- Serum bilirubin

- Serum albumin

- Prothrombin time (PT)

- Serum blood glucose

 

Bilirubin is a breakdown product of haemoglobin. Unconjugated bilirubin is taken up by the liver and then conjugated. Hyperbilirubinaemia may not always cause clinically-apparent jaundice (usually visible >60 umol/l). The patient’s symptoms and clinical signs can help differentiate between conjugated and unconjugated hyperbilirubinaemia. Unconjugated bilirubin is water-insoluble and therefore doesn’t affect the colour of the patient’s urine. Conjugated bilirubin, however, can pass into the urine as urobilinogen, causing the urine to become darker. ¹

In a similar fashion, the colour of the stools can be used to differentiate the causes of jaundice. If bile and pancreatic lipase’s are unable to reach the bowel because of a blockage (e.g. in obstructive post-hepatic pathology), fat is not able to be absorbed, resulting in stools appearing pale, bulky and more difficult to flush.

The combination of the colour of urine and stools can give an indication as to the cause of jaundice:

Normal urine + normal stools = pre-hepatic cause

Dark urine + normal stools = hepatic cause

Dark urine + pale stools = post-hepatic cause (obstructive)

 

Causes of unconjugated hyperbilirubinaemia include:

- Haemolysis (e.g. haemolyticanaemia)

- Impaired hepatic uptake (drugs, congestive cardiac failure)

- Impaired conjugation (Gilbert’s syndrome)

Causes of conjugated hyperbilirubinaemia include:

- Hepatocellular injury

- Cholestasis

 

Albumin is synthesised in the liver and helps to bind water, cations, fatty acids and bilirubin. It also plays a key role in maintaining the oncotic pressure of blood.

Albumin levels can fall due to:

- Liver disease resulting in a decreased production of albumin (e.g. cirrhosis)

- an acute phase of inflammation which temporarily decreases the liver’s production of albumin

- Excessive loss of albumin due to protein-losing enteropathies or nephrotic syndrome

 

Prothrombin time (PT) is a measure of the blood’s coagulation tendency, specifically assessing the extrinsic pathway. In the absence of other secondary causes such as anticoagulant drug use and vitamin K deficiency, an increased PT can indicate liver disease and dysfunction. The liver is responsible for the synthesis of clotting factors, therefore hepatic pathology can impair this process resulting in an increased prothrombin time.

 

The ALT/AST ratio can be used to determine the likely cause of LFT derangement:

ALT > AST is seen in chronic liver disease

AST > ALT is seen in cirrhosis and acute alcoholic hepatitis

 

Gluconeogenesis is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. The liver plays a significant role in gluconeogenesis and therefore assessment of serum blood glucose can provide an indirect assessment of the liver’s synthetic function. Gluconeogenesis tends to be one of the last functions to become impaired in the context of liver failure.

 

Step 5- Common patterns of LFT derangement

The table below demonstrates the typical LFT patterns associated with acute hepatocellular damage, chronic hepatocellular damage and cholestasis. A single arrow (↑) refers to a mild impairment and a double arrow (↑↑) refers to severe impairment.

           

	Acute hepatocellular damage	Chronic hepatocellular damage	Cholestasis
ALT	↑↑	Normal or ↑	Normal or ↑
ALP	Normal or ↑	Normal or ↑	↑↑
GGT	Normal or ↑	Normal or ↑	↑↑
Bilirubin	↑ or ↑↑	Normal or ↑	↑↑

 

Step 6- What to do next

Once the pattern of LFT derangement has been established, it is crucial to determine the cause.

Common causes of acute hepatocellular injury include:

- Poisoning (paracetamol overdose)

- Infection (Hepatitis A and B)

- Liver ischaemia

 

Common causes of chronic hepatocellular injury include:

- Alcoholic fatty liver disease

- Non-alcoholic fatty liver disease

- Chronic infection (Hepatitis B or C)

- Primary biliary cirrhosis

- Less common causes of chronic hepatocellular injury include:

- alpha-1 antitrypsin deficiency

- Wilson’s disease

- Haemochromatosis