Biliary atresia is a serious disease of the very young
infant. It results in inflammation and obstruction
of the ducts which carry bile from the liver into
the intestine. When bile cannot flow normally, it
backs up in the liver (a situation called biliary
"stasis"). This causes "jaundice,"
or a yellowing of the skin, and cirrhosis. Cirrhosis
occurs when healthy liver cells are destroyed, in
this case by disease, and replaced with scar tissue.
This scarring interferes with blood flow through the
liver, causing more cell damage and scarring.
The cause of biliary atresia has not yet been discovered.
The disease affects approximately one infant in every
20,000 live births. Girls are affected slightly more
often than boys, but no racial or ethnic group appears
to be more affected than any other.
Biliary atresia is not a hereditary condition (although
in some very rare cases, more than one infant in a
family may be affected). Many parents experience feelings
of guilt, but they should be reassured that nothing
they have done caused their child's illness.
The symptoms of biliary atresia are usually evident
between two and six weeks after birth. The baby will
appear jaundiced, and may develop a large, hardened
liver and a swollen abdomen. The stools are usually
pale grey and the urine appears dark.
Some babies may develop intense itching, or "pruritus,"
which makes them extremely uncomfortable and irritable.
The exact cause of this itching is not yet known,
although researchers have found a connection between
it and the backup of bile.
There are many liver diseases which cause symptoms
similar to those of biliary atresia. Consequently,
many tests may have to be performed before biliary
atresia can be diagnosed conclusively.
Every effort should be made to search for any of the
causes of jaundice which might be confused with biliary
atresia. This involves blood and urine tests; liver
function tests; blood counts and a test for clotting
function. A painless examination using ultrasound
(ECHO) is often done to study the liver and determine
the size of the bile ducts and gallbladder.
Other tests which are often used are specialized X-ray
techniques or radioactive scans of the liver which
can be helpful in focusing on the true abnormality.
A liver biopsy, in which a tiny sample of the liver
is removed with a needle, allows the physician to
examine the liver tissue microscopically.
The most successful treatment for biliary atresia
to date is a type of surgery which creates drainage
of bile from the liver when the ducts have become
completely obstructed. This operation is called the
Kasai procedure (hepatoportoenterostomy) after Dr.
Morio Kasai, the Japanese surgeon who developed it.
In the Kasai procedure, the surgeon removes the damaged
ducts outside of the liver (extrahepatic) and replaces
them with a length of the baby's own intestine, which
acts as a new duct.
The aim of the Kasai procedure is to allow excretion
of bile from the liver into the intestine via the
new duct. The operation accomplishes this about 50
percent of the time. In those who respond well, jaundice
usually disappears after several weeks.
In the remaining 50 percent of cases where the Kasai
procedure does not work, the problem often lies in
the fact that obstructed bile ducts are "intrahepatic"
or inside the liver, as well as outside. No procedure
has yet been developed to correct this problem except
Liver transplantation is an option which is becoming
increasingly useful to victims of certain liver diseases.
The survival rates for transplant recipients have
increased dramatically with improved surgical techniques
and the development of new drugs which help overcome
the problem of organ rejection.
In children with biliary atresia, liver transplantation
is generally not attempted until the Kasai procedure
has been performed. If this operation is not successful,
and before complications of the resulting cirrhosis
become severe and life threatening, liver transplantation
may be attempted. It has been successful in numerous
cases. However, as in all organ transplantation, success
depends greatly upon the timely availability of suitably
matched organs for donation, the time factor involved
(a donated liver must be used within 16 hours for
the operation to be successful), and other factors
which are only now being investigated. The use of
reduced-size and living-related transplants are aiding
in the timing and availability of suitable donor organs.
Life expectancy and
Quality of Life
The aim of treatment after surgery is to encourage
normal growth and development. If bile flow is good,
the child is given a regular diet. If bile flow is
reduced, a low fat diet is recommended as bile is
required to aid in the absorption of fats and vitamins.
Multiple vitamins, vitamin B complex, and vitamins
E, D, and K can be given as supplements.
Unfortunately, despite bile flow, the Kasai procedure
is not a cure for biliary atresia. For reasons which
are still unknown, liver damage often continues and,
eventually, cirrhosis and its complications appear.
The extent and type of liver damage differ in each
baby with biliary atresia. Some infants respond to
the Kasai procedure; others do not. If bile continues
to flow, long-term survival is possible. However,
it is presently impossible for a physician to determine
in advance which baby is likely to respond to treatment.
