diagnosis

Last reviewed 01/2018

It is a diagnosis of exclusion - typically made after ruling out other causes of raised unconjugated bilirubin (1).

Diagnosis of Gilbert's syndrome can be based on when the person has:

• unconjugated hyperbilirubinaemia with normal plasma bile acids - an increase in unconjugated plasma bilirubin can be seen following:

• low energy diet for 24-48 hours, especially a reduction in lipids - but a similar magnitude of increase may be seen in hepatitis
• intravenous injection of nicotinic acid - normally rises to a maximum within 90 minutes; in Gilbert's disease, levels reach more than twice the basal level with a peak after 2 to 3 hours. The nicotinic acid causes a red cell haemolysis and thus a bilirubin load
• this is non specific and cannot be used to differentiate Gilbert’s syndrome form other causes of unconjugtaed hyperbilirubinemia (2)
• no overt or clinically recognised haemolysis
• normal liver function tests
• no systemic symptoms (3)
• a fall in bilirubin with phenobarbitone - a non-specific liver enzyme induction effect

There is no bilirubinuria; unlike haemolytic anaemia, urinary urobilinogen is not increased.

Liver biopsy is not indicated.

A heuristic for whether there should be further investigation has been stated as (1):

In an asymptomatic adult who presents with an increased bilirubin level that is:

• < 3 times the upper limit of normal with > 70% of bilirubin unconjugated and liver function tests are otherwise normal - the diagnosis is probably Gilbert's syndrome
  
  
  • interval retest in 1-3 months with proportion of indirect (unconjugated) bilirubin should be done
    
    
    • if the level of unconjugated bilirubin is non progressive, no further testing is needed
      
      
    • if unconjugated bilirubin levels are rising consider haemolysis and request serum haptoglobin, lactase dehydrogenase, full blood count with reticulocyte count (1)
      
      
• > 3 times the upper limit of normal with > 70% of bilirubin unconjugated and liver function tests are otherwise normal - consider haemolysis (1)

Reference:

• (1) Smellie WS, Ryder SD. Biochemical "liver function tests". BMJ. 2006;333(7566):481-3
• (2) Radu P, Atsmon J. Gilbert's syndrome--clinical and pharmacological implications. Isr Med Assoc J. 2001;3(8):593-8.
• (3) Mahdi AS, Elameer MS. Co-occurrence of Gibert’s syndrome and psychosis