Caroli Disease is a rare inherited
disorder characterized by abnormal widening (dilatation)
of the ducts that carry bile from the liver (intrahepatic
There are two forms of Caroli Disease.
most cases, the isolated or simple form Caroli Disease,
affected individuals experience recurrent episodes
of inflammation of the bile ducts (cholangitis) and
unusual accumulation of pus (abscesses) on the liver.
second form of Caroli Disease is associated with abnormal
formation of bands of fibrous tissue in the portal
area of the liver (congenital hepatic fibrosis). The
portal area of the liver is a groove (fissure) where
the portal vein and the hepatic artery enter the liver.
The portal vein is the blood vessel that carries blood
from the stomach, intestine, and spleen to the liver
and the hepatic artery is the blood vessel that carries
blood from the aorta. This form of Caroli Disease
is also often associated with high blood pressure
of the portal vein (portal hypertension), polycystic
kidney disease, and, in severe cases, liver failure..
This is a rare congenital disorder
that classically causes saccular ductal dilatation,
which usually is segmental. Caroli disease is associated
with recurrent bacterial cholangitis and stone formation.
Caroli disease also is known as
communicating cavernous ectasia or congenital cystic
dilatation of the intrahepatic biliary tree. It is
distinct from other diseases that cause ductal dilatation
caused by obstruction. It is not one of the many choledochal
Caroli disease is also called as
Congenital Dilatation of Intrahepatic Bile Duct.
Caroli Disease is thought to be
inherited as either an autosomal dominant or recessive
The precursor of the intrahepatic
biliary tree is a double-layered sleeve of cells known
as the ductal plate (DP). The DP first arises from
hepatocyte precursors surrounding hilar portal vein
vessels at 8 weeks' gestation, and peripheral regions
of the DP then develop sequentially. During the remainder
of gestation, a process of DP remodeling occurs in
which small areas of the double layer separate to
form tubules, which join to form the intrahepatic
biliary tree, while the remaining regions of the DP
become involuted. Caroli disease belongs to a subcategory
of diseases thought to originate from failures of
this process collectively known as ductal-plate malformation.
The patient may have a history of
intermittent abdominal pain, which reflects episodes
of bile stasis or the passage of bile stones.
Patients with cholangitis may report
fever and pain in the right upper quadrant.
In Caroli syndrome, portal hypertension
may result in hematemesis or melena.
Because Caroli syndrome is associated
with ARPKD (autosomal dominant polycystic kidney disease)
and because it appears to be inherited in an autosomal
recessive manner, the patient may have a family history
of kidney or liver disease.
levels are usually in the reference range.
levels may be slightly elevated.
CBC may reveal thrombocytopenia and leukopenia if
portal hypertension and hypersplenism are present.
An elevated WBC count or erythrocyte sedimentation
rate (ESR) may indicate cholangitis.
and BUN values should be obtained to detect associated
is the best initial imaging study because it reveals
the irregular dilatation of the large intrahepatic
bile ducts typical of Caroli disease or syndrome.
Extrahepatic biliary dilatation may also be present
as a result of prior cholelithiasis.
Doppler evaluation of the liver can be used to
detect portal hypertension.
The kidneys can also be assessed for evidence
of polycystic kidney disease.
resonance cholangiography is increasingly used to
diagnose Caroli disease or syndrome.
It provides excellent images of the intrahepatic
and extrahepatic biliary trees, and it can also
depict renal involvement.
use is currently limited by the availability of the
necessary equipment and expertise.
may be used, particularly if sonograms cannot be obtained
because of bowel gas or body habitus.
scintigraphy can be useful to document communication
between cysts and the biliary system, a feature present
in Caroli disease or syndrome but absent in polycystic
liver disease and hepatic abscesses.
modalities, such as percutaneous transhepatic cholangiography
(PTC) and endoscopic retrograde cholangiopancreatography
(ERCP), enable excellent visualization of the biliary
tree. However, these studies are limited by the risks
biopsy and culture should be performed in cases of
suspected chronic cholangitis.
has been used to identify and treat biliary stones
in patients with Caroli disease or syndrome, but it
is associated with a postprocedural risk of cholangitis.
shunting may be indicated in patients who have portal
Liver biopsy reveals the typical
pattern of ductal-plate malformation, with bile-duct
ectasia, portal-vein malformations, and fibrosis.
