Hepatic Vein Thrombosis (Budd-Chiari Syndrome)

Epidemiology

Age
- Usually Presents in 20’s-30’s: although it may occur in children or older adults
- In Asian Countries, Median Age of Presentation is 45 y/o
Sex
- In Non-Asian Countries, Hepatic Vein Thrombosis is More Common in Females
- In Asian Countries, Occurs More Commonly in Males

Etiology

General Comments
- 80% of Hepatic Vein Thrombosis Cases Have an Underlying Disorder
Malignancy
- Epidemiology: malignancy accounts for 10% of hepatic vein thrombosis cases
- Mechanisms
  - Direct Compression of Hepatic Vascular Structures
  - Invasion of Vascular Structures
- Hepatocellular Carcinoma (see Hepatocellular Carcinoma)
  - Associated with Membranous Obstruction of Inferior Vena Cava
- Adrenocortical Carcinoma (see Adrenocortical Carcinoma)
- Renal Carcinoma (see Renal Cancer)
- Right Atrial/Inferior Vena Cava/Hepatic Vein Sarcoma
- Lung Cancer (see Lung Cancer)
- Pancreatic Cancer (see Pancreatic Cancer)
- Gastric Cancer (she Gastric Cancer)
Hypercoagulable State (see Hypercoagulable States)
- Hormonal
  - Oral Contraceptives (OCP) (see Oral Contraceptives)
  - Pregnancy (see Pregnancy)
- Myeloproliferative Disease: accounts for up to 50% of hepatic vein thrombosis cases
  - General Comments: the JAK2 (V617F) mutation is present in 26-59% of hepatic vein thrombosis cases (JAK/STAT pathway plays a critical role in cellular proliferation and cell survival)
  - Primary Myelofibrosis (see Primary Myelofibrosis)
    - JAK2 (V617F) Mutation is Present in Approximately 60% of Primary Myelofibrosis Cases
  - Essential Thrombocytosis (see Essential Thrombocythemia)
    - JAK2 (V617F) Mutation is Present in Approximately 50% of Essential Thrombocythemia Cases
  - Polycythemia Vera (see Polycythemia Vera)
    - JAK2 (V617F) Mutation is Present in Almost All Cases of Polycythemia Vera
- Other Hypercoagulable States
  - Prothrombin G20210A Gene Mutation (see Prothrombin G20210A Gene Mutation)
  - Antiphospholipid Antibody Syndrome (see Antiphospholipid Antibody Syndrome)
  - Antithrombin Deficiency (see Antithrombin Deficiency)
  - Factor V Leiden Gene Mutation (G1691A) (see Factor V Leiden): which produces activated protein C resistance
  - Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria)
  - Protein C Deficiency (see Protein C Deficiency)
  - Protein S Deficiency (see Protein S Deficiency)
Infection/Space-Occupying Liver Lesions: account for 10% of hepatic vein thrombosis cases
- Abdominal Aortic Aneurysm (AAA) (see Abdominal Aortic Aneurysm)
- Invasive Aspergillosis (see Invasive Aspergillosis)
- Hepatic Adenoma
- Hepatic Cyst
- Hepatic Mucinous Cystic Neoplasm (Cystadenoma)
- Hepatic Tumor
- Mucormycosis (see Mucormycosis)
- Pyogenic Liver Abscess (see Pyogenic Liver Abscess)
- Syphilitic Gumma (see Syphilis)
Rheumatologic
- Behcet’s Syndrome (see Behcets Disease)
- Mixed Connective Tissue Disease (MCTD) (see Mixed Connective Tissue Disease)
- Sjogren’s Syndrome (see Sjogren’s Syndrome)
- Systemic Lupus Erythematosis (SLE) (see Systemic Lupus Erythematosus)
Other
- Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency)
- Familial Hepatic Vein Thrombosis
  - Epidemiology: rare
- Hypereosinophilic Syndrome (see Hypereosinophilic Syndrome)
- Idiopathic Granulomatous Venulitis
- Idiopathic Hepatic Vein Thrombosis: accounts for 20% of hepatic vein thrombosis cases
- Inflammatory Bowel Disease (IBD) (see Inflammatory Bowel Disease)
- Laparoscopic Cholecystectomy (see Cholecystectomy)
- Membranous Webs (Partial or Complete) of the Inferior Vena Cava and/or Hepatic Veins
  - Membranous Webs May Be Congenital or Due to Myeloproliferative Disease
  - Membranous Webs are Associated with the Subsequent Development of Hepatocellular Carcinoma
- Minimal Change Nephrotic Syndrome (see Nephrotic Syndrome)
- Neurofibromatosis (see Neurofibromatosis)
- Protein Losing Gastroenteropathy (see Protein Losing Gastroenteropathy)
- Sarcoidosis (see Sarcoidosis)
- Torsion of the Liver
- Trauma

