Budd Chiari Syndrome

Author: Praveen K Roy, MD, AGAF; Chief Editor: Julian Katz, MD more...

Updated: Aug 18, 2011 Background

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, and infections.

Pathophysiology
Obstruction of intrahepatic veins leads to congestive hepatopathy. This results from
obstruction of 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.[1, 2]

Epidemiology
Frequency

United States
Budd-Chiari syndrome is rare, but the exact frequency is unknown.

International
Internationally, Budd-Chiari syndrome is also rare, but the exact frequency is unknown.
Membranous webs are a common cause of Budd-Chiari syndrome in Asian countries.

Mortality/Morbidity
Budd-Chiari syndrome is a potentially fatal disorder, if untreated.

Race
The syndrome occurs in persons of all races.

Sex
The syndrome is equally present in both sexes. Emergent presentation is more common in
women than in men.

Age
Age at presentation is usually the third or fourth decade of life, although the condition
may also occur in children or elderly persons.

History
The classic triad of abdominal pain, ascites, and hepatomegaly is observed in the vast
majority of patients but is nonspecific. A high index of suspicion is needed to make the
diagnosis.
Four main clinical variants have been described: acute liver disease, subacute liver
disease, fulminant liver disease, and liver failure. The most common presentation is
subacute liver disease complicated by portal hypertension and varying degrees of liver
decompensation.[1, 2, 3]

Acute and subacute form: These forms are characterized by rapid development of
abdominal pain, ascites, hepatomegaly, jaundice, and renal failure.
Chronic form: This form of presentation is the most common. Patients present
with progressive ascites. Jaundice is absent, and approximately 50% of patients
also have renal impairment.
Fulminant form: This form of presentation is uncommon. Fulminant or
subfulminant hepatic failure is present along with ascites, tender hepatomegaly,
jaundice, and renal failure.

Physical
Physical examination may reveal the following findings:

Icterus
Ascites
Hepatomegaly
Splenomegaly
Ankle edema
Stasis ulcerations
Prominence of collateral veins

Causes
Most patients have an underlying thrombotic diathesis. In approximately one third of
patients, an underlying cause is not evident.
The causes of Budd-Chiari syndrome are as follows:

Hematological disorders
o Polycythemia rubra vera
o Paroxysmal nocturnal hemoglobinuria
o Unspecified myeloproliferative disorder
o Antiphospholipid antibody syndrome
o Essential thrombocytosis
Inherited thrombotic diathesis
o Protein C deficiency
o Protein S deficiency
o Antithrombin III deficiency
o Factor V Leiden deficiency
Pregnancy and postpartum[4]
Membranous webs
Oral contraceptives
Chronic infections
o Hydatid cysts
o Aspergillosis
o Amebic abscess
o Syphilis
o Tuberculosis
Chronic inflammatory diseases
o Behet disease
o Inflammatory bowel disease
o Sarcoidosis
o Systemic lupus erythematosus
o Sjgren syndrome
o Mixed connective-tissue disease
Tumors
o Hepatocellular carcinoma[5]
o Renal cell carcinoma
o Leiomyosarcoma
o Adrenal carcinoma
o Wilms tumor
o Right atrial myxoma
Miscellaneous
o Alpha1-antitrypsin deficiency
o Trauma
o Dacarbazine

Urethane
Idiopathic
o

Differential Diagnoses

Pericarditis, Constrictive

Laboratory Studies

Examination of ascitic fluid provides useful clues to the diagnosis.

o Patients usually have high protein concentrations (>2 g/dL). This may not
be present in persons with the acute form of Budd-Chiari syndrome.
o The WBC count is usually less than 500/L.
o The serum ascitesalbumin gradient is usually less than 1.1 (except in the
acute forms of the disease).
Routine biochemical test results are usually nonspecific. Mild elevations in serum
aminotransferase and alkaline phosphatase levels are present in 25-50% of
patients.
Hematological studies should be performed to evaluate for a hypercoagulable
state.
See Polycythemia Vera; Thrombocytosis, Essential; Protein C Deficiency; Protein
S Deficiency; and Myeloproliferative Disease for more information.