In Caroli syndrome, ductal-plate malformation is evident
throughout the liver, whereas only large intrahepatic
ducts are affected in relatively rare Caroli disease.
Treatment – Medical,
Therapy depends on the clinical
manifestations and the location of the biliary abnormality.
Antibiotic treatment with broad-spectrum agents is
extremely important. Prophylactic antibiotics have
had poor and unpredictable results. The addition of
oral agents such as ursodeoxycholic acid has no definite
benefit. Prevention of the complications is ideal
but no method has been proven effective.
Drainage procedures with endoscopic
retrograde cholangiopancreatography (ERCP) or percutaneous
transhepatic cholangiography (PTC) are important,
and sphincterotomy can aid biliary drainage and stone
removal or subsequent passage and may decrease bouts
of cholangitis. If the process is confined to one
lobe, lobectomy completely relieves the symptoms.
Internal surgical bypass (choledochojejunostomy, Roux-en-Y,
hepaticojejunostomy) is helpful in diffuse forms of
the disease. No cure for the disease exists.
Extracorporeal shock-wave lithotripsy
or intraductal electrohydraulic lithotripsy with biliary
drainage, stent placement, and liberal sphincterotomy
is advocated as an important but aggressive method
to treat and prevent choledocholithiasis.
Ultimately, liver transplantation
may be required. This is the best alternative when
recurrent cholangitis is not present.
Chronic Hepatitis (CAH) is ongoing
injury to the cells of the liver with inflammation
which lasts for longer than six months. The causes
of chronic hepatitis are several: viruses, metabolic
or immunologic abnormalities and medications.
Hepatitis B and C are the most
common causes of chronic hepatitis. Together they
account for more than 75 percent of the cases in the
world. Hepatitis B is far more common in China and
sub-Saharan Africa and among male homosexuals and
IV drug users.
Chronic hepatitis C behaves differently
from hepatitis B. The disease is generally mild, with
fatigue being the main symptom. However, ten or more
years later, the complications of cirrhosis appear
in some patients, sometimes unexpectedly. By contrast
with hepatitis B, the percentage of patients infected
who develop cirrhosis is much greater. While primary
liver cancer can also develop from hepatitis C, it
appears to be much less common than after hepatitis
Autoimmune Chronic Hepatitis varies
from mild to serious disease. The percentage of patients
who develop cirrhosis is high and it may appear early.
Most of the patients are young women but postmenopausal
women and males may get the disease. Only a few cases
of primary liver cancer have been reported with this
disease. Twenty-five percent of the cases of chronic
hepatitis result from damage to the liver by the immune
system. The trigger for autoimmune chronic hepatitis
is unknown, but the damage to the liver is caused
by the individual's lymphocytes and by antibodies
produced in the individual's own tissue. Autoimmune
chronic hepatitis is usually a progressive disease
ending in cirrhosis.
Hepatitis A and E (formerly called
epidemic or enteric non-A, non-B) are rarely, if ever,
responsible for causes of chronic hepatitis.
Hepatitis D infection needs the
hepatitis B virus to multiply. Hepatitis D can cause
acute hepatitis in someone who is a carrier of the
hepatitis B virus and can cause acute hepatitis at
the same time that the hepatitis B virus does. In
any event, the combination of hepatitis B and D is
worse then hepatitis B alone and is more likely to
cause serious chronic hepatitis and cirrhosis. IV
drug users have a high incidence of hepatitis D.
Viruses of the herpes family, which
cause cold sores, genital herpes, chicken pox, shingles
and infectious mononucleosis, can cause acute hepatitis,
especially when the immune system is not functioning
properly. It is unlikely that they will produce chronic
hepatitis. Other viruses, as yet undiscovered, may
be responsible for some cases of chronic hepatitis.