Physiology

Background

Liver has Complex Vascular Supply and High Metabolic Rate: makes it vulnerable to circulatory dysfunction from a variety of etiologies
- Congestive Hepatopathy (see Congestive Hepatopathy): passive hepatic congestion, usually attributable to right-sided congestive heart failure (with or without decreased cardiac output
- Hepatic Infarction (see Hepatic Infarction)
- Hepatic Sinusoidal Obstruction Syndrome
- Hepatic Vein Thrombosis (Budd-Chiari Syndrome)
- Ischemic Hepatitis (Hypoxic Hepatitis) (see Ischemic Hepatitis)

Budd-Chiari Syndrome is Due to Hepatic Vein Obstruction

Obstruction Must Be Due to Predominantly Venous Process (Venous Thrombosis or Phlebitis) and Cannot Be Due to Cardiac Disease, Pericardial Disease, Sinusoidal Obstruction (Hepatic Veno-Occlusive Disease)
- Primary Budd-Chiari Syndrome
  - Obstruction Must Be Due to Predominantly Venous Process (Venous Thrombosis or Phlebitis) and

Diagnosis

Right Upper Quadrant Ultrasound (see Abdominal-Pelvic Ultrasound)

Rationale
- Doppler Ultrasound is Useful to Exclude the Diagnosis of Portal Vein Thrombosis, Hepatic Artery Thrombosis, and/or Hepatic Vein Thrombosis

Abdominal/Pelvic CT (see Abdominal-Pelvic Computed Tomography)

Findings
- Ascites
- Delayed or Absent Hepatic Vein Filling
- Mottled Appearance of Liver

Abdominal/Pelvic MRI (see Abdominal/Pelvic Magnetic Resonance Imaging)

Diagnostic

Inferior Vena Cava Venogram (see Inferior Vena Cava Venogram)

Diagnostic Gold Standard
- However, it is Rarely Required for Diagnosis

Paracentesis (see Paracentesis)

Findings
- Consistent with Portal Hypertension: usually not specifically helpful in making the diagnosis

Liver Biopsy (Liver Biopsy)

Liver Biopsy is Rarely Required to Diagnose Budd-Chiari Syndrome
Findings
- Areas of Hepatic Necrosis
- Hepatic Congestion
- Hepatic Fibrosis/Cirrhosis: seen only late in the course

Clinical Manifestations

Acute Hepatic Failure (see Acute Hepatic Failure)

Abdominal Pain (see Abdominal Pain)
- Clinical
  - RUQ Abdominal Pain
Acute Liver Injury with Transaminitis/Hyperbilirubinemia (Jaundice) (see Hyperbilirubinemia)
Coagulopathy with Elevated INR (see Coagulopathy)
Hepatic Encephalopathy (see Hepatic Encephalopathy)
- Epidemiology
  - Develops within 8 wks after the development of Jaundice
Hepatomegaly (see Hepatomegaly)

Acute Hepatic Vein Thrombosis

Onset
- Development of Clinical Manifestations Over the Course of Weeks
Ascites (see Ascites)
- Epidemiology
  - XXXX
- Clinical
  - Typically Intractable
Hepatic Necrosis

Subacute Hepatic Vein Thrombosis

Onset
- Insidious with Development of Symptoms Over Up to 3 mo
Ascites (see Ascites)
- Epidemiology: xxx
- Clinical: may be minimal (due to decompression of hepatic sinusoids by portal and hepatic venous collaterals)

Chronic Hepatic Vein Thrombosis

Onset
- Presentation with Complications of Cirrhosis
xxxx

Treatment

Anticoagulation

Agents
- Unfractionated Heparin Drip (see Heparin)
- xxxx

Thrombolysis

xxx

Angioplasty

xxxx

Liver Transplant (see Liver Transplant)

For Cases with Cirrhosis/End-Stage Liver Disease

Prognosis

Mortality Rate
- Untreated: high mortality rate with 90% of patients dying with 3 yrs (Gastroenterology, 1975) [MEDLINE]
- Treated (Ann Intern Med, 2009) [MEDLINE]
  - 1-Year Survival: 87%
  - 2-Year Survival: 82%
  - 5-Year Survival: 74%
Factors Associated with Poor Prognosis
- Chronic Disease at Presentation
- More Severe Liver Failure
- Occlusion of Portal Vein
- Older Age at Time of Diagnosis
- Refractory Ascites

References

The Budd-Chiari syndrome: correlation between hepatic scintigraphy and the clinical, radiological, and pathological findings in nineteen cases of hepatic venous outflow obstruction. Gastroenterology. 1975;68(3):509 [MEDLINE]
Vascular disorders of the liver. Hepatology. 2009 May;49(5):1729-64. doi: 10.1002/hep.22772 [MEDLINE]
Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med. 2009 Aug 4;151(3):167-75 [MEDLINE]
Budd-Chiari syndrome. AJR Am J Roentgenol. 2012 Oct;199(4):737-45 [MEDLINE]
Management of hepatic vascular diseases. J Hepatol. 2012;56 Suppl 1:S25-38. doi: 10.1016/S0168-8278(12)60004-X [MEDLINE]
Budd-Chiari syndrome. United European Gastroenterol J. 2015;3(6):489-500 [MEDLINE]