Imaging Studies

Ultrasonography
o Thrombi can be visualized.
o Color-flow Doppler ultrasonography is the preferred mode. Sensitivity and
specificity are 85-90%.[6, 7]
Magnetic resonance imaging (MRI) scanning with pulsed sequencing
o MRI images help in the assessment of hepatic venous blood flow.
o Sensitivity and specificity are 90%.
Hepatic venography
o Thrombi are observed in hepatic veins.
o With venography, hepatic vein orifices cannot be cannulated.[8]

Procedures

Liver biopsy

Histologic Findings
Pathological findings after liver biopsy are (1) high-grade venous congestion and
centrilobular liver cell atrophy, and, possibly, (2) thrombi within the terminal hepatic
venules. The extent of fibrosis can be determined based on biopsy findings.

Medical Care
Medical therapy can be instituted for short-term, symptomatic benefit.[9] Medical therapy
alone is associated with a high 2-year mortality rate (80-85%).

Management of ascites: See Ascites for more information.

Anticoagulation
Antithrombolytic therapy: This therapy has been used in a few cases. Agents
include streptokinase, urokinase, recombinant tissue plasminogen activator, and
other modalities.
Angioplasty: This can help relieve obstruction caused by membranous webs.
In a study of 101 patients with Budd-Chiari syndrome, Li et al concluded that the
condition can be safely and effectively treated with percutaneous transhepatic
balloon angioplasty (PTBA).[10] The authors reported successful PTBA (performed
after hepatovenography and with or without stenting) in 92 of the studys patients,
with all of the successful procedures resulting in significant symptom
improvement.
Complications reported in the above study, all of which were managed
nonsurgically, included acute hepatic vein thrombosis, occurring during or after
the operation (3 patients); sustained intraperitoneal bleeding from the transhepatic
puncture track (2 patients); pulmonary embolism, which occurred during the
procedure (1 patient); and intrahepatic hematoma (1 patient). Primary patency
rates at 6-, 12-, and 24-month follow-up were 84%, 78%, and 76%, respectively
(although a number of patients did not return for follow-up). Secondary patency
rates for these same follow-up periods were 95%, 92%, and 84%, respectively.
Despite these satisfactory midterm patient outcomes, the authors cautioned that
long-term outcomes in patients treated with PTBA for Budd-Chiari syndrome
require investigation.

Surgical Care
Decompression of the hepatic vasculature should be offered if portal hypertension is the
cause of the symptoms.
Either surgery or a transjugular intrahepatic portosystemic shunt procedure can be
performed.[2, 11, 12, 13, 14, 15]
Liver transplantation should be offered if decompensated liver cirrhosis is present.[16]

Consultations

Gastroenterologist
Hematologist
Surgeon
Radiologist[17, 18]

Diet
A low-sodium diet is recommended for the control of ascites.

Medication Summary
Anticoagulation is needed in some patients, especially those with underlying
hematological disorders as the cause of the syndrome.

Anticoagulants
Class Summary
Prevent recurrent or ongoing thromboembolic occlusion.
View full drug information

Warfarin (Coumadin)
Interferes with hepatic synthesis of vitamin Kdependent coagulation factors. Used for
prophylaxis and treatment of venous thrombosis, pulmonary embolism, and
thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3.

Fibrinolytic agents
Class Summary
Used to dissolve a pathologic intraluminal thrombus or embolus that has not been
dissolved by the endogenous fibrinolytic system. Also used for the prevention of
recurrent thrombus formation and for the rapid restoration of hemodynamic disturbances.
View full drug information

Streptokinase (Kabikinase, Streptase)

Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots,
fibrinogen, and other plasma proteins. Increase in fibrinolytic activity that degrades
fibrinogen levels for 24-36 h occurs with intravenous infusion.
View full drug information

Urokinase (Abbokinase)

Direct plasminogen activator that acts on the endogenous fibrinolytic system and
converts plasminogen to the enzyme plasmin, which, in turn, degrades fibrin clots,
fibrinogen, and other plasma proteins. Most often used for local fibrinolysis of
thrombosed catheters and superficial vessels. Advantage is that agent is nonantigenic.
However, more expensive than streptokinase and thus limits use. When used for local
fibrinolysis, urokinase is given as local infusion directly into area of thrombus and with
no bolus given. Dose should be adjusted to achieve clot lysis or patency of affected
vessel.
View full drug information

Alteplase (Activase)
Tissue plasminogen activator used in management of acute myocardial infarction, acute
ischemic stroke, and pulmonary embolism. Safety and efficacy with concomitant
administration of heparin or aspirin during first 24 h after symptom onset have not been
investigated.

