Budd – Chiari

( Hepatic
Venous
Obstruction)
syndrome By: Dr. Ramy El-Barody
Resident Dr. of Tropical medicine and Gastroenterology, Qena University Hospital
 An Overview
• It’s associated with the names of Budd and Chiari
although Budd ’ s description omitted the features,
and Chiari ’ s paper was not the first to report the
clinical picture.
• Budd–Chiari syndrome (BCS) results from
obstruction to hepatic venous outflow and may be
caused by either thrombotic or nonthrombotic
occlusion.
• It occurs in 1/100 000 of the general population.
• A similar syndrome may be produced by
constrictive pericarditis or right heart failure.
• The syndrome comprises :
- Hepatomegaly
- Abdominal pain
- Ascites
• Hepatic Histology shows zone 3 sinusoidal
distension and pooling.
CLASSIFICATION
A. The duration of symptoms and signs of
liver disease
• Acute
• Subacute
• Chronic
B. The site of obstruction
• Small hepatic veins, excluding terminal
venules
• Large hepatic veins
• Hepatic inferior vena cava(IVC)
C. The cause of obstruction
• Membranous web
• Direct infiltration by tumor or metastasis along
veins
• Thrombosis
 Etiology and Pathogenesis
• Most patients with BCS present within 3 months of the onset of
symptoms.
• Subacute or chronic disease mostly at the time of presentation,
a finding suggesting that thrombosis of intrahepatic veins leads
subsequently to occlusion of large collecting veins.
• Membranous occlusion of the hepatic veins (MOHV) is a
common cause of BCS in Asia.
The pathogenesis is controversy; many have assumed that
webs are congenital, but the onset of symptoms in the fourth
decade of life and the pathologic features are more suggestive
of a post-thrombotic event.
• Most patients with BCS have an underlying Thrombotic
diathesis.In less than 20% of cases the disorder is Idiopathic
Disorders associated with BCS include the following:
1. Hematologic disorders
• Myeloproliferative disorders particularly Polycythemia Rubra Vera in up to 50%
od cases, often young females, multiple thrombotic conditions may be found
• Paroxysmal nocturnal hemoglobinuria (PNH) in up to 35% of cases may be
associated with BCS, with varying severity
• Systemic Lupus, e’ circulating lupus anticoagulants sometimes with DIC
• Antiphospholipid syndrome either 1ry or 2ry to SLE
• Disseminated intravascular coagulation (DIC)
• Idiopathic granulomatous venulitis
2. Inherited thrombotic diathesis
• Factor V Leiden mutation
• Protein C deficiency
• Protein S deficiency (rare)
• Prothrombin gene mutation (G20210A)
• Antithrombin III deficiency (rare), whatever 1ry or 2ry to proteinuria
3. Pregnancy or high-dose estrogen (oral contraceptives )
 4. Chronic infections of the liver
• Aspergillosis
• Amebic abscess
• Hydatid cysts
• Tuberculosis
• Severe polycystic Liver disease, may mechanically compress hepatic veins
 5. Tumors
• Hepatocellular carcinoma
• Adrenal or Renal cell carcinoma
• Angiosarcoma
 6. Chronic inflammatory diseases
• Behçet’s disease, hepatic vein thrombosois usualy a sudden event, related to
extension of a caval thrombosis to the osteum of hepatic veins
• Inflammatory bowel disease
• Sarcoidosis
 7. Central hepatic vein involvement in the alcoholic and in veno – occlusive disease
 8. Myxoma of the right atrium and metastases to the right atrium
 9. Liver transplantation may be followed by small hepatic vein stenosis with some of
the features of veno - occlusive disease.
 Pathological changes
• The hepatic veins show occlusion at points
from the ostia to the smaller radicles.
• Thrombus may be purulent or may contain
malignant cells, depending on the cause.
• Involvement of large hepatic veins is usually
thrombotic. Isolated obstruction to the
inferior vena cava or small hepatic veins is
usually non – thrombotic.
• The Liver is
- Enlarged, purplish and smooth.
- Venous congestion is gross and the cut surface shows ‘
nutmeg ’ change.
- Hepatic veins proximal to the obstruction and, in the acute
stage, subcapsular lymphatics, are dilated and prominent.
• In chronic cases
- The vein wall is thickened and there may be some
recanalization. In others it’s replaced by a fibrous strand, a
fibrous web may be seen
- The caudate lobe is enlarged and compresses the IVC.
- The fibrosis and regenerative nodules continue to evolve
after the first hepatic vein thrombosis and often progress to
involve the portal venous system.
Vertical section of the liver at
autopsy in hepatic
venous obstruction. The pale
areas represent regeneration
and the dark areas are
congested. Note the marked
hypertrophy of the caudate
lobe (C).
 Histology shows:
• Zone 3 venous dilatation with hemorrhage and
necrosis
• Persisting hepatic venous obstruction results in
venocentric cirrhosis, so - called reverse
lobulation. Portal vein involvement leads to
venoportal cirrhosis and mixed forms exist.
• Large regenerative nodules are usual and are
related to a new arterial supply
• Nodular regenerative hyperplasia is frequent
with long standing arterialization
Longitudinal section of hepatic venules showing fibrosis in
the lumen, thickening of the wall and surrounding loss of
hepatocytes. (Chromophobe aniline blue.)
 Clinical features
• These depend on the speed of occlusion, severity of liver
dysfunction, anatomical sites of thrombosis and etiology.
• The picture varies from a fulminant course, to a
presentation as chronic hepatocellular disease.
• The classic triad of hepatomegaly, ascites, and
abdominal pain is seen in most patients but is
nonspecific.
o Splenomegaly may develop in almost half of patients.
o Peripheral edema suggests the possibility of thrombosis
or compression of the IVC.
o Jaundice is rare.
• In the most Acute form (often suffering from
some other condition):
- Abdominal pain, vomiting, liver
enlargement, ascites and mild icterus.
Watery diarrhoea, following MVO, is a
terminal, inconstant feature.
- If the hepatic venous occlusion is total,
delirium and coma with hepatocellular failure
and death occurs within a few days.
• In the more usual Chronic form:
- Pain over an enlarged tender liver, ascites,
Jaundice is mild or absent. Pressure over the
liver may fail to fill the jugular vein (negative
hepatojugular reflux )
- As portal hypertension increases, the spleen
becomes palpable.
-The enlarged caudate lobe, palpable in the
epigastrium, may simulate a tumour
• Asymptomatic patients, who account for up to
15% of cases may be discovered incidentally.
• If the inferior vena cava is blocked, oedema of
the legs is gross and veins distend over the
abdomen, flanks and back. Albuminuria is
found.
• The condition may develop over months as
ascites and wasting.
 DIAGNOSIS
 Routine biochemical and hematologic parameters

