http://www.bdf.org.uk/leaflets/gilbert.

html

W hat is it?
Gilbert's syndrome is a common, often inherited disorder that affects processing by the
liver of the greenish-brown pigments in bile (called bilirubin). The resulting abnormal
increase of bilirubin in the bloodstream can lead to yellowing of the skin (jaundice) but the
liver itself remains normal. It is more common in men than women and is named after a
French gastroenterologist.

W hat causes it?

About half the people affected inherit the condition which is probably due to decreased
activity of an enzyme in the liver.

W ho suffers?
Gilbert's syndrome affects about 5% of the population. It is usually detected by chance
often at a routine medical examination, in adolescence or early adult life.

W hat are the signs and symptoms?

Usually there are no symptoms but sufferers may experience mild jaundice, bouts of
abdominal pain, loss of appetite, fatigue and weakness after suffering an infection.
Repeated vomiting, missing meals, vigorous exercise or a feverish illness may also lead to
these symptoms.

W hat investigations and treatment are necessary?

Blood tests are usually carried out simply to make a diagnosis and to exclude liver disease.
No treatment is required.

W hy bother about it?

People with Gilbert's syndrome have a normal life expectancy. There is no hard evidence
that the disorder is associated with other more serious diseases.

So why bother about it? Suddenly turning yellow (becoming jaundiced) can be extremely
alarming in itself. However, more importantly, jaundice can be a sign of other more serious
infectious illnesses (such as hepatitis) which rightly cause concern to doctors and also to
sufferers and their families. Under these circumstances the urine usually become dark
brown, and urgent medical attention would be required.

Knowing about the diagnosis of the harmless Gilbert's syndrome, therefore, not only
provides reassurance to sufferer, family and close associates, but also to the family doctor
who would otherwise subject the yellow patient to a series of investigations out of concern
to exclude more serious illnesses. At the same time, alarm about the possible spread of
infection can also be dispelled.

W hat should we do?

For these reasons the British Digestive Foundation suggests that all those with Gilbert's
Syndrome carry with them at all times the message on this page - I am a Gilbert's
Syndrome Sufferer
Gilbertov sindrom-kronična benigna nekonjugirana hiperbilirubinemija. Nasljedni
poremećaj, četri puta češći kod muškaraca nego kod žena. U većine bolesnika radi se o
smanjenom prijenosu bilirubina u hepatocite, a u trećine je reducirana i glukuronil-
transferaza. Klinički se prezentira prolaznim žuticama (javljaju se npr. kod gladovanja,
uzimanja alkohola, umora).

http://www.medic8.com/healthguide/articles/gilbertsyn.html

GILBERT'S SYNDROME - a patient's guide

Dr Philip Wong - Gastroenterologist and Hepatologist

Gilbert's Syndrome

Gilbert's syndrome is a common inherited disorder that affects the processing by the liver
of the pigments in the bile called bilirubin. This results in an increase in the level of
bilirubin levels in the bloodstream and can lead to a yellowing of the skin and the eyes,
that is jaundice. The liver itself is otherwise normal and people with Gilbert's syndrome
have a normal life expectancy. It is common and not a dangerous condition in any way.

Enzyme Defect

Gilbert's syndrome is arguably the most common medical syndrome identified. In normal
people bilirubin is bound (conjugated) to specific protein(s) by a liver enzyme, called
bilirubin-uridine glucuronosyltransferase (bilirubin-UGT), which allows it to be excreted in
the bile. It has long been recognised that bilirubin-UGT activity measured in liver biopsies
of individuals with Gilbert's syndrome is almost invariably reduced, suggesting that
reduced enzyme activity is the source of the impairment in bilirubin metabolism. Thus in
Gilbert's syndrome bilirubin is less efficiently excreted into the bile leading to elevated
levels of unconjugated bilirubin in the bloodstream.

Clinical and laboratory findings

Gilbert's syndrome is most often recognised in the second or third decade of life and is
rarely diagnosed before puberty. The diagnosis is made most often following routine
screening blood tests or when fasting associated with surgery or intercurrent illness
unmasks the hyperbilirubinemia. Gilbert's syndrome affects 3 to 7% of the population,
with males predominating over females by a ratio of 2-7:1.

The normal bilirubin level in the blood is less than 20 umol/L while in Gilbert's syndrome
the bilirubin level is usually mildly raised. In most cases is less than 50 umol/L and is
always less than 100 umol/L. There is considerable daily and seasonal fluctuation. The
bilirubin may be normal on occasion in up to one-third of patients.

Because the liver is otherwise normal in individuals with Gilbert's syndrome, physical
examination is normal apart from the occasional presence of jaundice. At least 30% of
patients with Gilbert's syndrome are asymptomatic, apart from the presence of mild
jaundice, and are unaware of the abnormality until it is detected by incidental laboratory
examination or in the course of family studies. Some people may experience a variety of
nonspecific and varied symptoms, including vague abdominal discomfort, fatigue, or
malaise In general, these symptoms do not correlate with the plasma bilirubin level and
are more likely related to anxiety rather than to the underlying disorder in metabolism.
In a third group of patients, hyperbilirubinemia may be unmasked during fasting, which
usually produces an increase in the plasma unconjugated bilirubin level. Thus, sub clinical
individuals may first be detected in association with caloric withdrawal due to an
intercurrent febrile illness, "morning sickness" of pregnancy or postoperatively.

Diagnosis and Treatment

The diagnosis of Gilbert's syndrome is suggested by the clinical finding of mild chronic
unconjugated hyperbilirubinemia. A family history should be sought and clinical evidence
of other liver or blood disorders, including haemolysis (abnormal breakdown of red cells)
excluded. Further confirmation of the diagnosis may be achieved by determining the
effect of fasting or intravenous nicotinic acid administration on the blood bilirubin
concentration. Either manipulation generally results in a two- to threefold rise in plasma
bilirubin level, even if the initial bilirubin concentrations are normal. However, not all
patients with Gilbert's syndrome respond to these tests, which appear less sensitive and
specific for females than males. Other diagnostic manoeuvres that have been advocated
are measurement of the effect of phenobarbital on plasma bilirubin concentration, and
the administration of a tracer dose of radiolabeled bilirubin for estimation of the
percentage of the dose remaining in the plasma after 4 hours.