Further Inpatient Care

Gastroscopy should be performed to help rule out the presence of esophageal and
gastric varices. If present, they may be obliterated with banding or sclerotherapy.
Nonselective beta-blockers (eg, propranolol, nadolol) can be administered for
primary prophylaxis against variceal bleeding.
Electrolyte levels should be monitored closely because diuretics and other factors
can cause electrolyte imbalances.
Prothrombin time and activated partial thromboplastin time should be monitored
once anticoagulation is started. They should be maintained within the therapeutic
range.

Further Outpatient Care

Long-term anticoagulation is often needed, and it may also be needed after liver
transplantation.

Transfer

Once a patient is determined to be a transplant candidate, transfer to a liver

transplant unit.

Complications

Complications secondary to hepatic decompensation

Hepatic encephalopathy
Variceal hemorrhage
Hepatorenal syndrome
Portal hypertension

Complications secondary to hypercoagulable state

Prognosis

The natural history is not well known. The following factors have been associated
with a good prognosis:
o Younger age at diagnosis
o Low Child-Pugh score
o Absence of ascites or easily controlled ascites
o Low serum creatinine level
A formula to calculate the prognostic index has been proposed. A score of less
than 5.4 is associated with a good prognosis. The formula to calculate the
prognostic index is as follows:

Prognostic index = (ascites score X 0.75) + (Pugh score X 0.28) + (age X 0.037) +
(creatinine level X 0.0036)

The prognosis is poor in patients with Budd-Chiari syndrome who remain

untreated. Death results from progressive liver failure in 3 months to 3 years from
the time of diagnosis.
The 5-year survival rate is 38-87% following portosystemic shunting. The
actuarial 5-year survival rate following liver transplantation is 70%.[15]

NEW TOPIC

BuddChiari syndrome
Budd-Chiari syndrome

Budd-Chiari syndrome secondary to cancer, note clot

in the inferior vena cava and the metastasis in the liver

BuddChiari syndrome is the clinical picture caused by occlusion of the hepatic veins.
It presents with the classical triad of abdominal pain, ascites and hepatomegaly.
Examples of occlusion include thrombosis of hepatic veins. The syndrome can be
fulminant, acute, chronic, or asymptomatic.

Signs and symptoms

The acute syndrome presents with rapidly progressive severe upper abdominal pain,
jaundice, hepatomegaly (enlarged liver), ascites, elevated liver enzymes, and eventually
encephalopathy. The fulminant syndrome presents early with encephalopathy and ascites.
Severe hepatic necrosis and lactic acidosis may be present as well. Caudate lobe
hypertrophy is often present. The majority of patients have a slower-onset form of Budd
Chiari syndrome. This can be painless. A system of venous collaterals may form around
the occlusion which may be seen on imaging as a "spider's web." Patients may progress
to cirrhosis and show the signs of liver failure.
On the other hand, incidental finding of a silent, asymptomatic form may not be a cause
for concern.

Causes

The cause cannot be found in about half of the patients

Primary (75%): thrombosis of the hepatic vein
Secondary (25%): compression of the hepatic vein by an outside structure (e.g. a
tumor)
Hepatic vein thrombosis is associated with the following in decreasing order of
frequency:
a) Polycythemia vera
b) pregnancy
c) post partum state
d) use of oral contraceptive
e) paroxysmal nocturnal hemoglobinuria
f) Hepatocellular carcinoma
Infection such as tuberculosis
Congenital venous webs
Occasionally inferior vena caval stenosis