o Of Little value in differential diagnosis

o Abnormal but nonspecific
o No distinctive pattern of abnormalities
• Serum transaminase values increase and, if very high,
concomitant blockage of the PV is suggested
• Serum alkaline phosphatase level is raised
• Serum bilirubin rarely exceeds 2 mg/100 mL
• Albumin value reduced
• The Prothrombin time is markedly increased, especially in
the acute type
 Ascitic fluid characteristics are useful clues to the diagnosis:
• High protein concentration (greater than 25g/L) but this is not
always so.
• White blood cell count usually lower than 500/mm3
• Serum-ascites albumin gradient usually 1.1 or higher

 Hepatic venous outflow obstruction is classified according to

the site of obstruction and the presence or absence of portal vein
thrombosis to:
(1) Hepatic vein thrombosis or obstruction without obstruction or
compression of the (IVC)
(2) Hepatic vein thrombosis or obstruction with IVC obstruction
(3) Isolated Hepatic vein webs
(4) Isolated IVC webs
 Early diagnosis depends on Doppler ultrasound and MRI
 Ultrasound shows
- Hepatic vein abnormalities, caudate lobe hypertrophy,
increased reflectivity and compression of the IVC.
- The appearances are hypoechogenic in the early stages of
acute thrombosis and hyperechogenic with fibrosis in the
later stages.
- Ascites is confirmed.
 Doppler ultrasound shows
- Abnormalities in the direction of flow in the hepatic vein
and retro hepatic IVC.
- The blood flow in the IVC and hepatic veins may be
absent, reversed, turbulent or continuous.
 CT scan shows
- Enlargement of the liver with diffuse hypodensity before
and patchy enhancement after contrast. Heterogeneous
hepatic parenchymal patterns are related to regional
differences in portal flow.
- Thrombi in the IVC and/or hepatic vein may be seen as
intraluminal filling defects that are not changed by
contrast
 MRI shows
- Absence of normal hepatic venous drainage into the IVC,
collateral hepatic veins and signal intensity alterations in
the hepatic parenchyma.
- The caudate lobe can be seen deforming the IVC.
CT scan (unenhanced)showing the caudate lobe (arrow)
with surrounding underperfused parenchyma.
MRI showing a liver (L) which is dyshomogeneous, the
aorta (A) and the IVC (V). The side - to - side narrowing of
the IVC (arrows) is due to the enlarged caudate lobe.
 In Needle Liver Biopsy speckled zone 3 areas can be
distinguished from the pale portal areas. Histologically, the
picture is of zone 3 congestion.
 Hepatic venography may fail or show narrow occluded
hepatic veins. Adjacent veins show a tortuous, lace – like
spider - web pattern.
 Inferior vena cavography establishes the patency of the
IVC. The hepatic segment may show side - to - side
narrowing due to distortion from the enlarged caudate lobe.
 From selective coeliac arteriography the hepatic artery
appears small. Branches appear stretched and displaced,
producing the appearance of multiple space – occupying
lesions simulating metastases. The venous phase shows
delayed emptying of the portal venous bed.
 Inferior vena cavogram. AP view showing
side -to-side narrowing & distortion of
Hepatic venogram. Note the lace - like
IVC (arrows). Extrinsic compression from
spider - web pattern.
left is due to an enlarged caudate lobe.
 The Diagnostic approach to a patient
suspected of having hepatic vein occlusion
should :
• Begin with Color Doppler ultrasonography,
followed by three-phase CT or MRI.
• If imaging is equivocal for BCS, then hepatic
venography with inferior vena cavography
should be performed to confirm the diagnosis.
• Liver biopsy may be of value to define the
extent of fibrosis but is usually unnecessary
 Prognosis
• In symptomatic untreated patients, 90% will die by 3