Given the above considerations, a presumptive diagnosis of Gilbert's syndrome can be

made in an essentially asymptomatic individual if he /she has (1) unconjugated
hyperbilirubinemia on several occasions; (2) normal results of a complete blood cell
count, blood smear, and reticulocyte count; and (3) normal liver enzyme tests (see
article on liver function tests) and (4) other disease processes have been excluded. If no
further laboratory abnormalities develop on two or three follow-up tests during the next
12 to 18 months, then the presumptive diagnosis becomes definitive. It is conceivable
that genetic testing may play a role in the diagnosis of this condition in the future.

Once the diagnosis is established, the most important aspect of management is to

reassure the patient with regard to the benign and inconsequential nature of the disorder
and the excellent prognosis and to prevent further unnecessary investigations.

http://www.emedicine.com/med/topic870.htm

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Gilbert Syndrome
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Last Updated: January 21, 2005
Get CME/CE for article
Synonyms and related keywords: constitutional hepatic dysfunction, constitutional
hyperbilirubinemia, familial nonhemolytic jaundice, hereditary nonhemolytic bilirubinemia,
low-grade chronic hyperbilirubinemia
AUTHOR INFORMATION Section 1 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

Author: Sandeep Mukherjee, MD, Assistant Professor, Department of Internal Medicine,

Section of Gastroenterology and Hepatology, University of Nebraska Medical Center
Sandeep Mukherjee, MD, is a member of the following medical societies: American College
of Gastroenterology, American Society for Gastrointestinal Endoscopy, American Society of
Transplantation, and Royal College of Physicians and Surgeons of Canada
Editor(s): Manoop S Bhutani, MD, FACG, FACP, Professor, Department of Medicine,
Division of Gastroenterology, Director, Center for Endoscopic Ultrasound, Co-Director,
Center for Endoscopic Research, Training and Innovation, University of Texas Medical
Branch at Galveston; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor,
eMedicine; Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of
Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical
Group; Alex J Mechaber, MD, FACP, Associate Professor, Department of Internal
Medicine, Division of General Internal Medicine, University of Miami School of Medicine;
and Julian Katz, MD, Professor, Department of Internal Medicine, Division of
Gastroenterology, Drexel University College of Medicine

Disclosure

INTRODUCTION Section 2 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

Background: Augustine Gilbert and Pierre Lereboullet first described Gilbert syndrome, the
most common inherited cause of unconjugated hyperbilirubinemia, in 1901. This autosomal
recessive condition is characterized by intermittent jaundice in the absence of hemolysis or
underlying liver disease. The hyperbilirubinemia is mild and, by definition, less than 6 mg/dL.
However, most patients exhibit levels of less than 3 mg/dL. Considerable daily and seasonal
variations are observed, and bilirubin levels occasionally may be normal in as many as one
third of patients.

Gilbert syndrome may be precipitated by dehydration, fasting, menstrual periods, or stress,

such as an intercurrent illness or vigorous exercise. Patients may report vague abdominal
discomfort and general fatigue for which no cause is found. These episodes resolve
spontaneously, and no treatment is required except supportive care.

Pathophysiology: Unconjugated hyperbilirubinemia in Gilbert syndrome has long been

recognized as due to underactivity of the conjugating enzyme system bilirubin-uridine
diphosphate glucuronyl transferase (bilirubin-UGT). Bilirubin-UGT is responsible for
conjugating bilirubin into bilirubin monoglucuronides and diglucuronides and is located
primarily in the endoplasmic reticulum of hepatocytes. Bilirubin-UGT is one of several UGT
enzyme isoforms responsible for the conjugation of a wide array of substrates that include
carcinogens, drugs, hormones, and neurotransmitters.

Knowledge of these enzymes has been enhanced greatly by characterization of the UGT1
gene locus in humans. The gene that expresses bilirubin-UGT has a complex structure and is
located on chromosome 2. There are 5 exons, of which exons 2-5 at the 3' end are constant
components of all isoforms of UGT, coding for the UDP-glucuronic acid–binding site. Exon 1
encodes for a unique region within each UGT and confers substrate specificity. However,
multiple exon 1s (at least 13) exist, and, to complete the gene, one of these exons must be
recruited. Exons 1a and 1d encode the variable region for bilirubin UGT1*1 (also known as
UGT1A1) and UGT1*2, respectively, with UGT1*1 responsible for virtually all bilirubin
conjugation and UGT1*2 playing little, if any, role. Expression of UGT1*1 depends on a
promoter region in a 5' position relative to each exon 1 that contains a TATAA box. Impaired
bilirubin glucuronidation therefore may result from mutations in exon 1a, its promoter, or the
common exons.

A breakthrough in understanding the genetic basis of Gilbert syndrome was achieved in 1995,
when abnormalities in the TATAA region of the promoter were identified. The addition of 2
extra bases (TA) to the TATAA region interferes with binding of the transcription factor IID
and results in reduced expression of bilirubin-UGT1 (30% of normal). In the homozygous
state, diminished bilirubin glucuronidation is observed, with bile containing an excess of
bilirubin monoglucuronide over diglucuronide. Additional mutations have since been
identified. For example, some healthy Asian patients with Gilbert syndrome do not have
mutations at the promoter level but are heterozygotes for missense mutations (Gly71Arg,
Tyr486Asp, Pro364Leu) in the coding region. These individuals also have significantly higher
bilirubin levels than those with the wild-type allele.

Presently, whether reduced bilirubin-UGT activity results from a reduced number of enzyme
molecules or from a qualitative enzyme defect is unknown. To compound this further, other
factors, such as occult hemolysis or hepatic transport abnormalities, may be involved in the
clinical expression of Gilbert syndrome. For example, many individuals homozygous for the
TATAA defect do not demonstrate unconjugated hyperbilirubinemia, and patients with
reduced levels of bilirubin-UGT, as observed in some granulomatous liver diseases, do not
develop hyperbilirubinemia.