Few medications still in use and
several that have been withdrawn from the market can
also cause chronic hepatitis. These include: isoniazid,
used for tuberculosis; methyldopa, used for hypertension;
nitrofurantoin, used for urinary tract infections;
phenytoin, used for seizure disorders and selected
other prescription medications. These medications
must be taken for long periods of time and the number
cases of chronic hepatitis produced by these medications
Chronic hepatitis caused by drugs
is usually recognized early. Stopping the medicine
before cirrhosis has developed usually reverses the
Some inherited disorders of metabolism
also can appear as chronic hepatitis. The most frequent
of these conditions is Wilson's disease, a familial
disorder of copper metabolism. Alpha-1-antitrypsin
deficiency and tyrosinemia may appear as chronic hepatitis
although other features help in distinguishing these
rare conditions from those caused by viruses.
Symptoms result from the liver
cell injury, the inflammation or from the resulting
scarring which is called cirrhosis. Chronic hepatitis
may follow acute hepatitis B or C (formerly called
non-A, non-B) or may develop quietly without an acute
Liver biopsy is helpful in that
it confirms the diagnosis, aids in establishing the
cause (etiology) and can demonstrate the presence
of cirrhosis. It is less helpful in judging the response
Fatigue, mild discomfort in the
upper abdomen, loss of appetite and aching joints
are the common symptoms of chronic hepatitis. Fatigue
is by far the most common symptom and it might be
quite disabling. Often it gets worse as the day wears
on. Some patients, however, may have no symptoms.
Others may have signs of liver failure, inducing jaundice,
abdominal swelling (due to fluid retention called
ascites), or coma, depending on the severity of the
liver disease and whether or not cirrhosis has developed.
Most complications are vague and may be mistaken for
other diseases or simply a consequence of aging. Disorders
of other organs like the thyroid, intestine, eyes,
joints, blood, spleen, kidneys and skin may occur
in about 20 percent of patients depending on the cause
of the chronic hepatitis.
When the hepatitis is mild and
limited in extent, it is called chronic persistent
hepatitis (CPH). When it is more extensive and seems
to be destroying the cells of the liver, it is called
chronic active hepatitis (CAH).
Treatment : Medical, Surgical
Interferon has been approved for
the treatment of hepatitis B and C. The treatment
has been shown to reduce the inflammation and liver
damage caused by the virus in 25-30% of cases by eliminating
the virus, thus reducing the development of scar tissue
and avoiding the development of cirrhosis.
In people treated with interferon
studies show that 50% will respond to treatment and
50% of those patients will relapse when interferon
is stopped. Research is going on to address the relapse
Additional clinical trials are
being conducted to identify the most effective dose
and duration of therapy with interferon. Studies are
continuing in an attempt to reduce the side effects
of the medication that exists. These include "flu-like"
symptoms, and less often, fever, depression, hair
loss, nausea and vomiting. Currently, the treatment
consists of an injection three times a week over a
period of six months. Blood tests are needed to monitor
progress during treatment and a liver biopsy (retrieving
a small specimen of the liver through a needle inserted
into the liver) is an accepted procedure prior to
and following treatment.
Fifty percent of the patients treated
will experience remission of the disease. When the
treatment is stopped 50 percent will relapse. However,
only about 20 percent of untreated patients will go
on to develop cirrhosis over a period of years. Research
into the management of those who relapse is ongoing.
Interferon does not seem to work
well in patients:
with substance abuse (alcohol or illegal drugs),
who are not very sick,
whose test results are not very abnormal,
whose immune system is not functioning well because
with hepatitis B who were infected from their mothers
carriers who are no longer contagious or infectious,
with significant heart, lung or kidney diseases,
or couples who are trying to conceive.