Budd-Chiari syndrome is a rare disorder
caused by blood clots that completely or partially
block the large veins that carry blood from the liver
Budd-Chiari syndrome is an uncommon
condition induced by thrombotic or nonthrombotic obstruction
to hepatic venous outflow. Budd described it in 1845,
and Chiari added the first pathologic description
of a liver with "obliterating endophlebitis of
the hepatic veins" in 1899. Hepatomegaly, ascites,
and abdominal pain characterize Budd-Chiari syndrome.
The syndrome most often occurs
in patients with underlying thrombotic diathesis,
including myeloproliferative disorders such as polycythemia
vera and paroxysmal nocturnal hemoglobinuria, pregnancy,
tumors, chronic inflammatory diseases, clotting disorders,
Usually, the cause of Budd-Chiari
syndrome is not known. Some affected people have a
blood clotting disorder or sickle cell disease or
are pregnant. Direct pressure on the veins, which
may result from injury, liver abscess (a pus-filled
pocket of infection), liver cancer, or kidney cancer
(which can press on the hepatic veins), also increases
the likelihood of developing blood clots.
Obstruction of intrahepatic veins
leads to congestive hepatopathy. This results from
obstruction of either large- or small-caliber veins,
which leads to hepatic congestion as blood flows into,
but not out of, the liver. Hepatocellular injury results
from microvascular ischemia due to congestion. Portal
hypertension and liver insufficiency result.
The symptoms of Budd-Chiari syndrome
may begin suddenly and severely, but usually they
begin gradually. The liver swells with blood and becomes
tender. The blood accumulation in the liver raises
the pressure in the portal vein, although the consequences
may not develop for months. One such consequence of
this raised pressure is the formation of dilated,
twisted (varicose) veins in the esophagus (esophageal
varices), which may rupture and bleed, sometimes massively,
often with vomiting of blood. In addition, fluid leaks
from the surface of the swollen liver into the abdominal
cavity (ascites), and abdominal pain and mild jaundice
(a yellowish discoloration of the skin and the whites
of the eyes) occur.
Within a few days to several months,
other symptoms of liver failure may occur. The blood
clots occasionally extend to block the inferior vena
cava—the largest vein entering the heart. This
blockage causes considerable swelling in the legs
Early diagnosis can be achieved
by sonography or CT scan, the latter giving a typical
image with stagnation of contrast material. Cavography
is highly recommended to select the best procedure
and to identify possible involvement of the vena cava.
At the same time, pressure measurements along the
vena cava and in the hepatic veins - if accessible
- should be performed.
Finally, liver biopsy should be
obtained to document cirrhosis or absence thereof
since this may influence the choice of treatment.
A recent study found that biopsy contained no prognostic
information, but there were only 4 % of patients with
Treatment – Medical,
If the vein is narrowed rather than
blocked, anticoagulants (drugs that prevent clots)
or thrombolytics (drugs that dissolve clots) may be
used. If esophageal varices develop and bleed, surgery
may be performed to reduce the pressure in the portal
vein. During surgery, the portal vein is connected
to the inferior vena cava, causing blood flow to bypass
the liver. However, this newly created connection
(shunt) can increase the risk of liver encephalopathy
(brain damage from liver disease). Liver transplantation
can be an effective treatment, particularly for people
with severe liver failure.
The objectives of treatment would
propagation (increase) of thrombosis
the ascites (e.g low sodium diet, diuretics)
further damage to the liver and allow the cells to
Life expectancy and Quality
Fewer than one third of people with
Budd-Chiari syndrome survive for 1 year without prompt
and effective treatment.
The best approach to prevention is to carefully control
the blood disorders that can lead to Budd-Chiari syndrome.
which is now known as Progressive Familial Intrahepatic
Cholestasis (PFIC), is a rare, inherited condition
that mainly affects the liver and bile. Bile is made
within the liver and is essential for the digestion
and absorption of fats. Bile is transported from the
liver to the small intestine through bile ducts.
The average age at onset is 3 months, although some
patients do not develop apparent cholestasis until
later, even as late as adolescence. PFIC can progress
rapidly and cause cirrhosis during infancy, or it
may progress relatively slowly with minimal scarring
well into adolescence.
Children who suffer from PFIC are unable to drain
bile from the liver even though the bile duct appears
to be open and functional. Bile will then build up
in the liver causing damage to liver cells. Over time,
the liver damage can results in cirrhosis and liver
failure. This usually occurs in the first decade of
life and a liver transplant is usually necessary.