Because of the high frequency of mutations in the Gilbert promoter, heterozygous carriers of
Crigler-Najjar syndromes types 1 and 2 can also carry the elongated Gilbert TATAA
sequence on their normal allele. Such combined defects can lead to severe hyperbilirubinemia
and also help explain the finding of intermediate levels of hyperbilirubinemia in family
members of patients with Crigler-Najjar syndrome. Gilbert syndrome can also frequently
coexist with the conditions associated with unconjugated hyperbilirubinemia, such as
thalassemia and glucose-6-phosphate deficiency

Frequency:

 In the US: The rate of Gilbert syndrome in the United States is 3-7% of the
population.

 Internationally: The worldwide prevalence of Gilbert syndrome varies considerably

depending on which diagnostic criteria are used, such as number of bilirubin
determinations, method of analysis, bilirubin levels used for diagnosis, and whether
the patient was fasting. This may be complicated further by recent molecular genetic
studies of polymorphisms in the TATAA promoter region, which affects as many as
36% of Africans but only 3% of Asians. The clinical phenotype may not be as
apparent as the determined genotype because of environmental influences, such as
alcohol-induced bilirubin glucuronidation, which can reduce bilirubin levels.
Mortality/Morbidity: Gilbert syndrome is a benign condition with no associated morbidity
or mortality.

Race: Gilbert syndrome is not restricted to any ethnic group and occurs in persons of all
races.

Sex: Population studies show that Gilbert syndrome occurs predominately in men, with a
male-to-female ratio ranging from 2-7:1.

Age: Gilbert syndrome is usually diagnosed around puberty, possibly because of the
inhibition of bilirubin glucuronidation by endogenous steroid hormones. In older persons, the
diagnosis is usually made when unconjugated hyperbilirubinemia is noted on routine blood
test results or unmasked by an intercurrent illness or stress.

CLINICAL Section 3 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

History: At least 30% of patients are asymptomatic, although nonspecific symptoms such as
abdominal cramps, fatigue, and malaise are common. Abdominal symptoms in these patients
are a poorly defined entity and may be secondary to underlying anxiety. However, not all
patients with Gilbert syndrome and abdominal symptoms are anxious; nevertheless, they
appear to have organic-type discomfort that is hard to characterize and frequently eludes
diagnosis. No relationship exists between these abdominal symptoms and plasma bilirubin
levels. Abdominal symptoms apparently may be multifactorial, with underlying anxiety
probably playing an important role.

Physical: Mild jaundice is present intermittently in some individuals, but no other abnormal
physical examination findings are evident. Infants homozygous for Gilbert syndrome may
have a greater increase in neonatal jaundice when breastfed or when other disorders of heme
metabolism are coinherited.

Causes:

 Dehydration

 Fasting: This produces an increase in the plasma unconjugated bilirubin level.

 Intercurrent illness, such as a viral infection

 Menstrual periods

 Stress, such as trauma and overexertion

DIFFERENTIALS Section 4 of 9
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Biliary Disease

Other Problems to be Considered:

Hemolysis
Hematoma
Acute and chronic liver disease
Primary hyperbilirubinemia from ineffective erythropoiesis
Glucuronyl transferase deficiency
Infections
Cardiac disease (eg, congestive heart failure, prosthetic heart valves)
Rhabdomyolysis
High-altitude living
Medications (eg, probenecid, rifamycin, other antibiotics)
Thyrotoxicosis

As can be inferred from the above list, Gilbert syndrome has a broad differential diagnosis
because causes of unconjugated hyperbilirubinemia must be considered.

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WORKUP Section 5 of 9
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Lab Studies:

 CBC count (including reticulocyte count and blood smear): This is a useful screening
test to exclude hemolysis. Rarely, red blood cell abnormalities resembling variegate
porphyria have been described in persons with Gilbert syndrome, possibly due to the
increased hepatocellular bilirubin concentration.

 Lactate dehydrogenase: Levels are elevated in persons with hemolysis but are normal
in those with Gilbert syndrome.
  Liver function tests: With the exception of unconjugated hyperbilirubinemia, standard
liver function test results are normal. However, a familial increase in serum alkaline
phosphatase levels has been reported in persons with Gilbert syndrome.

Imaging Studies:

 Imaging studies are not required to confirm a diagnosis of Gilbert syndrome.

Other Tests:

 Additional tests are rarely required because a diagnosis of Gilbert syndrome can be
made in the presence of (1) unconjugated hyperbilirubinemia noted on several
occasions; (2) normal results from CBC count, reticulocyte count, and blood smear;
(3) normal liver function test results; and (4) an absence of other disease processes.

 The following investigations are occasionally performed to confirm a diagnosis of

Gilbert syndrome. Those of historical interest, as well as the newer molecular genetic
techniques, are included. They are described to introduce the clinician to the broad
diagnostic armamentarium available for diagnosing Gilbert syndrome. Recourse to
these specialized tests should be rare and is usually difficult to justify in clinical
practice because the diagnosis of Gilbert syndrome is usually straightforward.

o Fasting: This usually results in a 2- to 3-fold rise in the plasma unconjugated

bilirubin level within 48 hours of a fast that returns to normal levels within 24
hours of resuming a normal diet. Although unconjugated bilirubin levels also
rise with fasting in patients with hemolysis or liver disease, the magnitude of
the rise is less than that observed with Gilbert syndrome. A similar rise in
plasma bilirubin is also observed with normocaloric diets deficient in lipids
and reverses promptly with lipid replacement. The precise mechanism of
fasting and dietary-induced hyperbilirubinemia remains unclear. The fasting
test remains of historic interest and has limited usefulness in the diagnosis of
Gilbert syndrome.

o Nicotinic acid: Intravenous administration of 50 mg of nicotinic acid results in

a 2- to 3-fold rise in plasma unconjugated hyperbilirubinemia within 3 hours.
The mechanisms are multifactorial and probably related to (1) elevated
osmotic fragility of red blood cells, (2) increase in splenic production of
bilirubin, (3) transient inhibition of hepatic bilirubin-UGT activity, and (4)
increased splenic heme oxygenase activity. Although a similar but less
impressive increase is observed in healthy individuals and those with
hemolysis or liver disease, the nicotinic test, similar to fasting, does not clearly
distinguish patients with Gilbert syndrome from those who are healthy or who
have other disease processes.

