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Pediatrics: General Medicine > Gastroenterology
Budd-Chiari Syndrome
Article Last Updated: Jul 25, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Cass Smith, MD, Fellow, Pediatric Gastroenterology, Children's Hospital of Wisconsin
Coauthor(s):
Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Associate Professor, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania;
Michael Stephens, MD, Assistant Professor, Department of Pediatrics, Section of Gastroenterology and Nutrition, Children's Hospital of Wisconsin
Editors: Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Associate Professor, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health; Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
Budd-Chiari syndrome, BCS, membranous Budd-Chiari syndrome, membranous BCS, hepatic vein thrombosis, congenital Budd-Chiari syndrome, congenital BCS
Background
Budd-Chiari syndrome (BCS) refers to the noncardiogenic obstruction of hepatic venous flow at any level above the venule. Obstruction can result from a variety of conditions, particularly prothrombotic states. BCS 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.
Pathophysiology
Occlusion of a single hepatic vein is usually silent. Overt BCS generally requires the occlusion of at least two 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 dependent on the amount of stasis and resultant hypoxia. Increased sinusoidal pressure can itself cause hepatocellular necrosis. Recent literature also suggests that upregulation of specific genes in chronic BCS contributes to liver destruction through the stimulation of extracellular matrix proliferation, which contributes to liver fibrosis. The most prominent genes involved include matrix metalloproteinase 7 and superior cervical ganglion 10 (SCG10), which are increased in expression, and thrombospondin-1, which is decreased (Paradis, 2005).
Frequency
International
BCS is extremely rare, and the incidence is not well reported in the literature; however, membranous (or congenital) forms of BCS are the most common cause of BCS worldwide, particularly in Asia.
Mortality/Morbidity
The mortality rate can be high in patients who develop fulminant hepatic failure. Morbidity and mortality are generally related to complications of liver failure and ascites. 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%.
Sex
No data exist to suggest that sex affects predisposition. However, in the United States, BCS is predominantly seen in women and is associated with hematologic disorders.
Age
BCS is rare in the general population and even more so in children. Peak incidence seems to be in persons aged 40-50.
History
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. A variety of other symptoms, which could be related to underlying and predisposing conditions, can accompany the onset of BCS. If the liver has had time to develop collaterals and decompress, patients can be asymptomatic or present with few symptoms. Progression of BCS 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 often are mildly elevated. Prolongation of the prothrombin time (PT) is common and can be confusing in the setting of a hypercoagulable state.
Causes
BCS can frequently be idiopathic; however, several main causes of this disorder exist.
- 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 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
- 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
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
Other Problems to be Considered
Cirrhosis
Neonatal hemochromatosis
Alpha1-antitrypsin deficiency
Infectious hepatitis
Niemann-Pick disease type C
Perforated common bile duct
Meconium peritonitis
Jejunal atresia
Intestinal perforation
Serositis
Eosinophilic enteritis
Henoch-Schönlein purpura
Parvovirus
Central venous hyperalimentation
Obstructive uropathy
Congestive heart failure
Dysrhythmia
Chylous ascites
Neoplasm
Inborn error of metabolism
Pseudoascites - Small intestinal duplication
Celiac disease
Fitz-Hugh Curtis syndrome
Lab Studies
- Evaluate for underlying predisposing conditions, such as malignancy or especially hypercoagulable states, and institute appropriate therapy.
Imaging Studies
- BCS 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.
- Magnetic resonance imaging (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 BCS, as 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 BCS did not have a significant impact on survival (Tang, 2001).
Medical Care
Aggressively seek specific therapy aimed at correcting or alleviating the obstruction. Also treat underlying conditions aggressively. Symptomatic treatment for BCS includes diuretics and therapeutic paracentesis, when necessary (can be associated with catastrophic complications, such as 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. Secondary hyperaldosteronism 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.
- 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 TIPS. Recent 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 BCS who have failed medical therapy (Khuroo, 2005).
