Budd-Chiari Syndrome and Other Vascular Disorders

Key Points

1
Hepatic vein occlusion, or Budd-Chiari syndrome (BCS), is an uncommon disorder characterized by hepatomegaly, ascites, and abdominal pain. The disorder most often occurs in patients with an underlying thrombotic diathesis including polycythemia vera, factor V Leiden mutation, protein C deficiency, antithrombin deficiency, paroxysmal nocturnal hemoglobinuria, tumors, and chronic inflammatory diseases.
2
The diagnosis is confirmed by visualization of thrombus or absent flow in hepatic veins by Doppler ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI).
3
BCS can be fatal without treatment. The approach to treatment should be stepwise beginning with anticoagulation, followed by angioplasty or transjugular intrahepatic portosystemic shunt (TIPS) placement for portal decompression. Liver transplantation (LT) should be reserved for patients with advanced disease who fail other treatments. Five-year survival rates are 85% to 90%.
4
Portal vein thrombosis (PVT) occurs in patients with an underlying thrombotic disorder, intraabdominal inflammation, injury to the portal vessels, or cirrhosis. Extension of hepatocellular carcinoma (HCC) into the portal vein can also result in thrombosis. In the acute phase, anticoagulation is recommended. Band ligation of varices and beta receptor antagonists are used to prevent variceal bleeding in patients with chronic PVT. TIPS may improve the rate of recanalization in patients with PVT who are awaiting transplantation.
5
Sinusoidal obstruction syndrome (SOS), previously known as venoocclusive disease, is an occlusive disorder of the small hepatic venules and is clinically similar to BCS. It develops as a result of toxic injury to the endothelial cells primarily in patients receiving cytoreductive therapy for allogeneic or autologous hematopoietic stem cell transplantation (HSCT). Unexpected weight gain and development of ascites are the hallmarks of SOS in this setting. Chronic hepatitis C infection appears to increase the risk of SOS. Treatment of mild-to-moderate SOS is largely supportive, but trials have suggested that defibrotide may improve survival in patients with severe SOS and multiorgan failure syndrome.

Budd-Chiari Syndrome

BCS results from obstruction to hepatic venous outflow and may result from either thrombotic or nonthrombotic occlusion.

Classification and Etiology

1.
BSC is classified according to
- a.
  Duration of symptoms and signs of liver disease
  - ▪
    Acute: Development of intractable ascites, abdominal pain, and hepatomegaly within 1 month
  - ▪
    Subacute: Insidious onset over 1 to 3 months with minimal to moderate ascites and evidence of collateral vessels around the hepatic veins
  - ▪
    Chronic: Typically discovered during evaluation of portal hypertension in patients without previous symptoms; progresses to congestive cirrhosis
- b.
  Site of obstruction
  - ▪
    Small hepatic veins, excluding terminal venules
  - ▪
    Large hepatic veins
  - ▪
    Hepatic inferior vena cava (IVC)
- c.
  Cause of obstruction
  - ▪
    Membranous webs
  - ▪
    Direct infiltration by tumor or metastasis along veins
  - ▪
    Thrombosis
2.
The majority of patients with BCS present within 3 months of the onset of symptoms. Most have subacute or chronic disease at the time of presentation, suggesting that thrombosis of intrahepatic veins leads subsequently to occlusion of large collecting veins.
3.
Membranous occlusion of the hepatic veins (MOHV) is a common cause of BCS in Asia but is rarely seen in the United States. The pathogenesis is the subject of controversy; many investigators have assumed that the webs are congenital, but the onset of symptoms in the fourth decade of life and the pathologic features are more suggestive of a postthrombotic event that may represent a complication of chronic BCS.
4.
The majority of patients with BCS have an underlying thrombotic diathesis. The disorder is idiopathic in <20% of cases. Disorders associated with BCS include the following:
- a.
  Hematologic disorders
  - ▪
    Polycythemia rubra vera
  - ▪
    Janus kinase 2 ( JAK2 ) V617F gene mutation-associated myeloproliferative disorder
  - ▪
    Paroxysmal nocturnal hemoglobinuria
  - ▪
    Antiphospholipid antibody syndrome
- b.
  Inherited thrombotic diathesis
  - ▪
    Factor V Leiden mutation
  - ▪
    Protein C deficiency
  - ▪
    Prothrombin gene mutation (G20210A)
  - ▪
    Protein S deficiency (rare)
  - ▪
    Antithrombin deficiency (rare)
  - ▪
    C677T methylenetetrahydrofolate reductase (MTHFR) mutation
- c.
  Pregnancy or high-dose estrogen use (oral contraceptives)
- d.
  Chronic infections of the liver
  - ▪
    Amebic abscess
  - ▪
    Aspergillosis
  - ▪
    Hydatid cysts
  - ▪
    Tuberculosis
- e.
  Tumors
  - ▪
    HCC
  - ▪
    Renal cell carcinoma
  - ▪
    Leiomyosarcoma
- f.
  Chronic inflammatory diseases
  - ▪
    Behçet’s disease
  - ▪
    Inflammatory bowel disease
  - ▪
    Sarcoidosis