Knowing the cause of the disease is helpful in estimating
the prognosis. Only a small percentage of patients
with chronic hepatitis B develop cirrhosis. In those
patients, cirrhosis develops early in the course of
the disease with complications appearing in the first
few years. Chronic hepatitis often causes acute hepatitis
or flare-ups and periods with no signs. Scarring becomes
more extensive with each flare-up. Patients in the
Orient have about a 15 percent chance of developing
primary liver cancer, usually after the age of 50
with men more likely candidates than women. This complication
is much less common in the Western World.
The disease becomes life-threatening only after
cirrhosis has developed. More than half of all patients
live at least 15 years from the time of the first
diagnosis and this number is continuously improving.
Previously, prognosis was thought to depend on what
was found on liver biopsy. This is now only partly
true. Prognosis is worse and complications more numerous
and severe if cirrhosis has already developed. Much
attention has been paid to the location and extent
of the inflammation of the liver.
Steroid therapy remains the only useful treatment
for autoimmune disease, but it may have to be given
for a lifetime and may also not prevent the ultimate
development of cirrhosis.
Liver transplantation has become an accepted form
of therapy when chronic hepatitis becomes life-threatening,
usually as a result of complications of cirrhosis.
Recurrence of hepatitis C or autoimmune hepatitis
does not seem to occur, but hepatitis B, if virus
is still present and the patient is contagious, will
recur in the new liver and often be acute. Attempts
are being made to prevent this recurrence.
The most important treatment for hepatitis B is
prevention. Hepatitis B vaccines should be given to
all who are exposed to this disease on a regular basis.
All pregnant women should be tested for hepatitis
B. Carriers of hepatitis B, many of them unaware that
they are infected, can pass it on to their babies
as well as their sexual contacts. All newborns should
be vaccinated against hepatitis B. Three injections
are needed to provide adequate immunity.
An important aspect of treatment is supportive care.
Diet should be well balanced. The use of high carbohydrate,
high protein or low fat diets have no scientific basis,
and in some instances, such diets may be harmful.
Vitamin and mineral supplementation also has no place
in the management of chronic hepatitis unless some
deficiency is present. No substance is known that
will help the main symptom, fatigue. However, a good
physical fitness program may lessen this distressing
symptom. Patients should be advised to limit the amount
of salt that they use in an attempt to forestall the
accumulation of fluids as ascites or ankle swelling.
Since almost all drugs must be detoxified by the liver,
and since the injured liver does not perform this
task well, limiting the amount of drugs that a patient
uses to only essential ones is important. This includes
discouraging the use of sedatives and tranquilizers.
and Quality of Life
Learning more about the viruses responsible for
chronic hepatitis and how to control them will occur
in the next decade. Similarly, learning about the
body's immune system and how to control it has already
begun. Preventive efforts will be enhanced so that
fewer cases of chronic hepatitis will develop. The
goal of eliminating this group of diseases seems to
be just over the horizon, and while our skills at
transplantation are rapidly increasing, the form of
therapy for chronic hepatitis, like the disease itself,
of the Liver
The most common benign tumor of
the liver is a cavernous hemangioma. This tumor, as
well as other benign tumors, is typically found by
chance on an imaging study of the liver, such as ultrasound
or computed tomography (CT). Cavernous hemangioma
can be diagnosed with reasonable accuracy by the use
of various imaging tests. Unless it is extremely large,
no specific therapy is usually required. This tumor
may enlarge in women taking hormone pills; thus, physicians
will often recommend discontinuing birth control pills
or postmenopausal hormone replacement therapy.
The other common benign tumors of
the liver are called hepatocellular adenoma and focal
nodular hyperplasia. Both of these tumors are also
usually found by chance, although hepatocellular adenoma
has a substantial risk of bleeding within the tumor
and into the peritoneal (abdominal) cavity. The use
of a number of imaging tests, and occasionally hepatic
arteriography or biopsy, may be required to make the
diagnosis of this tumor. Hepatocellular adenomas are
also quite sensitive to hormonal therapy and may regress
when birth control pills or hormones are stopped.
If feasible, removal of hepatic adenoma may be recommended
if it is large in order to prevent the possibility
of bleeding and/or rupture.