years.
• With treatment survival has reached 75% at 5 years.
• Severity of liver and renal dysfunction are important as
predictors of survival
• Hepatocellular carcinoma develops in about 10%,
during a mean follow - up of 5 years.
• The fulminant form is usually fatal unless liver
transplantation is carried out.
• Variceal haemorrhage can occur, as well as extension
of the thrombus.
 Treatment
 Early treatment of an underlying haematological
disorder improves long - term survival.
 Long - term anticoagulation is given for all
patients irrespective of whether a thrombophilic
condition is diagnosed.
 Ascites is treated with a low sodium diet,
diuretics and paracentesis. Severe cases demand
ever increasing doses of potent diuretics and
eventually the patient is overtaken by inanition
and renal failure, unless a TIPS is placed.
 Percutaneous Transluminal Angioplasty
• This has been used to dilate webs and also for
hepatic vein obstruction after liver transplant.
• As for hepatic vein webs, multiple dilatations
are usually necessary.
• Intravascular metallic stents may be
introduced after the dilatation (mostly in those
in whom angioplasty has failed.
• Together with anticoagulation this treats BCS
in up to 30% of cases
 Transjugular intrahepatic stent shunt
• If anticoagulation and percutaneous angioplasty, if
performed, fail, TIPS is the next step.
• The aim is to decompress the liver and reverse portal
venous flow.
• Survival at 5 years is currently 70% or more.
• If the hepatic vein cannot be entered a transcaval
approach is used, and even if the portal vein is
occluded a TIPS placement is possible
• Long - term patency (with anticoagulation) should be
improved by PTFE - covered stents
 Surgical portal – systemic shunts
• Surgical shunts are indicated only if TIPS is not available or
can't be fashioned, and transplantation isn’t feasible
• It should be avoided in acute Budd – Chiari syndrome as
liver failure may be precipitated.
• Results on the whole are unsatisfactory due to thrombosis
of the shunt, especially in those with haematological
disorders or where stents have been used
• If the shunt remains patent, 5 - year survival is 87%, falling
to 38% if the shunt thromboses.
• No survival benefit has been clearly shown when taking
into account the initial severity of disease.
Liver transplantation
• This is indicated when the patient deteriorates
despite aggressive medical and radiological
therapy.
• The 1 – year survival is 85% and 5 year survival of
80% .
• Post - transplant thrombosis remains a problem
and early anticoagulation is essential.
• After transplantation, obstruction to hepatic
venous drainage can be improved by balloon
angioplasty.
A Conclusion on BCS
 o n
bst ucti
r
i d al O
us o o m e
Si n Syn dr
 An Overview
• Sinusoidal obstruction syndrome (SOS) was originally
described by Chiari in 1899, and was further described as
hepatic vein endophlebitis by Bras in 1954.
• SOS (formerly referred to as veno-occlusive disease) is
most often seen In:
- Acute form following bone marrow transplantation
(BMT) or hematopoietic stem cell transplantation.
- Chronic form following toxicity of pyrrolizidine alkaloids
from plants of the Crotalaria, Senecio, and Heliotropium
genera. They are ingested in the form of herbal teas,
hence the term Jamaican bush tea disease.
• Histologic features include the following:
- Subendothelial sclerosis of terminal hepatic
venules
- Thrombosis secondary to sclerosis
- Sinusoidal fibrosis, particularly in later stages
and with chronic injury
• No single histologic feature is pathognomonic.
A correlation exists between the number of
histologic abnormalities and the clinical
severity of SOS.
 PATHOGENESIS