o Phenobarbital: Phenobarbital and other enzyme inducers of the bilirubin-UGT

system will normalize plasma bilirubin in patients with Gilbert syndrome. This
is predominantly due to accelerated bilirubin clearance from enzyme induction
but is also due to reduced bilirubin turnover. Steroids can also reduce plasma
bilirubin levels in Gilbert syndrome by increasing hepatic uptake and storage
of bilirubin.
 o Radioactive-labeled chromium: This is used to measure red blood cell survival.
As many as 60% of patients with Gilbert syndrome have a mild and fully
compensated state of hemolysis together with increased hepatic heme
production. As a result, hyperbilirubinemia may be due to reduced bilirubin
clearance and increased production, the latter from increased erythroid or
hepatic heme turnover.

o Thin-layer chromatography: This test is diagnostic for Gilbert syndrome when

it shows a significantly higher proportion of unconjugated bilirubin compared
with individuals with chronic hemolysis or liver disease or those who are
healthy. If confirmation of the diagnosis is truly essential, chromatographic
determination is of potential use. This shows an increased ratio of bilirubin
monoglucuronide to diglucuronide, reflecting reduced bilirubin-UGT activity.

o Drug clearance: Approximately 30% of patients have impaired clearance of

bromosulfophthalein, indocyanine green, and free fatty acid, suggesting an
abnormality in hepatic uptake, transport, or both. The metabolic clearance of
tolbutamide is also reduced in persons with Gilbert syndrome, but, because it
does not undergo glucuronidation, hepatic uptake appears to be defective.
Plasma clearance of most drugs that undergo glucuronidation (eg,
benzodiazepines) is unaffected. However, with regard to acetaminophen,
patients with Gilbert syndrome are a heterogeneous group, with some
demonstrating normal metabolism and others exhibiting marked reduction in
glucuronidation and an increase in oxidation. These changes could mean that
people in this subgroup could be more susceptible to liver injury after an
acetaminophen overdose, although no such adverse events have been reported.

o Polymerase chain reaction: Polymerase chain reaction is a novel and rapid

method of identifying genetic polymorphisms in the TATA box of the UGT1*1
gene using fluorescence resonance energy transfer.

Procedures:

 Liver biopsies are not performed routinely and are rarely necessary.

Histologic Findings: The liver is normal histologically, except for occasional accumulation
of a lipofuscinlike pigment around the terminal hepatic venules.
TREATMENT Section 6 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

Medical Care: The most important aspect of treatment once the diagnosis is established is
reassurance. Patients with Gilbert syndrome should be informed of its benign nature and that
hyperbilirubinemia is not associated with increased morbidity. It has an excellent prognosis
and is associated with normal life expectancy, which must be made perfectly clear to the
patient.

Diet: Diet is normal.

Activity: No activity restrictions are necessary.

 FOLLOW-UP Section 7 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

Further Inpatient Care:

 Inpatient care is not required.

In/Out Patient Meds:

 Various medications have been used experimentally to reduce the hyperbilirubinemia

of Gilbert syndrome. For example, phenobarbital and glutethimide activate hepatic
bilirubin-UGT activity, while tin-protoporphyrin inhibits heme oxygenase to reduce
bilirubin levels.

 In light of the benign and inconsequential nature of this condition, the use of
medications in patients with Gilbert syndrome is unjustified in clinical practice.

Deterrence/Prevention:

 Avoid known risk factors for precipitating hyperbilirubinemia (eg, dehydration,

fasting).

Prognosis:

 Gilbert syndrome is a common and benign condition. The bilirubin disposition may be
regarded as falling within the range of normal biological variation. It has no
deleterious associations and an excellent prognosis, and those who have it can lead a
normal lifestyle.

Patient Education:

 Patients should be warned that they might develop jaundice if they miss meals,
become dehydrated, develop an infection (eg, viral infection), or undergo stress.

MISCELLANEOUS Section 8 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

Medical/Legal Pitfalls:

 Gilbert syndrome can be diagnosed by a thorough history and physical examination

and confirmed by standard blood tests. Repeated investigations and invasive
procedures are not usually justified for establishing a diagnosis. Studies can be
conducted within the realms of an institutional review board–approved study.

 The clinical relevance of pharmacogenetics in Gilbert syndrome is yet to be

determined. Although impaired glucuronidation and excretion of certain drugs has
been reported, this has not resulted in any adverse clinical events, and the risk
probably remains more theoretical than real.
  Irinotecan toxicity in Gilbert syndrome is of some concern. Affected patients have
reduced inactivation of the active topoisomerase inhibitor 7-ethyl-10-
hydroxycampothecin (SN-38) caused by a mutation in the UDT-1*1 gene promoter.
Glucuronidation rates of the active metabolite SN-38 are significantly lower in people
who are homozygous and heterozygous for the TA-TATAA variant allele compared
with the wild-type genotype (TATAA). In Gunn rats (an animal model of Crigler-
Najjar syndrome) and in people with Gilbert or Crigler-Najjar syndrome, reduced
glucuronidation of SN-38 leads to SN-38 toxicity and causes symptoms such as
diarrhea. Preliminary results from clinical trials suggest that screening cancer patients
for the UGT1*1 promoter polymorphism may reduce the prevalence of irinotecan
toxicity, and, until this evidence is available, caution is warranted before prescribing
irinotecan in this subset of patients.