The most common primary malignant
tumor of the liver is a hepatocellular carcinoma.
Primary liver cancer accounts for less than 1 percent
of all cancers in this country. However, in other
parts of the world such as Africa, Southeast Asia,
and China, it is a major health problem, causing up
to 50 percent of cancer cases seen in those areas.
This difference is thought to be due to the much higher
percentage of the population who are carriers of the
hepatitis B virus, which predisposes to the development
of hepatocellular carcinoma.
It was recognized a number of years
ago that chronic carriers of the hepatitis B virus,
particularly those with chronic hepatitis or cirrhosis,
are at substantially increased risk to develop hepatocellular
carcinoma. Recent evidence indicates that patients
who have long-standing chronic hepatitis C virus infection
are also at increased risk for the development of
hepatocellular carcinoma, although the exact risk
Certain toxins and chemicals are
also rarely associated with liver cancer. In Africa,
aflatoxin, a product of mold found in badly stored
peanuts or other foods, has been recognized as a cause
of liver cancer. Finally, certain diseases other than
chronic hepatitis B or C are associated with an increased
risk of hepatocellular carcinoma. Iron overload cirrhosis
(hemochromatosis) is associated with a substantial
risk of hepatocellular carcinoma once cirrhosis has
developed. Patients with long-standing alcoholic cirrhosis
are also at risk for developing this tumor. Two congenital
disorders, alpha-1-antitrypsin deficiency and tyrosinemia,
may also be complicated by the development of hepatocellular
Metastatic or secondary tumors of
the liver come from cancers originating elsewhere
in the body. Because the liver filters blood from
all parts of the body, it is often the site in which
cancer cells will lodge and develop into metastatic
nodules. An enlarged liver secondary to cancer may
be an early sign of cancer in other organs. Secondary
or metastatic cancer should not be confused with primary
cancer of the liver.
Primary liver cancer may be detected
by screening high risk patients or by chance on an
imaging study of the abdomen performed for another
reason, or it may be detected because of symptoms
such as abdominal pain. Studies performed in several
countries have demonstrated that the periodic use
of abdominal ultrasound and a blood tumor marker,
called alpha-fetoprotein, may lead to the early detection
of small hepatocellular carcinomas in patients at
high risk. This screening strategy has not been widely
adopted because its cost-effectiveness has yet to
be proven. In patients who develop symptoms from more
advanced hepatocellular carcinoma, weight loss, periodic
severe pain and other generalized symptoms may occur.
Health may deteriorate rapidly and jaundice (yellow
skin) may appear.
The diagnosis of primary cancer
of the liver is typically made by liver imaging tests,
such as abdominal ultrasound and CT scan in combination
with the measurement of blood levels of alpha-fetoprotein.
The final diagnosis is confirmed by needle biopsy,
which is typically performed by a radiologist who
can direct the biopsy needle to the exact position
of the tumor. It may be necessary to also examine
the arteries and veins of the liver by hepatic arteriography,
particularly if surgery is considered.
: Medical, Surgical
Treatment of primary cancer of the
liver may be directed towards a cure, or focused at
palliation (the relief of symptoms and prolongation
of life). When the tumor is small and limited to one
lobe of the liver, surgical removal offers a chance
of cure. If the tumor is larger or involves more than
one lobe of the liver such that it cannot be removed,
liver transplantation has also been performed. In
either case, the cure rate averages only 20-30 percent,
which has limited somewhat the use of liver transplantation
for this problem.
There are a number of newer therapies
that offer good palliation for hepatocellular carcinoma.
In particular, the direct injection of alcohol into
the tumor via a small needle or the embolization at
the time of hepatic arteriography of a specific chemotherapeutic
agent (chemo-embolization) has resulted in prolonged
survivals. These measures may also be used together
with either surgical resection or liver transplantation.
Cirrhosis is a term that refers to a group of chronic
liver diseases in which normal liver cells are damaged
and replaced by scar tissue, decreasing the amount
of normal liver tissue. The distortion of the normal
liver structure by the scar tissue interferes with
the flow of blood through the liver. It also handicaps
the function of the liver which, with the loss of
normal liver tissue, leads to failure of the liver
to perform some of its critically important functions.
