European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol. 2016 Jan;64(1):179-202. doi: 10.1016/j.jhep.2015.07.040. Epub 2015 Oct 26. PubMed PMID: 26516032.
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 oral contraceptives and inflammatory bowel disease.
Clinical Features and Natural HistoryTop
The presentation of BCS 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.
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) is used for diagnosing intrahepatic causes of BCS (eg, tumors or abscesses adjacent to the hepatic veins). CT can visualize abnormalities of hepatic parenchymal perfusion, which may be so severe that they resemble a tumor.
3. Phlebography and magnetic resonance angiography (MRA)—in particular traditional phlebography (cavography)—can accurately identify the location and extent of thrombosis or other causes of venous flow obstruction. Phlebography should be considered when noninvasive tests are inconclusive and there is still a strong clinical suspicion for BCS.
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 transplantation. Heart failure and pericardial disease should also be excluded.
The rates of 3-year survival without treatment are ~10%. The 5-year survival rate with treatment is ~75%.
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) followed by a vitamin K antagonist (VKA). There is less data and experience with direct oral anticoagulants (DOACs), but they may be a reasonable second option.
3. Treatment of complications (ascites, esophageal varices).
1. All patients who present with acute liver failure should be referred for a liver transplantation 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 transplantation referral.
Treat complications of portal hypertension. Consider referral for liver transplantation, especially in the setting of cirrhosis and hepatocellular carcinoma.