BIBLIOGRAPHY Section 9 of 9
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Miscellaneous Bibliography

 Anderson KE, Simionatta CS, Drummond GS, Kappas A: Disposition of tin-

protoporphyrin and suppression of hyperbilirubinemia in humans. Clin Pharmacol
Ther 1986; May;39(5): 510-20[Medline].
 Aono S, Adachi Y, Uyama E, et al: Analysis of genes for bilirubin UDP-
glucuronosyltransferase in Gilbert's syndrome. Lancet 1995 Apr 15; 345(8955): 958-
9[Medline].
 Arias IM, London IM: Bilirubin glucuronide formation in vitro; demonstration of a
defect in Gilbert's disease. Science 1957 Sep 20; 126(3273): 563-4[Medline].
 Bancroft JD, Kreamer B, Gourley GR: Gilbert syndrome accelerates development of
neonatal jaundice. J Pediatr 1998 Apr; 132(4): 656-60[Medline].
 Beutler E, Gelbart T, Miller W: Severe jaundice in a patient with a previously
undescribed glucose-6-phosphate dehydrogenase (G6PD) mutation and Gilbert
syndrome. Blood Cells Mol Dis 2002 Mar-Apr; 28(2): 104-7[Medline].
 Black M, Sherlock S: Treatment of Gilbert's syndrome with phenobarbitone. Lancet
1970 Jun 27; 1(7661): 1359-61[Medline].
 Borlak J, Thum T, Landt O, et al: Molecular diagnosis of a familial nonhemolytic
hyperbilirubinemia (Gilbert's syndrome) in healthy subjects. Hepatology 2000 Oct;
32(4 Pt 1): 792-5[Medline].
 Bosma PJ, Chowdhury JR, Bakker C, et al: The genetic basis of the reduced
expression of bilirubin UDP- glucuronosyltransferase 1 in Gilbert's syndrome. N Engl
J Med 1995 Nov 2; 333(18): 1171-5[Medline].
 Burchell B, Hume R: Molecular genetic basis of Gilbert's syndrome. J Gastroenterol
Hepatol 1999 Oct; 14(10): 960-6[Medline].
 Chalasani N, Chowdhury NR, Chowdhury JR, Boyer TD: Kernicterus in an adult who
is heterozygous for Crigler-Najjar syndrome and homozygous for Gilbert-type genetic
defect. Gastroenterology 1997 Jun; 112(6): 2099-103[Medline].
 Datta DV: Estimation of hepatic bilirubin-UDP-glucuronyl-transferase in patients with
non-cirrhotic portal fibrosis and liver disease: significance and limitations . Dig Dis
1975; 20: 961.
 Esteban A, Perez-Mateo M: Heterogeneity of paracetamol metabolism in Gilbert's
syndrome. Eur J Drug Metab Pharmacokinet 1999 Jan-Mar; 24(1): 9-13[Medline].
 Fang JL, Lazarus P: Correlation between the UDP-glucuronosyltransferase (UGT1A1)
TATAA box polymorphism and carcinogen detoxification phenotype: significantly
decreased glucuronidating activity against benzo(a)pyrene-7,8-dihydrodiol(-) in liver
 microsomes from subjects with. Cancer Epidemiol Biomarkers Prev 2004 Jan; 13(1):
102-9[Medline].
 Hall D, Ybazeta G, Destro-Bisol G, et al: Variability at the uridine diphosphate
glucuronosyltransferase 1A1 promoter in human populations and primates.
Pharmacogenetics 1999 Oct; 9(5): 591-9[Medline].
 Huang CS, Luo GA, Huang ML, et al: Variations of the bilirubin uridine-
diphosphoglucuronosyl transferase 1A1 gene in healthy Taiwanese. Pharmacogenetics
2000 Aug; 10(6): 539-44[Medline].
 Innocenti F, Iyer L, Ratain MJ: Pharmacogenetics: a tool for individualizing
antineoplastic therapy. Clin Pharmacokinet 2000 Nov; 39(5): 315-25[Medline].
 Kalotychou V, Antonatou K, Tzanetea R, et al: Analysis of the A(TA)(n)TAA
configuration in the promoter region of the UGT1 A1 gene in Greek patients with
thalassemia intermedia and sickle cell disease. Blood Cells Mol Dis 2003 Jul-Aug;
31(1): 38-42[Medline].
 Lieverse AG, van Essen GG, Beukeveld GJ, et al: Familial increased serum intestinal
alkaline phosphatase: a new variant associated with Gilbert's syndrome. J Clin Pathol
1990 Feb; 43(2): 125-8[Medline].
 Maruo Y, D Addario C, Mori A, et al: Two linked polymorphic mutations
(A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome.
Hum Genet 2004 Nov; 115(6): 525-6[Medline].
 McColl KE, Thompson GG, el Omar E, et al: Porphyrin metabolism and haem
biosynthesis in Gilbert's syndrome. Gut 1987 Feb; 28(2): 125-30[Medline].
 Metreau JM, Yvart J, Dhumeaux D, Berthelot P: Role of bilirubin overproduction in
revealing Gilbert's syndrome: is dyserythropoiesis an important factor? Gut 1978 Sep;
19(9): 838-43[Medline].
 Ohkubo H, Okuda K, Iida S: Effects of corticosteroids on bilirubin metabolism in
patients with Gilbert's syndrome. Hepatology 1981 Mar-Apr; 1(2): 168-72[Medline].
 Raijmakers MT, Jansen PL, Steegers EA, Peters WH: Association of human liver
bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter
region of the UGT1A1 gene. J Hepatol 2000 Sep; 33(3): 348-51[Medline].
 Rauchschwalbe SK, Zühlsdorf MT, Wensing G, Kuhlmann J: Glucuronidation of
acetaminophen is independent of UGT1A1 promotor genotype. Int J Clin Pharmacol
Ther 2004 Feb; 42(2): 73-7[Medline].
 Ritter JK, Chen F, Sheen YY, et al: A novel complex locus UGT1 encodes human
bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical
carboxyl termini. J Biol Chem 1992 Feb 15; 267(5): 3257-61[Medline].
 Rollinghoff W, Paumgartner G, Preisig R: Nicotinic acid test in the diagnosis of
Gilbert's syndrome: correlation with bilirubin clearance. Gut 1981 Aug; 22(8): 663-
8[Medline].
 Sieg A, Stiehl A, Raedsch R, et al: Gilbert's syndrome: diagnosis by typical serum
bilirubin pattern. Clin Chim Acta 1986 Jan 15; 154(1): 41-7[Medline].
 Skarke C, Grösch S, Geisslinger G, Lotsch J: Single-step identification of all length
polymorphisms in the UGT1A1 gene promoter. Int J Clin Pharmacol Ther 2004 Mar;
42(3): 133-8[Medline].
 Svahn J, Lanciotti M, Dufour C, et al: Gilbert syndrome as differential diagnosis of
hyperbilirubinemia in acquired aplastic anemia. Pediatr Blood Cancer 2005 Feb;
44(2): 197-8[Medline].
 Tzetis M, Kanavakis E, Tsezou A, et al: Gilbert syndrome associated with beta-
thalassemia. Pediatr Hematol Oncol 2001 Dec; 18(8): 477-84[Medline].
  Whitmer DI, Gollan JL: Mechanisms and significance of fasting and dietary
hyperbilirubinemia. Semin Liver Dis 1983 Feb; 3(1): 42-51[Medline].