Cirrhosis and other liver diseases take the lives
of over 25,000 Americans each year and rank eighth
as a cause of death.
There are a number of conditions that can lead to
Alcohol consumption While almost everyone who drinks
excessive amounts of alcohol sustains some liver damage,
it does not necessarily develop into cirrhosis. In
those individuals who drink one-half to one pint (8
to 16 ounces) of hard liquor per day (or the equivalent
in other alcoholic drinks), for 15 years or more,
about one-third develop cirrhosis. Another third develop
fatty livers, while the remainder have only minor
liver problems. In general, the more you drink, the
greater the frequency and regularity of excessive
intake, the more likely that cirrhosis will result.
A poor diet, long considered to be the main factor
in the development of cirrhosis in the alcoholic,
is probably only a contributing factor. Alcohol by
itself, in large amounts, is a poison which can cause
Acute hepatitis A and acute hepatitis E do not lead
to chronic hepatitis. Acute hepatitis B leads to chronic
infection in approximately 5 percent of adult patients.
In a few of these patients, the chronic hepatitis
B progresses to cirrhosis.
Acute hepatitis D infects individuals already infected
by hepatitis B.
Acute hepatitis C becomes chronic in approximately
80 percent of adults. A minority of these patients
(20-30 percent) will progress to cirrhosis, typically
over many years.
Hemochromatosis - abnormal accumulation
of iron in the liver and other organs because of the
increased absorption of iron from the intestine.
Wilson's disease - abnormal accumulation
of copper in the liver and other organs due to the
decreased excretion of copper from the liver.
Alpha1-antitrypsin deficiency--inherited absence of
a specific enzyme in the liver.
Glycogen storage diseases - inability
to properly utilize sugars.
Autoimmune hepatitis prolonged
obstruction or other diseases of the bile ducts (biliary
cirrhosis, sclerosing cholangitis) prolonged exposure
to environmental toxins
Some forms of heart disease (cardiac cirrhosis)
severe reaction to drugs schistosomiasis (parasitic
The onset of cirrhosis is often "silent"
with few specific symptoms to identify what is happening
in the liver. As continued scarring and destruction
occur, the following signs and symptoms may appear:
Loss of appetite
Nausea and vomiting
Enlargement of the liver
Jaundice--yellow discoloration of the whites of the
eyes and skin occurs because bile pigment can no longer
be removed by the liver
Itching - due to the retention of bile products in
Ascites--abdominal swelling due to an accumulation
of fluid caused by the obstruction
of blood flow through the liver
Vomiting of blood--frequently occurs from swollen,
ruptured varices (veins that burst) in
the lower end of the esophagus due to the increased
pressure in these vessels caused by scar tissue formation
Increased sensitivity to drugs--due to inability of
the liver to inactivate them
Encephalopathy (impending coma) - subtle mental changes
advancing to profound confusion
Many patients may have no symptoms and are found
to have cirrhosis by physical examination and laboratory
tests, which may have been performed in the course
of treatment for unrelated illnesses.
In alcoholic cirrhosis
History of regular and excessive alcoholic intake
physical and behavioral changes examination of liver
tissue obtained by needle biopsy under local anesthesia
In active viral hepatitis
Treatment : Medical,
Treatment depends on the type and stage of the cirrhosis.
It aims at stopping the progress of the cirrhosis,
reversing (to whatever extent possible) the damage
which has already occurred, and treating complications
that are disabling or life-threatening. Stopping or
reversing the process requires removal of the cause.
In alcoholic cirrhosis
abstinence from alcohol
an adequate, wholesome diet
In cirrhosis caused
by viral hepatitis
an approved approach is the use of interferon to improve
immune responses to viral infection.
Experts estimate that more than half of all liver
diseases could be prevented if people acted upon the
knowledge we already have.
Each year more than 25 million Americans are afflicted
with liver and gallbladder diseases and more than
25,000 die of chronic liver disease and cirrhosis.