Often, the patient is known to have a tendency towards thrombosis, although Budd
Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic
tendencies include Protein C deficiency, Protein S deficiency, the Factor V Leiden

mutation, Hereditary anti-thrombin deficiency and Prothrombin Mutation G20210A.[1] An

important non-genetic risk factor is the use of estrogen-containing (combined) forms of
hormonal contraception. Other risk factors include the antiphospholipid syndrome,
aspergillosis, Behet's disease, dacarbazine, pregnancy, and trauma.
Many patients have BuddChiari syndrome as a complication of polycythemia vera
(myeloproliferative disease of red blood cells).[2] Patients suffering from paroxysmal
nocturnal hemoglobinuria (PNH) appear to be especially at risk for BuddChiari
syndrome, more than other forms of thrombophilia: up to 39% develop venous
thromboses [3] and 12% may acquire Budd-Chiari.[4]
A related condition is veno-occlusive disease, which occurs in recipients of bone marrow
transplants as a complication of their medication. Although its mechanism is similar, it is
not considered a form of BuddChiari syndrome.
Other toxicologic causes of veno-occlusive disease include plant & herbal sources of
pyrrolizidine alkaloids such as Borage, Boneset, Coltsfoot, T'u-san-chi, Comfrey,
Heliotrope (sunflower seeds), Gordolobo, Germander, and Chaparral.

Pathophysiology

Posterior abdominal wall, after removal of the peritoneum, showing kidneys, suprarenal
capsules, and great vessels. (Hepatic veins labeled at center top.)
Any obstruction of the venous vasculature of the liver is referred to as BuddChiari
syndrome, from the venules to the right atrium. This leads to increased portal vein and
hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure
causes: 1) increased filtration of vascular fluid with the formation of ascites in the
abdomen; and 2) collateral venous flow through alternative veins leading to esophageal,
gastric and rectal varices. Obstruction also causes centrilobular necrosis and peripheral
lobule fatty change due to ischemia. If this condition persists chronically what is known
as Nutmeg liver will develop. Renal failure may occur, perhaps due to the body sensing

an "underfill" state and subsequent activation of the renin-angiotensin pathways and

excess sodium retention.

Diagnosis
When BuddChiari syndrome is suspected, measurements are made of liver enzyme
levels and other organ markers (creatinine, urea, electrolytes, LDH).
BuddChiari syndrome is most commonly diagnosed using ultrasound studies of the
abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins,
thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord
replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging
(MRI) is sometimes employed although these methods are generally not as sensitive.
Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd
Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or
Reye's syndrome.

Treatment
A minority of patients can be treated medically with sodium restriction, diuretics to
control ascites, anticoagulants such as heparin and warfarin, and general symptomatic
management. The majority of patients require further intervention. Milder forms of BuddChiari may be treated with surgical shunts to divert blood flow around the obstruction or
the liver itself. Shunts must be placed early after diagnosis for best results.[5] The
transjugular intrahepatic portosystemic shunt is similar to a surgical shunt: it
accomplishes the same goal but has a lower procedure-related mortalitya factor which
has led to a growth in its popularity. Patients with stenosis or vena caval obstruction may
benefit from angioplasty.[6] Limited studies on thrombolysis with direct infusion of
urokinase and tissue plasminogen activator into the obstructed vein have shown moderate
success in treating BuddChiari syndrome; however, it is not routinely attempted.
Liver transplantation is an effective treatment for Budd-Chiari. It is generally reserved for
patients with fulminant hepatic failure, failure of shunts, or progression of cirrhosis that
reduces the life expectancy to 1 year.[7] Long-term survival after transplantation ranges
from 69-87%. The most common complications of transplant include rejection, arterial or
venous thromboses, and bleeding due to anticoagulation. Up to 10% of patients may have
a recurrence of BuddChiari syndrome after the transplant.

Prognosis
Several studies have attempted to predict the survival of patients with BuddChiari
syndrome. In general, nearly 2/3 of patients with Budd-Chiari are alive at 10 years. [5]
Important negative prognostic indicators include ascites, encephalopathy, elevated ChildPugh scores, elevated prothrombin time, and altered serum levels of various substances
(sodium, creatinine, albumin, and bilirubin). Survival is also highly dependent on the
underlying cause of the BuddChiari syndrome. For example, a patient with an

underlying myeloproliferative disorder may progress to acute leukemia, independently of

BuddChiari syndrome.

Eponym
It is named after George Budd,[8][9] a British physician, and Hans Chiari.,[10] an Austrian
pathologist.

External links

Budd-Chiari Syndrome at Merck Manual of Diagnosis and Therapy Home Edition

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