Budd Chiari Syndrome

Budd-Chiari syndrome (BCS) refers to the noncardiogenic obstruction of hepatic venous flow at any level above the venule. Budd-Chiari syndrome should be considered separate from veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, which is characterized by toxin-induced nonthrombotic obstruction of prehepatic veins.

Occlusion of a single hepatic vein is usually silent. Overt Budd-Chiari syndrome generally requires the occlusion of at least 2 hepatic veins. Venous congestion of the liver causes hepatomegaly, which can stretch the liver capsule and be very painful. Enlargement of the caudate lobe is common because blood is shunted through it directly into the inferior vena cava (IVC).

Hepatic function can be affected to a degree, depending on the amount of stasis and resultant hypoxia. Increased sinusoidal pressure can itself cause hepatocellular necrosis. Up-regulation of specific genes in chronic Budd-Chiari syndrome contributes to liver destruction through the stimulation of extracellular matrix proliferation, which contributes to liver fibrosis. Most common, matrix metalloproteinase 7 and superior cervical ganglion 10 (SCG10), which are increased in expression, and thrombospondin-1, which is decreased.

Budd-Chiari syndrome is extremely rare, and the incidence is not well reported in the literature; however, membranous (or congenital) forms of Budd-Chiari syndrome are the most common cause of Budd-Chiari syndrome worldwide, particularly in Asia.The mortality rate can be high in patients who develop fulminant hepatic failure. Morbidity and mortality are generally related to complications of liver failure andascites. The type of concomitant underlying disease, if any, can also impact morbidity and mortality. Long-term observation in adults has demonstrated 10-year survival rates as high as 55%.

Patients with acute onset of obstruction typically present with acute right upper quadrant pain. Abdominal distention can also be a significant symptom because ascites develop. Jaundice is rarely observed.Various symptoms that are potentially related to underlying and predisposing conditions can accompany the onset of Budd-Chiari syndrome (BCS). If the liver has had time to develop collaterals and decompress, patients can be asymptomatic or present with few symptoms. Progression of Budd-Chiari syndrome can lead to liver failure and portal hypertension with corresponding symptoms (eg, encephalopathy, hematemesis).

Physical

Tender hepatomegaly with ascites and splenomegaly are common findings. Engorgement of the vessels of the chest and abdominal wall can also be observed. Bilirubin and transaminases are often mildly elevated. Prolongation of the prothrombin time (PT) is common and can be confusing in the setting of a hypercoagulable state.

Causes

Budd-Chiari syndrome can frequently be idiopathic; however, several main causes of this disorder are noted.

• Mechanical causes
  

  • Congenital membranous obstruction
    • Type I: Thin membrane is present at the vena cava or atrium.
    • Type II: A segment of the vena cava is absent.
    • Type III: The inferior vena cava (IVC) cannot be filled, and collaterals have developed.
  • Hepatic venous stenosis
  • Hypoplasia of the suprahepatic veins
  • Postsurgical obstruction
  • Posttraumatic obstruction
  • Tumor invasion
  • Total parenteral nutrition (TPN): BCS has been reported as a complication of TPN via an IVC catheter in a neonate.
• Causes related to hypercoagulable states
  

  • Hematologic disorders
    • Polycythemia vera
    • Essential thrombocytosis
    • Paroxysmal nocturnal hemoglobinuria
    • Myeloproliferative disorders, which may account for almost half of cases
  • Coagulopathies
    • Factor V Leiden mutation
    • Protein C deficiency
    • Protein S deficiency
    • Antithrombin II deficiency
  • Antiphospholipid antibody syndrome
  • Other causes of hypercoagulability
    • Collagen vascular diseases
    • Sickle cell disease
    • Inflammatory bowel disease
    • Oral contraceptives
    • Postpartum malignancy
• Causes related to infection
  

  • Tuberculosis
  • Aspergillosis
  • Filariasis
  • Echinococcus

  
  

  Differentials

  • Appendicitis
  • Biliary Atresia
  • Chronic Granulomatous Disease
  • Congenital Hepatic Fibrosis
  • Cystic Fibrosis
  • Cytomegalovirus Infection
  • Intestinal Malrotation
  • Intussusception
  • Multicystic Renal Dysplasia
  • Nephrotic Syndrome
  • Pancreatitis and Pancreatic Pseudocyst
  • Pericarditis, Constrictive
  • Syphilis
  • Toxoplasmosis

  Imaging Studies

  • Budd-Chiari syndrome is usually diagnosed initially using Doppler ultrasonography, which has a sensitivity and specificity of 85% or higher.
  • Detailed imaging studies are required to determine precisely the level and degree of obstruction. CT scanning can rarely provide such detail, unless a mechanical obstruction, such as a locally invading tumor, is suspected.
  • MRI, which has a sensitivity and specificity of 90% or higher, is becoming increasingly useful in providing less-invasive venography, angiography, and cholangiography. MRI may assist in differentiating acute from chronic Budd-Chiari syndrome because it is able to provide a larger image of the vasculature, as well as determine if edema of the parenchyma is present (acute form).
    