Surgical Care
- Mesocaval shunt
- Mesoatrial shunt
- Portacaval shunt
- Liver transplantation
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. Help is often requested of interventional radiologists, hematologists, oncologists, and general surgeons, depending on the situation.
Diet
Sodium restriction can be an important part of maintaining a negative sodium balance.
Medications commonly employed in patients with 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.
Drug Category: Diuretic agents
Diuretics can be useful to reduce the amount of ascites, providing symptomatic relief and reducing the need for paracentesis.
| Drug Name | Spironolactone (Aldactone) |
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| Description | 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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| Adult Dose | 25-200 mg/d PO divided bid/qid; not to exceed 200 mg/d |
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| Pediatric Dose | 1-3.3 mg/kg/d PO divided bid/qid |
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| Contraindications | Documented hypersensitivity; anuria; renal failure; hyperkalemia |
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| Interactions | May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone |
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| Pregnancy | D - Unsafe in pregnancy
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| Precautions | Caution in renal and hepatic impairment; gynecomastia, impotence, decreased libido, hirsutism, deepening of the voice, menstrual irregularities, diarrhea, gastritis, gastric bleeding, drowsiness, ataxia, confusion, and headache; possible rash and blood dyscrasias |
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| Drug Name | Furosemide (Lasix, Furomide) |
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| Description | 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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| Adult Dose | 20-80 mg/d PO divided q6-12h; not to exceed 600 mg/d |
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| Pediatric Dose | Neonates:
0.5-1 mg/kg/dose PO q8-24h; not to exceed 6 mg/kg/dose
2 mg/kg/dose IV qd/bid
Infants and children: 0.5-2 mg/kg/dose PO/IV q6-12h; not to exceed 6 mg/kg/dose |
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| Contraindications | Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion |
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| Interactions | Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | Possible ototoxicity, most frequently with rapid IV infusion; possible disturbances in fluid and electrolyte balance |
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| Drug Name | Chlorothiazide (Diuril, Diurigen) |
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| Description | Thiazide diuretic. Inhibits sodium-chloride symport, blocking sodium reabsorption in the distal convoluted tubule. |
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| Adult Dose | 250-1000 mg/dose PO qd/qid; not to exceed 2 g/d |
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| Pediatric Dose | <6 months: 20-40 mg/kg/d PO divided q12h; not to exceed 375 mg/d
>6 months: 20 mg/kg/d PO divided q12h; not to exceed 1 g/d |
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| Contraindications | Documented hypersensitivity; anuria |
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| Interactions | Quinidine (torsades de pointes); possible decreased effects of anticoagulants, uricosuric agents, sulfonylureas, and insulin; possible increased effects of anesthetics, diazoxide, digitalis glycosides, lithium, loop diuretics, and vitamin D; possible reduced thiazide diuretics effectiveness when used with NSAIDs, bile acid sequestrants, and methenamines; increased risk of hypokalemia with coadministration of amphotericin B and corticosteroids |
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| Pregnancy | D - Unsafe in pregnancy
|
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| Precautions | Fluid and electrolyte disturbances; extracellular volume depletion, hypotension, hypokalemia, hyponatremia, hypochloremia, metabolic acidosis, hypomagnesemia, hyperkalemia, hyperuricemia, and hyperbilirubinemia; possible decreased glucose tolerance |
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Further Inpatient Care
- For patients with 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 BCS. These include older age, male gender, presentation with significant disease, no treatment with TIPS, and an increasing Child–Pugh–Turcotte score (Khuroo, 2005).
Medical/Legal Pitfalls
- BCS is a rare and serious disorder in children. Many of the therapeutic interventions available are invasive and require highly specialized expertise. Early referral to an appropriate tertiary care center should be considered.
| Media file 1:
Ultrasound showing hepatic vein thrombus with vessels forming arrow pointing to the thrombus. |
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Media type: Image
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| Media file 3:
Calcified thrombus in the IVC of a neonate secondary to UVC. |
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Media type: X-RAY
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Budd-Chiari Syndrome excerpt Article Last Updated: Jul 25, 2006
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