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Hyperbilirubinemia, Conjugated
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Last Updated: December 1, 2005
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Synonyms and related keywords: icterus, jaundice, bilirubin accumulation, bilirubin
formation, tetrapyrrole, hemoglobin, unconjugated bilirubin, conjugated bilirubin, conjugated
hyperbilirubinemia, liver disease, biliary disease
AUTHOR INFORMATION Section 1 of 8
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Bibliography

Author: Richard A Weisiger, MD, Director, GI and Liver Faculty Practice, Professor,
Department of Internal Medicine, University of California San Francisco
Richard A Weisiger, MD, is a member of the following medical societies: American
Association for the Study of Liver Diseases, American Gastroenterological Association, and
American Society for Clinical Investigation Central
Editor(s): Vivek Gumaste, MD, Chief, Clinical Associate Professor, Department of Internal
Medicine, Division of Gastroenterology, Elmhurst Hospital Center, Mount Sinai School of
Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Oscar
S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of
California at San Diego; Consulting Staff, Mecklenburg Medical Group; Alex J Mechaber,
MD, FACP, Associate Professor, Department of Internal Medicine, Division of General
Internal Medicine, University of Miami School of Medicine; and Julian Katz, MD, Clinical
Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department
of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of
Pennsylvania

Disclosure

INTRODUCTION Section 2 of 8
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Bibliography

Background: Bilirubin is a tetrapyrrole created by the normal breakdown of heme. Most

bilirubin is produced during the breakdown of hemoglobin and other hemoproteins.
Accumulation of bilirubin or its conjugates in body tissues produces jaundice (ie, icterus),
which is characterized by high plasma bilirubin levels and deposition of yellow bilirubin
pigments in skin, sclerae, mucous membranes, and other less visible tissues.

Because bilirubin is highly insoluble in water, it must be converted into a soluble conjugate
prior to elimination from the body. In the liver, uridine diphosphate (UDP)-glucuronyl
transferase converts bilirubin to a mixture of monoglucuronides and diglucuronides, referred
to as conjugated bilirubin, which is then secreted into the bile by an ATP-dependent
transporter. This process is highly efficient under normal conditions, so plasma unconjugated
bilirubin concentrations remain low.

A large number of disease states lead to bilirubin accumulation in plasma. Diseases that
increase the rate of bilirubin formation, such as hemolysis, or diseases that reduce the rate of
bilirubin conjugation, such as Gilbert syndrome, produce unconjugated hyperbilirubinemia.

Diseases that reduce the rate of secretion of conjugated bilirubin into the bile or the flow of
bile into the intestine produce a mixed or predominantly conjugated hyperbilirubinemia due to
reflux of conjugates back into the plasma. Elevated conjugated bilirubin levels usually
indicate hepatobiliary disease.

Laboratory assays for bilirubin typically involve its cleavage in the presence of diazotized
sulfanilic acid to generate a colored azodipyrrole that can be assayed spectrophotometrically.
Due to its limited aqueous solubility, unconjugated bilirubin reacts slowly in the absence of an
accelerator, such as ethanol, while conjugated bilirubin reacts rapidly. Total bilirubin is
measured in the presence of an accelerator, while directly reacting bilirubin is measured
without an accelerator. Indirectly reacting bilirubin is calculated by subtracting the directly
reacting bilirubin score from the total bilirubin score. Although the directly reacting bilirubin
concentration approximates the conjugated bilirubin concentration in most cases, the two
terms do not mean the same thing. Similarly, indirect bilirubin is not the same as
unconjugated bilirubin.

The kidneys do not filter unconjugated bilirubin due to its avid binding to albumin. For this
reason, the presence of bilirubin in the urine indicates the presence of conjugated
hyperbilirubinemia.

Normal serum values of total bilirubin typically are 0.2-1 mg/dL (3.4-17.1 mol/L), of which
no more than 0.2 mg/dL (3.4 mol/L) are directly reacting.

Pathophysiology: Conjugated hyperbilirubinemia results from reduced secretion of

conjugated bilirubin into the bile, such as occurs in patients with hepatitis, or it results from
impaired flow of bile into the intestine, such as occurs in patients with biliary obstruction.
Bile formation is very sensitive to a variety of hepatic insults, including high levels of
inflammatory cytokines such as may occur in patients with septic shock.

High levels of conjugated bilirubin may secondarily elevate the level of unconjugated
bilirubin. Although the mechanism of this effect is not fully defined, one likely cause is
reduced hepatic clearance of unconjugated bilirubin resulting from competition with
conjugated bilirubin for uptake or excretion.

Frequency:
  In the US: Conjugated hyperbilirubinemia is a common abnormality among patients
with notable liver or biliary disease. It also may be observed in patients with systemic
illnesses such as sepsis and cardiogenic shock. The frequencies of the liver and biliary
diseases that cause conjugated hyperbilirubinemia are described for each specific
disease.

 Internationally: In certain lesser-developed countries, parasitic diseases, such as

clonorchiasis and ascariasis, commonly produce biliary obstruction. Hemolytic
diseases, such as malaria, may predispose patients to biliary obstruction through the
formation of pigment gallstones.

