A 19 - year - old m an p

resenting with jaundice

 Mr John Adam
• is a 19 - year - old student who presents with
– a short history of abdominal discomfort and
jaundice.
– He has associated symptoms of fatigue, decreased
appetite andmyalgia.
• You have been asked to review him in the
jaundice clinic.
 What is the differential diagnosis
for his jaundice?
• Prehepatic jaundice (e.g. haemolysis).
• Hepatocellular jaundice (e.g. hepatitis).
• Posthepatic jaundice (e.g. obstruction of the
biliary tree).
 What additional questions would be
helpful in your routine history?
• How long has he had these symptoms?
An assessment of the chronology of his symptoms should be made to try
to determine whether this is an acute or chronic process.
In doing so it is important to recognise that liver disease can frequently be
asymptomatic for months or years prior to presentation; however, a history of
vague symptoms such as tiredness or anorexia might suggest a
chronic process.

•Has he had a similar episode before?

A history of becoming jaundiced with previous viral illnesses might suggest a diagnosis
of Gilbert ’ s syndrome.
Alternatively, it might represent a rarer cause of jaundice such as haemolytic anaemia
or benign, recurrent intrahepatic cholestasis (BRIC), an autosomally recessive disorder
characterised by intermittent attacks of cholestasis that
spontaneously resolve.
 What additional questions would be
helpful in your routine history?
• What are the colour of his stools and urine?
Dark urine and pale stools suggests an obstructive or cholestatic picture. The
presence of these changes does not differentiate between intrahepatic and
extrahepatic biliary obstruction, however, but they do differentiate from a
prehepatic cause of jaundice.

• What is the nature of his pain?

Pain of biliary origin (severe, right upper quadrant pain in a band) may raise
the suspicion of an obstructive picture secondary to gallstones.
Pain of acute hepatitis is usually not severe but
more of a dull ache over the liver.
 What additional questions would be
helpful in your routine history?
• Is there a history of travel?
Acute viral hepatitis may present with jaundice.
Hepatitis A and E are transmitted by the faecal – oral route and are frequently
acquired in countries where sanitation is poor (e.g. in Asia and Africa).
Hepatitis B is transmitted parenterally and has a high prevalence in areas such
as Asia and Africa.
Sexual contact or surgery or receipt of blood products in such a
country should be enquired about.

•Is there any family history?

There is a genetic component to some of the prehepatic causes of jaundice.
For example, glucose- 6- phosphate dehydrogenase (G6PD) defi ciency is an X
- linked recessive condition and haemolysis can be precipitated by
antimalarial medication.
 What additional questions would be
helpful in your routine history?
• Has he been in contact with anyone with a
similar illness?
Infection with hepatitis A and occasionally hepatitis E can result
in outbreaks in communities.

•Does he have any risk factors for transmissible

hepatitis?
A sexual history should be obtained as well as a history of intravenous drug use.
Enquiries should be made about receipt of blood products, surgery in
underdeveloped countries, tattoos and body piercing.
As some hepatitis viruses can have incubation periods of as long as 6 months it is
important to extend the history taking over that period.
 What additional questions would be
helpful in your routine history?
• What is his alcohol intake?
Alcohol is a common cause of jaundice and should always be
specifi cally enquired about.

• Has he taken any medication?

Prescribed and recreational drugs should be asked about.