• Cytoreductive therapy is toxic primarily to endothelial cells,

both sinusoidal and vascular. These cells are more susceptible
to glutathione depletion in response to various agents,
including dacarbazine, azathioprine, and monocrotaline.
• Various cytokines including tumor necrosis factor alpha (TNF-
α) are released in response to cytoreductive therapy. Patients
with hepatic failure and multiorgan failure syndrome have
been shown to have high circulating levels of TNF-α and other
cytokines.
- TNF in particular exerts procoagulant effects on protein C and
may be involved in the pathogenesis of thrombosis in SOS;
however, much of the pathophysiology is speculative at
present.
 Diagnosis

 SOS following BMT has been defined as the occurrence

of two or more of the following characteristics appearing
within 20 days after transplantation:
• Painful hepatomegaly
• Sudden weight gain of more than 2% of baseline body
weight
• Total serum bilirubin level greater than 2.0 mg/dL
 The occurrence of SOS is significantly correlated with the
subsequent development of renal insufficiency, pleural
effusions, heart failure, pulmonary infiltrates, and
bleeding requiring blood transfusions
 The more Chronic form of SOS develops in persons
who ingest pyrrolizidine alkaloids.
• Clinical features of this condition are similar to those
of hepatic vein occlusion and include:
Tender hepatomegaly, abdominal pain, ascites, and
fatigue.
• The absence of specific features and the lack of
noninvasive methods for detecting this condition
make diagnosis difficult
• Liver biopsy specimens usually show sinusoidal and
perivenular fibrosis, as well as subendothelial
sclerosis.
 CT Scan :
• May be helpful in distinguishing (SOS) from graft-
versus-host (GVH) disease :
– Patients with SOS have periportal edema, ascites,
and a narrow right hepatic vein, whereas
– Those with GVH disease often have thickening of
the small bowel.
• Using clinical definitions, up to 50% of patients
with BMT develop SOS. The mortality rate for all
patients with clinical evidence of SOS is 30%-40%
RISK FACTORS FOR ACUTE SOS FOLLOWING BMT OR HSCT

• Pretransplant elevation in serum (AST) or (ALT) levels

• Past history of viral or drug-induced hepatitis
• Past history of abdominal radiation
• Older or very young (less than 6.5 years) recipient age
• Poor pretransplant performance status and reduced
pulmonary diffusion capacity
 More intensive myeloablative cytoreductive regimens are
associated with an increased frequency of SOS:
• Radiation dose greater than 12 Gy
• Cyclophosphamide plus busulfan
• Cyclophosphamide, carmustine (BCNU), and etoposide
 TREATMENT
 Treatment of SOS following BMT is largely Supportive:
• Support with Platelet and Red blood cell Transfusions is
often necessary because of the profound cytopenias that
accompany BMT.
• Use of Dopamine and other pressors is often necessary
to maintain renal perfusion, particularly in the presence
of a capillary leak syndrome.
• Broad-spectrum Antibiotics are used to treat
presumptive infection
o Excessive fluid administration, which results in worsening
of cardiac and pulmonary function, should be Avoided.
• Defibrotide, a polydisperse mixture of single-stranded
oligonucleotide, may be of benefit in treating severe SOS,
with a complete remission rate of 30% to 60%.
• Antithrombin may be of benefit in preventing progression
of SOS if given early in the course of the illness.
• Prostaglandin E, Ursodeoxycholic acid, Pentoxifylline, and
Heparin all have had limited success in preventing SOS.
• TIPS is technically feasible and has been of benefit in a
small number of patients with SOS.
 Treatment of Chronic SOS often requires Liver
Transplantation because of the extensive fibrosis that is
usually present at the time of diagnosis. Early cases may be
managed with a Portosystemic Shunt.
 YO U
A NK
TH