There are few effective treatments for most life-threatening
liver diseases, except for liver transplants. Meanwhile,
patients and their families must cope with medical,
financial and emotional problems.
Research has recently opened up exciting new paths
for investigation, but much more remains to be done
to find cures for more than 100 different liver diseases
and help millions of Americans who are suffering.
To increase the number of liver researchers, the American
Liver Foundation encourages young scientific investigators
to pursue careers in liver research by supporting
bright, highly trained men and women in their quest
for answers. Research and education have made a difference.
When the Foundation first became operational in 1979,
reported deaths due to chronic liver diseases and
cirrhosis exceeded 50,000 each year. By 1992, that
figure was reduced to 26,000.
Concerned contributors like you have enabled us
to increase Foundation-supported research tenfold
In the past year the Foundation has counselled,
encouraged, and informed over 35,000 anxious victims
of liver disease. We distributed two million brochures
to patients and referred hundreds to medical specialists.
We thank you for your thoughtful support and confidence
in our efforts. You have enabled us to touch the lives
of millions of Americans who look to the American
Liver Foundation for guidance, support and encouragement.
In certain types
of cirrhosis caused by autoimmune hepatitis
corticosteroids alone or with azathioprine may be
an effective treatment
In cirrhotic patients
supplemental fat soluble vitamins may be helpful
removal of excessive copper by drugs that deplete
the body's copper
removal of excess iron by phlebotomy (removal of one
pint of blood per week)
Most types of cirrhosis
liver transplantation with replacement of the diseased
organ when advanced liver failure occurs
and Quality of Life
Complications of cirrhosis include ascites, coma
and hemorrhage from esophageal varices.
Ascites is treated by reducing the intake of salt
and the administration of drugs
to improve excretion of salt and water (diuretics).
In some instances, large amounts
of fluid are removed by direct catheter drainage
through the abdominal wall (large volume paracentesis)
Treatment of coma, or impending coma (encephalopathy),
includes specific medications, reducing
the intake of protein foods, and control of
Treatment of hemorrhage from varices (internal varicose
veins) includes sclerotherapy (injection of the enlarged
vein with a chemical that causes scarring). Other
treatments include: drugs to reduce the likelihood
of bleeding or rebleeding, compression of the bleeding
varices with a specially constructed balloon, and
a new radiological procedure called transjugular intrahepatic
portosystemic shunt (TIPS).
Treatment at this stage, with proper adherence to
the physician's recommendations, leads to improvement
in the majority of cases and the patient is able to
pursue a normal life and activities.
When cirrhosis is not discovered until extensive
damage has resulted, the outlook may be less favorable
for improvement, and complications such as ascites
and hemorrhage are more likely to be encountered.
The liver is a large organ and is able to perform
its vital functions despite some damage. It also has
the ability to repair itself to a limited degree.
Cells that die are replaced by new cells. If the cause
of cirrhosis can be removed, these factors provide
hope for both improvement and carrying on a normal
An increasing number of scientific investigators
conducting liver research give hope for new breakthroughs
in treatment, management and cures for liver diseases
in the foreseeable future.
Crigler-Najjar syndrome (CNS) is an inherited disorder
in which bilirubin (a substance made by the liver)
cannot be changed into its water-soluble form, bilirubin
glucuronide. This causes jaundice (yellow discoloration
of skin and eyes) and organ malfunctions.
Alternative names to CNS are Glucuronyl transferase
deficiency (type I Crigler-Najjar) and Arias syndrome
(type II Crigler-Najjar).
Type 1 CNS is associated with neonatal jaundice and
neurologic manifestations, whereas type 2 CNS manifests
as a lower serum bilirubin level. Affected individuals
may survive to adulthood without any neurological
Crigler-Najjar is a very rare disease. There are
less than 50 known cases in the USA, and less than
200 worldwide. It is named after Dr. Crigler and Dr.
Najjar who discovered the disease.