    

    Procedures

    • Interventional radiology: Catheterization and venography can clearly delineate the nature and severity of the obstruction. Occasionally, therapeutic interventions can be undertaken at the same time, and they can include balloon angioplasty, placement of a stent, localized thrombolysis, or transjugular intrahepatic portacaval shunt (TIPS).
    • Paracentesis: The benefits of therapeutic paracentesis must be carefully weighed against the significant risks that can be associated with this procedure.
    • Percutaneous liver biopsy: Liver biopsy can be of prognostic assistance, particularly if liver transplantation is being considered, to establish the degree of hepatocellular damage and the presence and degree of fibrosis.

    Histologic Findings

    • Histologic findings can range from nearly normal to severe chronic congestion with fibrosis, reversed lobulation, and dilated lymphatic channels.
    • The most severe end of this spectrum can include fulminant hepatic failure with massive centrilobular necrosis.
    • Adult studies have shown that early pathology related to Budd-Chiari syndrome did not have a significant impact on survival.
      
      

      Medical Care

      In patients with Budd-Chiari syndrome (BCS), aggressively seek specific therapy aimed at correcting or alleviating the obstruction. Also treat underlying conditions aggressively. Symptomatic treatment for Budd-Chiari syndrome includes diuretics and therapeutic paracentesis, when necessary (can be associated with catastrophic complications, bacterial peritonitis).

      
      
      
      

      • Patients with liver failure and ascites have total body sodium overload, despite typically low serum sodium concentrations. Inducing negative sodium balance can reduce the amount of ascites. Take special care when using diuretics to avoid inducing hepatorenal syndrome or creating electrolyte and fluid disturbances through overly aggressive diuresis. Secondaryhyperaldosteronism is a part of this clinical picture, making spironolactone typically the first-line diuretic. Chlorothiazide or furosemide is often added, which can provide synergy and avoid hyperkalemia.
      • The benefits of therapeutic paracentesis must be carefully weighed against the significant risks that can be associated with this procedure.
      • Anticoagulation is frequently used in hypercoagulable states.
        
        

        Surgical Care

        • Mesocaval shunt
        • Mesoatrial shunt
        • Portacaval shunt
        • Liver transplantation: One study reported that, out of almost 79,000 liver transplantations in the United States from 1987-2006, 510 were for Budd-Chiari syndrome. Graft survival was as high as 85%.

        Consultations

        • Consultants should be selected based on the individual clinical situation.
        • Early involvement of a hepatologist can help to establish the direction of workup and therapy.
        • Consultation with interventional radiologists, hematologists, oncologists, and general surgeons may be required, depending on the situation.

        Diet

        • Sodium restriction can be an important part of maintaining a negative sodium balance.
      • Systemic thrombolysis can be a high-risk endeavor, and local thrombolysis performed by an interventional radiologist is preferable.
      • Other radiologic interventions available include balloon angioplasty, placement of stents, and transjugular intrahepatic portacaval shunt (TIPS). Adult studies suggest that the use of TIPS is safe and increases survival in patients with progressive liver disease and profound involvement of the hepatic vasculature due to Budd-Chiari syndrome who have failed medical therapy.
      • A stepwise approach of anticoagulation, vascular intervention, TIPS and transplant can increase survival among patients.
        
        

        Medication Summary

        Medications commonly used in patients with Budd-Chiari syndrome (BCS) include diuretics, anticoagulants, and thrombolytics. The therapeutic interventions used (medical or otherwise) must be tailored to each patient's condition. The use of thrombolytics should be reserved for experts familiar with the special circumstances in which they may be appropriate. Use of anticoagulants should be directed towards therapy of an underlying coagulopathy. Typically, the decision to use anticoagulants is made with the assistance and guidance of a pediatric hematologist.

        Diuretic agents

        Class Summary

        Diuretics can be useful to reduce the amount of ascites, providing symptomatic relief and reducing the need for paracentesis.

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        Spironolactone (Aldactone)

        Potassium-sparing diuretic. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

        Spironolactone is often preferred because of its potassium-sparing effects, particularly in a clinical setting that includes secondary hyperaldosteronism.

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        Furosemide (Lasix)

        Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, results inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.

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        Chlorothiazide (Diuril, Diurigen)

        Thiazide diuretic. Inhibits sodium-chloride symport, blocking sodium reabsorption in the distal convoluted tubule.

        
        

        Further Inpatient Care

        • For patients with Budd-Chiari syndrome (BCS), hospitalization is generally required for diagnostic evaluation and interventions.
        • Patients with lesions that are amenable to balloon dilatation or stents require follow-up catheterizations and frequently repeat dilatations or replacement of stents.

        Complications

        • Complications are generally related to associated liver failure.
        • Bacterial peritonitis is always of concern in the patient with ascites, especially if paracentesis is undertaken.
        • Complications must also be considered in relation to therapies used (eg, thrombolytics).

        Prognosis

        • Long-term follow-up in adults has demonstrated 10-year survival rate as high as 55%.
        • A few adult studies have identified factors that predicted worse overall survival of patients with Budd-Chiari syndrome. These include older age, male gender, presentation with significant disease, no treatment with transjugular intrahepatic portacaval shunt (TIPS), and an increasing Child–Pugh–Turcotte score.