PFIC is an extremely rare disease that seems to affect
only children. Both boys and girls seem to be affected
equally. The incidence and prevalence in children
is not known because the disease is very rare. First
described as Byler’s disease, this disease was
thought to only occur in descendants of an Amish man
named Jacob Byler. However, recently more cases have
been reported and thus the change in the name of the
disease to PFIC.
PFIC is a genetic disorder that
is caused by a problem in the genes that code for
the machinery needed to make bile and transport it
from the liver into bile ducts. When this machinery
fails, the liver cannot remove bile from the blood
and eliminate it into the bile ducts.
Bile is used for the excretion of toxins from the
body and also the digestion of fats and vitamins.
This will result in the build up of bile and toxins
in the liver, bloodstream, and other places in the
body like the skin.
A gene for PFIC has been identified and follows the
inheritance pattern of autosomal recessive. Every
person is born with two copies of every gene, one
inherited from each parent. In order to have PFIC,
a child must receive two bad copies of the PFIC gene.
If the child only has one, then he/she will not be
affected but is called a “carrier” for
PFIC (and can pass this gene to their children). If
both parents have one copy of the bad PFIC gene (both
parents are carriers), then there is a 25% chance
that their child will have PFIC, a 50% chance that
the child will be a carrier, and a 25% chance that
the child will have no bad PFIC genes.
PFIC usually occurs soon after birth
(within six months) and is a very rapidly progressing
disease. Sometimes children may not develop the disease
until later in childhood and even into adolescence.
Children with PFIC may exhibit some or all of the
(yellowing of skin and/or eyes) – usually present
soon after birth.
severe itching (pruritis) due to bile build up in
poor weight gain and/or growth (failure to thrive)
enlarged liver and/or enlarged spleen
lack of energy
loss of appetite with nausea and vomiting
foul smelling stools or fatty stools from the inability
to absorp fat in the diet
pale, grey stools – from bile dysfunction
dark urine – excessive bilirubin in the urine.
PFIC is diagnosed by recognition
of the signs of liver dysfunction and through blood
tests. Liver function tests and blood analysis are
performed to assess the liver and biliary system.
Children with PFIC will have high amounts of bile
in their bloodstream. If the blood tests show that
there is a problem with bile drainage, a special picture
of the liver may be taken to see how much bile is
flowing in the liver.
A test called a bile salt screen may be used to confirm
PFIC (PFIC patients have a very high bile salt content).
Another test also used to differentiate between two
types of PFIC is to test for the amount of an enzyme
called gamma-glutamyl-transferase (GGT). A child may
be diagnosed with one type of PFIC (Low-GGT PFIC)
where the amount of GGT is normal or low in the blood,
but bile levels are very high. Another type of PFIC
(High-GGT PFIC) occurs when bile and GGT levels in
the blood are very high. These children seem to have
a more severe and progressive disease. Special DNA
based genetic blood tests can be sent to confirm the
Treatment – Medical,
The treatment of PFIC involves management
of the symptoms of the disease, preventing any further
complications, and surgical intervention. Depending
on the severity of the disease, the primary intervention
is to give medicines that will increase bile flow
and relieve the severe itching due to build up of
bile in the blood and skin. Vitamin supplements are
needed because reduced bile leads to difficulties
in absorption of vitamins A, D, E, and K.
As the disease progresses, surgical intervention
is the only option for patients with PFIC. A procedure
called partial external biliary diversion (PEBD) is
often first attempted to try to reduce the amount
of bile circulating in the liver. This strategy is
used to try to preserve the function of the liver
and reduce liver damage. This surgical technique involves
taking a piece of the intestine and using it as a
channel for bile flow. The piece of intestine forms
a passage form the gallbladder (organ that stores
bile) to the outside of the skin thereby allowing
the excretion of bile and wastes. PEBD is often used
in older patients who are unresponsive to medical
treatments. If the PEBD is unsuccessful or if PFIC
progresses to end-stage liver failure, liver transplantation
is the only curative option.
Life expectancy and Quality
Most PFIC patients will progress
to cirrhosis and will need a liver transplant at some
point in their life. However the survival rates for
liver transplantation are excellent with almost 90%
of patients having successful transplants. There is
a good quality of life after recovery from transplantation
but close monitoring and lifetime immunosuppressive
medications are required.