Sunday, November 11, 2012

USES OF LIVER FUNCTION TEST


Differential diagnosis of Jaundice:

1.      Prehepatic jaundice:

This is caused by hemolytic conditions (sickle cell disease, shperocytosis, autoimmune). There is increased in unconjugated bilirubin, bound to albumin and thus absent in urine, hence the term ‘acholuric jaundice’. Since conjugation is normal, the level of urobilinogen in urine and faeces increases, because more bilirubin is conjugated. The Hb level is subnormal. Liver enzymes will be normal. Absence of urinary bilirubin. Presence of urinary and faecal urobilinogen and unconjugated hyperbilirubinemia. Presence of bilirubin in urine indicates presence of hepatic or biliary tract disease. It precedes hyperbilirubinaemia so provides early indication of liver damage.

2.      Hepatic (hepatocellular) jaundice:

This occurs due to primary damage to hepatocytes. There is both conjugated and unconjugated hyperbilirubinemia. Urinary level of bilirubin increases. Liver enzymes are abnormal. ALP increases along with γ-GT. ALT is elevated along with AST.

3.      Post hepatic (cholestatic or obstructive, regurgitation) jaundice

There is failure of biliary secretion. This failure may be at the level of hepatocytes, obstruction occurring anywhere between biliary canaliculi and the gut. There is conjugated hyperbilirubinemia. ALP and 5’-NT are elevated. There is lower AST/ALT ratio. Absence of urinary urobilin and faecal stercobilin thus stool is clay colored. Due to regurgitation bile salts appear in urine.

4.      The inherited hyperbilirubinaemias:

a. Unconjugated hyperbilirubinemia (Of the total bilirubin increased if increase in conjugated   bilirubin is <20% this is called unconjugated hyperbilirubinemia).

The crigler-najjar syndrome: 

There is complete absence of (type 1) or reduction (type 2) or UDP-glucuronyl transferase activity and is inherited as autosomal recessive trait. Due to failure of conjugation there is unconjugated hyperbilirubinemia in type 1. In type 2 both fraction are increased but higher is unconjugated. This bilirubin can cross BBB causing kernicterus. In type 1 there is high mortality but in type 2, survival is prolonged by giving phenobarbital (which induces enzyme synthesis) along with phototherapy.

Gilbert’s syndrome: 

It is common and characterized by recurrent mild jaundice, plasma bilirubin level being <100 µmol/L and only abnormality is standard liver test. There is increase in total bilirubin and the major fraction is unconjugated bilirubin. This syndrome is due to reduction in concentration of isoform (UGT-1A) of UDP-glucuronyl transferase.

b. Isolated Conjugated hyperbilirubinemia:

Dubin-Johnson syndrome: 

This is inherited as autosomal recessive manner and characterized by decreased biliary canalicular transport of conjugated bilirubin due to mutation in transport protein. Another characteristic defect here is the most of the urinary coproporphyrin is type I, whereas in unaffected subjects it is mainly type II.

Rotor’s syndrome: This is also an autosomal recessive characterized by moderate jaundice; there is mild elevation in conjugated bilirubin. The cause is unknown.

5.      Neonatal jaundice

This is called physiological jaundice and bilirubin seldom exceeds 100 µmol/L and is predominantly unconjugated, due to increased hemolysis, decreased hepatic uptake and conjugation. This unconjugated fat soluble bilirubin can cross the BBB and cause brain damage (Kernicterus). Prophylaxis is by phototherapy at 450 nm when bilirubin is very high >300 µmol/L.

Role of LFT in Assessing Prognosis:

Chronic liver disease:

Child-Turcotte-pugh (CTP) classification of severity of liver disease is,

Biochemical finding                    1                      2                         3
Ascitis                                      Absent             Slight               Moderate
Encephalopathy (grade)         none                1 and 2            3 and 4
Bilirubin (µmol/L)                     <25                  25-40               >40
Albumin (g/L)                           >35                  28-35               <28
PT                                              1-4                   4-6                   >6
(Seconds prolonged)

Mild (grade A) –scoring of 5 or 6 points
Moderate (Grade B) – 7-9 points
Severe (Grade C) – 10-15 points 
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