Mortality/Morbidity:

 Unlike unconjugated bilirubin, conjugated bilirubin does not bind significantly to

neural tissue and does not lead to kernicterus or other forms of toxicity.

 The morbidity and mortality associated with conjugated hyperbilirubinemia result

from the underlying disease process.

 In certain disease states, such as alcoholic hepatitis or primary biliary cirrhosis,

bilirubin levels correlate strongly with, but do not contribute to, short-term mortality.

Race: Racial differences reflect those for the specific disease states causing the condition.

Sex: Sex differences reflect those for the specific disease states causing the condition.

Age: The age distribution reflects the age distribution of the underlying disease states and
ranges from the first month of life, as in cases of biliary atresia; through midlife, as in cases of
viral hepatitis or primary biliary cirrhosis; to senescence, as in cases of biliary stones and in
malignancies.

CLINICAL Section 3 of 8
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History: Evaluation always starts with obtaining a full history.

 Potential toxins (eg, drugs), environmental chemicals (eg, solvents), or wild

mushrooms must be carefully excluded. Failure to diagnose toxic hepatitis promptly
may result in hepatic failure and death.

 Risk factors for viral hepatitis should be elicited. Possible risk factors include the
following:

o Transfusion
 o Intravenous (IV) drug use

o Multiple sexual partners

o Exposure to a person who is icteric

 Colicky abdominal pain or fever suggests gallstone disease.

 Weight loss or constitutional systems suggests malignancy or chronic infection.

 Recent anesthesia using halothane suggests halothane hepatitis.

 A history of intense pruritus suggests cholestatic disease resulting from biliary

obstruction or intrahepatic cholestasis.

 A family history of jaundice suggests inborn errors of bilirubin metabolism.

 In patients with severe intercurrent illnesses, consider sepsis, hepatic ischemia, and
opportunistic infections.

 Severe right heart failure or tricuspid insufficiency with hepatomegaly suggests

hepatic congestion.

 Patients on parenteral nutrition may experience cholestasis that sometimes improves

with the addition of lipid infusions.

 Patients with AIDS may experience biliary obstruction from opportunistic infection
(eg, AIDS cholangiopathy).

 Patients with chronic liver disease may experience transient elevation of their bilirubin
levels following blood transfusion, which results because of a more rapid turnover of
the infused cells.

 In patients younger than 20-25 years, a history of a recent flulike syndrome treated
with aspirin raises the possibility of Reye syndrome.

 Pregnancy suggests benign recurrent cholestasis or, in late pregnancy, acute fatty liver
of pregnancy.

 A categorical listing of the most common diseases that produce conjugated

hyperbilirubinemia is presented in the Table.

Differential Diagnosis of Conjugated Hyperbilirubinemia

I. Acute or Chronic Hepatocellular II. Diseases that Prevent Flow of Bile into the
Dysfunction Intestine
A. Infection A. Damage to Intrahepatic Bile Ducts or Portal
Tracts

Viral hepatitis A-E Primary biliary cirrhosis

Cytomegalovirus (CMV) hepatitis Graft-versus-host disease

Epstein-Barr virus hepatitis Veno-occlusive disease

Sepsis Sclerosing cholangitis

B. Inflammation Without Infection B. Damage to or Obstruction of Larger Bile Ducts

Toxic liver injury Choledocholithiasis

Drug toxicity (eg, acetaminophen) Sclerosing cholangitis

Halothane hepatitis AIDS cholangiopathy

Alcoholic hepatitis Hepatic arterial chemotherapy

Iron overload (hemochromatosis) Postsurgical strictures

Copper overload (Wilson disease) Bile duct cancers

Autoimmune hepatitis Developmental disorders of the bile ducts (eg, Caroli)

Extrinsic compression of the bile duct

Tumors

Acute pancreatitis

C. Metabolic Dysfunction C. Diffuse Infiltrative Diseases

Ischemia ("shock liver") Granulomatous diseases

Acute fatty liver of pregnancy Sarcoidosis

Alpha-1 antitrypsin deficiency Disseminated mycobacterial infections

Preeclampsia Lymphoma

Reye syndrome Wegener granulomatosis

Total parenteral nutrition Amyloidosis

Diffuse malignancy
 D. Inborn Errors of Metabolism D. Diseases that Interfere with Biliary Secretion of
Bilirubin

Dubin-Johnson syndrome Drug-induced cholestasis, as with the following:

Rotor syndrome Chlorpromazine

Benign recurrent cholestasis Erythromycin

Estrogens

Anabolic steroids

Many others

Physical:

 The first manifestation commonly is a brownish discoloration of the urine. Although

scleral icterus also may be present, this typically reflects the unconjugated fraction of
bilirubin that binds tissues much more avidly.

 If sufficient unconjugated bilirubin is present, the skin, sclerae, and mucous

membranes take on a yellow cast, although this may be difficult to detect if tissues are
pigmented naturally.

 Depending on the underlying illness, stigmata of chronic liver disease may or may not
be present.

 Palpation of the abdomen may reveal the following:

o A mass (eg, a distended gallbladder, abdominal tumors)

o Tenderness over the liver (eg, as in cases of hepatitis or hepatic distension

resulting from congestion or infiltrative disease)

o Tenderness over the gallbladder fossa (as occurs in cases of biliary disease or
infection)

 In cases of biliary obstruction or stasis, stool may be acholic and light gray.

 Unexplained darkening of the skin, diabetes, or heart failure suggests

hemochromatosis.

 Kaiser-Fleisher rings or a low serum ceruloplasmin concentration suggests Wilson

disease.