Clinical and Laboratory Features

1.
The classic triad of hepatomegaly, ascites, and abdominal pain is seen in the majority of patients but is nonspecific.
- ▪
  Splenomegaly may develop in almost one half of patients.
- ▪
  Peripheral edema suggests the possibility of thrombosis or compression of the IVC.
- ▪
  Jaundice is rare.
2.
Persons with an acute presentation may progress rapidly and require urgent treatment, whereas those with a more insidious onset appear to progress slowly in developing complications of portal hypertension.
3.
Routine biochemical and hematologic parameters
- ▪
  Little value in differential diagnosis
- ▪
  Abnormal but nonspecific
- ▪
  No distinctive pattern of abnormalities
4.
Ascitic fluid characteristics are useful clues to diagnosis.
- ▪
  High protein concentration (>2.0 g/dL), particularly in acute presentation
- ▪
  Serum-ascites albumin gradient is usually >1.1.
- ▪
  White blood cell count is usually <500/mm ³ .
5.
Differential diagnosis includes the following:
- ▪
  Right-sided heart failure
- ▪
  Constrictive pericarditis
- ▪
  Metastatic disease involving the liver
- ▪
  HCC
- ▪
  Alcoholic liver disease
- ▪
  Granulomatous liver disease

Diagnosis

1.
A high index of suspicion is necessary for diagnosis because clinical manifestations and laboratory results are nonspecific.
2.
Imaging techniques for visualizing hepatic veins
- a.
  Ultrasonography
  - ▪
    Color-flow Doppler ultrasonography is better than duplex ultrasonography, which is superior to real-time ultrasonography.
  - ▪
    Provides cost-effective confirmation of low or absent hepatic venous blood flow
  - ▪
    Occasionally can visualize thrombus within hepatic veins
  - ▪
    The sensitivity of color-flow Doppler ultrasonography is 85% to 90%, with similar specificity.
- b.
  MRI with gadolinium contrast and/or pulsed sequencing
  - ▪
    Can visualize thrombus and detect absence of hepatic venous blood flow
  - ▪
    Higher cost than Doppler ultrasonography
  - ▪
    Sensitivity and specificity are approximately 90%.
- c.
  Three-phase CT
  - ▪
    Provides 85% to 90% sensitivity and specificity ( Fig. 21.1 ).
  - ▪
    Can detect multifocal regenerative nodules (some of which are > 2 cm) that develop in some patients
  - ▪
    Perfusion abnormalities may result in a “nutmeg” appearance of the congested liver.
  - ▪
    The caudate lobe is hypertrophied in 75% of patients due to the separate venous drainage of the caudate lobe.
3.
Hepatic venography
- ▪
  Identifies thrombus within hepatic veins
- ▪
  “Spider-web” pattern of collateral vessels in chronic BCS
- ▪
  Inability to cannulate the hepatic vein orifices
- ▪
  Unnecessary if characteristic findings are noted on noninvasive imaging
- ▪
  Usually performed in conjunction with therapeutic intervention such as TIPS
4.
Pathologic findings on liver biopsy specimens
- ▪
  Evidence of high-grade venous congestion
- ▪
  Centrilobular liver cell atrophy
- ▪
  Thrombi within terminal hepatic venules are rarely seen.
- ▪
  Heterogeneous involvement of the liver is occasionally problematic (i.e., sampling error).
5.
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.