Antibiotics and herbal remedies are often taken and forgotten about so
specifically ask about these.
Drugs can cause a hepatocellular or cholestatic hepatitis.
 Mr Adam describes
• no change in colour of his stools or urine.
• His abdominal discomfort is mild and left sided
but is constant.
• There has been no recent travel abroad,
• he denies
• any recreational drugs or recent medications and
he is teetotal.
• He is unaware of any family history of jaundice.
What clinical signs would you look for?
In addition to excluding signs of chronic liver disease the
following may be useful to look for in this case:
• Confirm the presence of jaundice by examining the sclera.
• Hepatosplenomegaly and lymphadenopathy may
imply an underlying haematological disorder.
• Tenderness in the right upper quadrant may suggest
gallstones.
• Kayser– Fleischer rings in the eyes are associated with
Wilson ’ s disease.
• On examination Mr Adam is jaundiced.
• He has mild splenomegaly and axillary
lymphadenopathy.
• No signs of chronic liver disease are seen.
• Blood tests reveal the following:
– Bilirubin 48 μmol/L ( normal value 0.1 to 1.2 mg/dL
(1.71 to 20.5 µmol/L)
– ALT 28 iU/L
– ALP 95 iU/L
– Albumin 36 g/L
– Hb 13.6 g/dL
– WBC 6.7 × 10 9 /L
– Plt 520 × 10 9 /L
 What a dditional i nvestigations
would be helpful?
• The liver function tests are all normal except for an isolated hyperbilirubinaemia. This is suggestive
of a prehepatic jaundice. The major differential diagnosis is an overproduction of bilirubin (e.g.
haemolysis) or disturbance of bilirubin conjugation.
The following investigations would be helpful:
• Conjugated/unconjugated bilirubin:
– An elevated uncon -jugated bilirubin (indirect) would confirm a prehepatic cause of
jaundice. In the absence of haemolysis this would suggest an inherited disorder of
conjugation such as Gilbert ’ s syndrome or Crigler – Najjar syndrome.

• Haemolysis screen: This includes a blood film for fragmented

• red blood cells; an absolute reticulocyte count; plasma levels of haptoglobin; and haemosiderin
detection in the urine.

• Viral serology: The absence of a transaminitis suggests that this is not a viral hepatitis. The
splenomegaly and lymphadenopathy imply this, however, could be due to a systemic viral
infection and serology for Epstein – Barr virus (EBV) and cytomegalovirus (CMV) would be useful.
 Further investigations
• an indirect bilirubin of 35 μ mol/L
• a direct bilirubin of 13 μ mol/L.
• The haemolysis screen isnegative.
• Serology shows the presence of high EBV IgM
titres suggestive of recent infection.
• The likely diagnosis is therefore that of Gilbert ’ s
syndrome (Box 1.1 ) with jaundice precipitated by
an intercurrent illness (EBV infection ).
 Gilbert ’ s syndrome
• Prevalence is approximately 5% in Western society
• It results from a genetic defect in UGT1A1 on chromosome 2 (autosomal
recessive) and results in decreased hepatic glucuronidation (by
approximately 30%)
• Fasting will increase bilirubin levels and this can be a useful diagnostic test
• Bilirubin levels are usually less than 100 μ mol/L
• Liver biopsy is not necessary and if performed is normal
• The condition is entirely benign and associated with a normal lifespan
• It is a related condition of the Crigler – Najjar syndrome.

Type 1 results in a complete absence of conjugating enzyme with severe

hyperbilirubinaemia, usually presenting in early life.

In type 2, the conjugating enzyme is reduced to less than 10%. The

bilirubinaemia in type 2 is usually higher than Gilbert ’ s syndrome but
molecular analysis can distinguish these two conditions
 What treatment and further follow
–up would you recommend?
The jaundice will improve and no specific treatment is
required.
Reassurance should be given to the patient.
It is also important to warn them that future episodes
may occur and be precipitated by illness or fasting.
Regular follow - up in a liver clinic is not required.

It would be extremely rare for EBV to produce a chronic

hepatitis although not uncommon for it to be
associated with a prolonged period of fatigue.
 CASE REVIEW
• A young man presented with jaundice and
isolated elevation in bilirubin.
• The absence of derangement in other liver
function tests and raised indirect bilirubin levels
was suggestive of a disorder in conjugation or
haemolysis.
• The negative haemolysis screen was helpful in
establishing the diagnosis of Gilbert ’ s syndrome
precipitated by an intercurrent illness (acute EBV
infection).
 KEY POINTS
• An isolated hyperbilirubinaemia in the absence of a
transaminitis suggests a prehepatic cause for the
jaundice
• A haemolysis screen and separation of bilirubin into
‘ direct ’ and ‘ indirect ’ components are important tests
for prehepatic jaundice
• The management of Gilbert ’ s syndrome is
conservative
• The long - term prognosis of Gilbert ’ s syndrome is
excellent; patients have a normal lifespan and require no
active intervention