Crigler-Najjar syndrome is caused by an abnormal
gene which fails to produce a functional enzyme (bilirubin
glucuronyltransferase) capable of converting bilirubin
into a water-soluble and therefore, easily excreted
form. As a result, bilirubin can build up in the body,
which can damage the brain and other organs.
The syndrome is inherited as an autosomal recessive
trait. This means that the child must get the defective
gene from both parents to develop the severe form
of the condition. Parents who are carriers (with just
one defective gene) have about half the enzyme activity
of a normal adult.
Infants who inherit the trait from both parents (this
is called being homozygous for the abnormal gene)
develop severe jaundice (hyperbilirubinemia) beginning
a few days after birth. If these infants are not treated,
they may develop kernicterus, which is bilirubin toxicity
of the brain and can be fatal.
In such infants, the jaundice will persist into adult
life and may require daily treatment. The constantly
elevated levels of bilirubin may eventually produce
an adult form of kernicterus despite treatment. If
left untreated, this severe infant-onset form of the
disease will lead to death in childhood.
Milder forms of the disease (type II) are not associated
with severe toxicity, liver damage, or changes in
thinking during childhood. Affected individuals still
have jaundice, but they have fewer symptoms and less
family history of Crigler-Najjar syndrome
skin (jaundice) and eyes (icterus) that begins on
the 2nd or 3rd day of life and progressively worsens
that persists beyond 2 weeks of life without an obvious
and changes in thinking (resulting from brain toxicity
1 is associated with the production of little or no
UGT, which causes very high levels of bilirubin to
build up in the body. Jaundice, the yellowish appearance
of the skin and eyes due to the excess bilirubin,
is present at or soon after birth.
2 is associated with low UGT activity, and therefore
lower levels of bilirubin in the body than in type
1. Jaundice may not appear until later in infancy
Crigler-Najjar syndrome type 1 is not identified and
treated at birth, the excess bilirubin may cause brain
damage, known as bilirubin encephalopathy or kernicterus.
Symptoms of kernicterus are low muscle tone (hypotonia),
deafness, and lethargy; death or permanent brain damage
Tests used to evaluate the liver function include:
Unconjugated bilirubin in blood (would be highly elevated)
Total bilirubin level (would be high)
Conjugated bilirubin (would be low to absent)
Liver biopsy, enzyme assay for low-absent Glucuronyl
A family history of Crigler-Najjar syndrome
Infants with Type 1 will be jaundiced and have bilirubin
levels of 17-50 mg/dL.
Crigler-Najjar syndrome Type 2 may be suspected in
infants and children who are jaundiced and have bilirubin
levels of 6-22 mg/dL.
Treatment - Medical, Surgical
Medical Treatment :
Patients with type 2 CNS may not require any treatment
or can be managed with phenobarbital. By contrast,
prompt treatment of kernicterus is required in patients
with type 1 CNS to avoid the potentially devastating
management of bilirubin encephalopathy involves plasma
exchange transfusion, which acts by removing the bilirubin-saturated
albumin and provides free protein, which draws bilirubin
from the tissues.
exchange should be accompanied by long-term phototherapy,
which helps in the conversion of bilirubin to more
soluble isoforms that can be excreted in the urine.
Oral calcium phosphate may be a useful adjuvant to
phototherapy in type 1 CNS.
based on gene and cell transfer techniques, although
largely experimental at the present time, are likely
to play an important role in the management of CNS
in the future.
of heme oxygenase, such as tin protoporphyrin or tin-mesoporphyrin,
may be helpful in reducing bilirubin levels emergently,
but the effect is short-lived.
is needed on an ongoing basis throughout life. In
infants this is done using bilirubin lights (bili
or 'blue' lights)
becomes less successful after 4 years because thickened
skin blocks the light.
Liver transplantation has been attempted in select
patients with type 1 CNS and has achieved good success
Life expectancy and
Quality of Life
Genetic counseling is recommended for prospective
parents with a family history of Crigler-Najjar syndrome.
People who carry the gene can be recognized by blood
The majority die with kernicterus in the first year