Treatment

1.
Medical therapy provides short-term symptomatic benefit and is recommended as a first step.
- ▪
  Diuretics are useful for relieving ascites but do not alter the long-term outcome.
- ▪
  Anticoagulation with heparin followed by warfarin is recommended in all patients. It prevents repeat thromboses in patients with defined thrombotic disorders but may not relieve symptoms in the long term.
- ▪
  Thrombolytic therapy has been used successfully in a few reported cases, although the long-term benefit is unclear.
2.
Minimally invasive approaches
- a.
  Rationale
  - ▪
    Hepatocellular injury may result from microvascular ischemia due to congestion.
  - ▪
    Portosystemic shunting provides a low-pressure path to decompress the congested liver.
- b.
  Angioplasty of short-segment obstructions such as webs or short hepatic vein stenoses; relief of obstruction is temporary, and repeated treatment is required for long-term management.
  - ▪
    Placement of metal stents in the hepatic veins following angioplasty of short-segment stenoses has been used to improve long-term patency.
  - ▪
    Placement of stents in the vena cava provides relief of compression from an enlarged caudate lobe and can be followed by a side-to-side portacaval or mesocaval shunt, if necessary.
- c.
  TIPS can be performed in >90% of patients despite occlusion of hepatic veins.
  - ▪
    The mortality rate is <2%; complication rates are 15% to 20%.
  - ▪
    The liver transplant–free 5-year survival rate is approximately 85%.
  - ▪
    Coated stents have better long-term patency rates.
  - ▪
    Refractory encephalopathy develops in < 10% of patients; it may require LT.
3.
LT
- ▪
  Corrects some underlying clotting disorders and restores hepatocellular function
- ▪
  Actuarial 3-year survival rates are 80%, and 5-year survival rates are approximately 70%; survival rates have improved substantially since 2005.
- ▪
  Recommended in patients with hepatic decompensation who do not respond to minimally invasive procedures
- ▪
  BCS can recur in the posttransplant liver.
4.
Transcardiac membranotomy has been used to relieve membranous obstruction of the IVC and rarely the hepatic veins. Other surgical procedures have been used in small numbers of patients with BCS from other causes. The results have been variable and are subject to the bias of reporting successes more often than failures.
5.
Surgical portosystemic shunting was the mainstay of treatment for BCS before less invasive procedures such as TIPS were used widely; shunts remain an option but are no longer the preferred approach to management due to the high rate of complications.
- a.
  Options include the following:
  - ▪
    Side-to-side portacaval shunt
  - ▪
    Mesocaval shunt
  - ▪
    Mesoatrial shunt
  - ▪
    Side-to-side portacaval with cavoatrial shunt
- b.
  Success of portosystemic shunting depends on the following:
  - ▪
    Experience of the surgeon with a particular shunt
  - ▪
    The underlying disease
  - ▪
    Host factors, including the extent of fibrosis or presence of cirrhosis
  - ▪
    Overall hepatic function at the time of operation
- c.
  Patency rates of 65% to 95% depend on the following:
  - ▪
    Duration of disease: The longer the duration, the lower the patency
  - ▪
    Presence of fibrosis or cirrhosis: Lower patency rates
  - ▪
    The type of shunt: Rates for mesoatrial shunts are slightly lower than those for mesocaval shunts.
  - ▪
    Continued thrombotic diathesis from the underlying disease
- d.
  Survival rates of 38% to 87% at 5 years depend on the following:
  - ▪
    Continued patency of the graft
  - ▪
    Degree of fibrosis
  - ▪
    Type of shunt

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here