 Cutaneous or neurologic findings of chronic alcoholism may be helpful diagnostic

findings.
 DIFFERENTIALS Section 4 of 8
Author Information Introduction Clinical Differentials Workup Treatment Follow-up Bibliography

Alcoholic Hepatitis
Amyloidosis, Overview
Autoimmune Hepatitis
Biliary Obstruction
Cardiac Cirrhosis
Cholangiocarcinoma
Cholangitis
Cholecystitis
Choledocholithiasis
Cirrhosis
Cytomegalovirus
Dubin-Johnson Syndrome
Graft Versus Host Disease
Hemochromatosis
Hepatic Failure
Hepatitis, Viral
Miliary Tuberculosis
Pancreatic Cancer
Pancreatitis, Acute
Primary Biliary Cirrhosis
Sarcoidosis
Septic Shock
Shock, Hemorrhagic
Tricuspid Regurgitation
Wilson Disease

Other Problems to be Considered:

 CMV hepatitis

 Drug toxicity, especially the following: acetaminophen, allopurinol, anabolic steroids,

chlorpromazine,
estrogens, halothane, isoniazid, methyldopa, phenytoin, protease inhibitors, quinidine,
rifampicin, statins, sulfa drugs
 Exposure to environmental hepatotoxins (eg, beryllium, "nutraceuticals" [eg, herbal
tea], organic solvents)
 Acute fatty liver of pregnancy
 Inherited disorders of bilirubin conjugation (eg, Rotor syndrome)
 Liver congestion
 Liver ischemia (shock liver)
 Rejection of transplanted liver
 Reye syndrome
 Total parenteral nutrition (TPN) toxicity
 Veno-occlusive disease associated with chemotherapy

Quick Find
Author Information
Introduction
Clinical
Differentials
Workup
Treatment
Follow-up
Bibliography

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Overview

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Cirrhosis

Cytomegalovirus

Dubin-Johnson
Syndrome

Graft Versus Host

Disease

Hemochromatosis

Hepatic Failure
Hepatitis, Viral

Miliary Tuberculosis

Pancreatic Cancer

Pancreatitis, Acute

Primary Biliary
Cirrhosis

Sarcoidosis

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Shock, Hemorrhagic

Tricuspid
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WORKUP Section 5 of 8
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Lab Studies:

 Appropriate initial laboratory testing depends on clinical history and physical

examination.

 All patients should receive the following:

o CBC count to screen for hemolysis

o Serum aminotransferases (aspartate aminotransferase [AST], alanine

aminotransferase [ALT])
 o Serologic screen for hepatitis, including hepatitis C virus antibody, and
hepatitis B surface antigen or antihepatitis B core antibody

o Alkaline phosphatase: If elevated or if an obstruction is suspected, images of

the bile ducts should be obtained. Gamma-glutamyl transpeptidase (GGTP)
may help differentiate a hepatic source from bone or other causes.

o Fractionated bilirubin

o Blood alcohol or acetaminophen levels upon admission (may be useful in

certain cases): Test for antimitochondrial antibodies when considering primary
biliary cirrhosis.

o Antinuclear antibodies, smooth-muscle antibodies, and other serologic studies

when considering autoimmune hepatitis

o Iron and genetic studies when considering hemochromatosis.

o Copper studies when considering Wilson disease

o Alpha-1 trypsin and other studies when considering hereditary liver diseases

Imaging Studies:

 Abdominal ultrasound should be performed to exclude biliary obstruction and to

evaluate the liver parenchyma.

o Advantages
 Safe
 Noninvasive
 Portable
 Provides good visualization of gallbladder, bile ducts, and cystic
lesions
 Can detect parenchymal liver disease, such as cirrhosis or infiltration,
and signs of portal hypertension

o Disadvantages
 Limited resolution
 Because of bowel gas, may not detect common duct stones

 Abdominal CT scans provide additional information about patients with abnormal

ultrasound scans, but they may be the initial imaging test in some cases.

o Advantages
 Better resolution
 Provides good evaluation of the entire bile duct
 Can define the anatomy better, especially if contrast agents are used
 Better for evaluating suspected malignancies, especially with
evaluation of the arterial phase
 Permits guided needle biopsies
 o Disadvantages
 More expensive and less portable than sonography
 Requires radiation exposure
 Requires IV contrast for best results
 Less sensitive than ultrasound for gallbladder stones

 Abdominal magnetic resonance imaging (MRI) produces images comparable in

quality to CT scan images, and, as technology improves, MRI may be able to provide
even more information.

o Advantages
 Requires no exposure to ionizing radiation (ie, safe in pregnancy)
 Permits multiple contrast agents and multiple scanning techniques,
which enhance potential information content
 Permits guided needle biopsies (open MRI systems only)
 With special study, can evaluate bile duct

o Disadvantages
 Expensive
 Not universally available
 Cannot be used in most patients with metallic implants
 Requires IV contrast for best results
 Currently, clinical experience limited

 Endoscopic retrograde cholangiopancreatography (ERCP) is useful in cases where

biliary obstruction is strongly suspected. It is the investigation of choice to detect
common bile duct stones and also is useful for making a diagnosis of pancreatic
cancer. Other conditions in which ERCP may be useful include primary sclerosing
cholangitis and the presence of choledochal cysts.

o Advantages
 Allows treatment of obstruction using sphincterotomy, stone extraction,
stent placement, or balloon-dilation of strictures
 Permits biopsies under direct visualization
 Provides excellent visualization of bile ducts

o Disadvantages
 Requires conscious sedation and radiation exposure
 Not always successful, especially after gastroduodenal surgery

 Percutaneous transhepatic cholangiography (PTC) offers most of the diagnostic and

therapeutic possibilities of ERCP and may be more readily available in some settings.
It can be useful in cases in which ERCP has been unsuccessful.

o Advantages
 Successful in most cases of biliary obstruction
 Allows treatment of obstruction by stone extraction, balloon-dilation of
strictures, or stent placement
 Permits biopsies or brush cytology
 Provides excellent visualization of bile ducts
 o Disadvantages
 Typically more invasive than ERCP
 Normally successful only when bile ducts are dilated
 Requires radiation exposure and use of contrast

TREATMENT Section 6 of 8
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Consultations:

 In most patients, the cause of conjugated hyperbilirubinemia is apparent, such as those

with viral hepatitis or sepsis.

 When this is not the case or when multiple causes are possible, consultation with a
gastroenterologist or hepatologist may be helpful.

FOLLOW-UP Section 7 of 8
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Patient Education:

 For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and
Pancreas Center and Hepatitis Center. Also, see eMedicine's patient education articles
Cirrhosis, Gallstones, and Newborn Jaundice.