Obstruction of hepatic venous outflow can occur in extrahepatic vessels (Budd-Chiari syndrome) or intrahepatic vessels (veno-occlusive disease) but often occurs in both. Obstruction results in congestion of the sinusoids, hepatomegaly, portal hypertension, reduced portal blood flow, ascites, and splenomegaly.
Budd-Chiari syndrome is obstruction of hepatic venous outflow that originates anywhere from the small hepatic veins inside the liver to the inferior vena cava and right atrium. Manifestations range from no symptoms to fulminant liver failure. Diagnosis is based on ultrasonography. Treatment includes supportive medical therapy and measures to establish and maintain venous patency, such as thrombolysis, decompression with shunts, and long-term anticoagulation.
In the Western world, the most common cause is a clot obstructing the hepatic veins and the adjacent inferior vena cava. Clots commonly result from the following:
Sometimes Budd-Chiari syndrome begins during pregnancy and unmasks a previously asymptomatic hypercoagulability disorder.
The cause of obstruction is often unknown. In Asia and South Africa, the basic defect is often a membranous obstruction (webs) of the inferior vena cava above the liver, likely representing recanalization of a prior thrombus in adults or a developmental flaw (eg, venous stenosis) in children. This type of obstruction is called obliterative hepatocavopathy.
Budd-Chiari syndrome usually develops over weeks or months. When it does, cirrhosis and portal hypertension tend to develop.
Symptoms and Signs
Manifestations range from none (asymptomatic) to fulminant liver failure or cirrhosis. Symptoms vary depending on whether the obstruction occurs acutely or over time.
Acute obstruction (in about 20%) causes fatigue, right upper quadrant pain, nausea, vomiting, mild jaundice, tender hepatomegaly, and ascites. It typically occurs during pregnancy. Fulminant liver failure with encephalopathy is rare. Aminotransferase levels are quite high
Chronic outflow obstruction (developing over weeks to months) may be rather asymptomatic in some until it progresses or may cause fatigue, abdominal pain, and hepatomegaly. Lower-extremity edema and ascites may result from venous obstruction, even in the absence of cirrhosis. Cirrhosis may develop, leading to variceal bleeding, massive ascites, splenomegaly, hepatopulmonary syndrome (see Pulmonary Hypertension: Hepatopulmonary Syndrome), or a combination. Complete obstruction of the inferior vena cava causes edema of the abdominal wall and legs plus visibly tortuous superficial abdominal veins from the pelvis to the costal margin.
Budd-Chiari syndrome is suspected in patients with
Liver function tests are usually abnormal; the pattern is variable and nonspecific. Imaging usually begins with abdominal Doppler ultrasonography, which can show the direction of blood flow and the site of obstruction. Magnetic resonance angiography and CT are useful if ultrasonography is not diagnostic. Conventional angiography (venography with pressure measurements and arteriography) is necessary if therapeutic or surgical intervention is planned. Liver biopsy is done occasionally to diagnose the acute stages and determine whether cirrhosis has developed.
Without treatment, most patients with complete venous obstruction die of liver failure within 3 yr. For patients with incomplete obstruction, the course varies.
Treatment varies according to its onset (acute vs chronic) and severity (fulminant liver failure vs decompensated cirrhosis or stable/asymptomatic). The cornerstones of management are
Aggressive interventions (eg, thrombolysis, stents) are used when the disease is acute (eg, within 4 wk and in the absence of cirrhosis). Thrombolysis can dissolve acute clots, allowing recanalization and so relieving hepatic congestion. Radiologic procedures have a major role using angioplasty, stenting, and portosytemic shunts. For caval webs or hepatic venous stenosis, decompression via percutaneous transluminal balloon angioplasty with intraluminal stents can maintain hepatic outflow. When dilation of a hepatic outflow narrowing is not technically feasible, transjugular intrahepatic portosystemic shunting (TIPS) and various surgical shunts can provide decompression by diversion into the systemic circulation. Portosystemic shunts are generally not used if hepatic encephalopathy is present; such shunts worsen liver function. Further, shunts tend to thrombose, especially when associated with hematologic disorders.
Long-term anticoagulation is often necessary to prevent recurrence. Liver transplantation may be lifesaving in patients with fulminant disease or decompensated cirrhosis.
(Sinusoidal Obstruction Syndrome)
Hepatic veno-occlusive disease is caused by endothelial injury, leading to nonthrombotic occlusion of the terminal hepatic venules and hepatic sinusoids, rather than of the hepatic veins or inferior vena cava (as in Budd-Chiari syndrome).
Venous congestion causes portal hypertension and ischemic necrosis (which leads to cirrhosis).
Common causes include
Initial manifestations include sudden jaundice, ascites, and tender, smooth hepatomegaly. Onset is within the first 3 wk of transplantation in bone marrow or hematopoietic cell recipients, who either recover spontaneously within a few weeks (or sometimes, with mild cases, after an increase in immunosuppressant therapy) or die of fulminant liver failure. Other patients have recurrent ascites, portal hypertension, splenomegaly, and, eventually, cirrhosis.
The diagnosis is suspected in patients with unexplained clinical or laboratory evidence of liver disease, particularly in those with known risk factors, such as bone marrow or hematopoietic cell transplantation. Laboratory results are nonspecific: elevated aminotransferase and conjugated bilirubin levels. PT/INR becomes abnormal when disease is severe. Ultrasonography shows retrograde flow in the portal vein. If the diagnosis is unclear, invasive tests become necessary—eg, liver biopsy or measurement of the portal-hepatic venous pressure gradient (a pressure gradient > 10 mm Hg suggests veno-occlusive disease). Measuring the pressure across the liver entails inserting a catheter percutaneously into a hepatic vein and then wedging it into the liver. This wedged pressure reflects portal vein pressure. (An exception is portal vein thrombosis; in this case, the pressure is normal despite portal hypertension.)
Ursodeoxycholic acid helps prevent graft-vs-host disease in bone marrow or hematopoietic cell transplant recipients. Management includes withdrawing the causative agent (such as herbal teas) and providing supportive therapy. Most patients have mild to moderate disease and do quite well. Those that progress may require transjugular intrahepatic portosystemic shunting (TIPS) for relief of portal hypertension. However, in 25%, veno-occlusive disease is severe, accompanied by fulminant liver failure. Liver transplantation is a last resort.
Last full review/revision December 2007 by Eldon A. Shaffer, MD
Content last modified February 2012