Budd-Chiari Syndrome (Including Hepatic Vein Thrombosis)

Definition, Etiology, PathogenesisTop

Budd-Chiari syndrome (BCS) refers to a partial or complete obstruction of the hepatic venous outflow tract that is not due to heart failure, pericardial disease, or sinusoidal obstruction syndrome.

Based on etiology, BCS is classified into primary or secondary. Hepatic vein thrombosis and inferior vena cava thrombosis refer to primary BCS. Secondary BCS occurs in the setting of either external compression or infiltration of the hepatic vein or inferior vena cava (or both) by a lesion other than thrombosis or phlebitis (eg, malignancy).

Causes: The underlying etiology can be established in 80% of patients. The most frequent causes of BCS include myeloproliferative neoplasms, neoplastic and nonneoplastic lesions of the liver (hepatocellular carcinoma being the most common neoplastic lesion), and hypercoagulable states including hereditary thrombophilias, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, oral contraceptives, and inflammatory bowel disease.

Clinical Features and Natural HistoryTop

The presentation of BCS (but not the extent of clot/disease burden) is highly variable. Patients may be initially asymptomatic (15%-20%) for an extended period of time when the disease is limited to one hepatic vein and collateral circulation is well developed. Acute thrombosis of 3 hepatic veins leads to acute liver failure with rapidly developing ascites. However, the course of the disease is often subacute (as collateral hepatic veins develop) or chronic (this may progress to cirrhosis) and includes hepatomegaly, slowly developing ascites, jaundice, features of liver failure, and edema of the lower extremities. Accordingly, clinicians should consider this diagnosis in patients presenting with a clinical picture of acute liver failure, acute hepatitis, or chronic liver disease.

DiagnosisTop

Diagnostic Tests

1. Doppler ultrasonography can often establish the diagnosis of BCS by revealing an abnormal flow pattern and occlusion of hepatic veins. It can also be used to evaluate for chronic BCS by identifying the presence of venous collaterals. Caudate lobe hypertrophy, another sign of chronic BCS identified on ultrasonography, can exacerbate the outflow obstruction through external compression of the intrahepatic component of the inferior vena cava.

2. Computed tomography (CT) and magnetic resonance venography (MRV) can accurately identify the location and extent of thrombosis and assess for potential causes of venous flow obstruction (eg, tumor).

Differential Diagnosis

Hepatic veno-occlusive disease, a disease of small intrahepatic veins, has clinical features that closely resemble BCS. It is often observed within 100 days of anticancer chemotherapy or bone marrow transplant. Heart failure and pericardial disease should also be excluded.

TreatmentTop

The rates of 3-year survival without treatment are ~10%. The 5-year survival rate with treatment is ~75%.

Key Principles

1. Treatment of the predisposing condition when possible.

2. Initiate anticoagulation in all patients who present with BCS, unless there are contraindications. Typically use 5 to 7 days of low-molecular-weight heparin (LMWH) overlapped with initiation of vitamin K antagonist (warfarin). There is less data and experience with direct oral anticoagulants (DOACs), but they may be a reasonable alternative.

3. Treatment of complications (ascites, esophageal varices).

Acute Symptomatic Budd-Chiari Syndrome

1. All patients who present with acute liver failure should be referred for a liver transplant assessment.

2. Thrombolysis may be attempted in the first 2 or 3 weeks of the disease if a well-defined clot is present. If there are contraindications to thrombolytics and the patient is symptomatic from the obstruction, angioplasty and stenting may be considered. Other options include transjugular intrahepatic portosystemic shunt (TIPS) and surgical shunts. Failure to improve with the above managements is also an indication for a liver transplant referral. In general, early collaboration with a local liver transplant center is encouraged to assist in guiding management.

Subacute and Chronic Budd-Chiari Syndrome

Treat complications of portal hypertension. Consider referral for liver transplant, especially in the setting of cirrhosis and hepatocellular carcinoma.

Special ConsiderationsTop

Pregnancy

In pregnant women, Doppler ultrasound is the examination of choice in the diagnosis of Budd-Chiari syndrome. LMWH is used in the treatment (vitamin K antagonists [VKAs] are contraindicated in pregnancy but can be used during breastfeeding). Specialist multidisciplinary input is essential.