Excerpt from Budd-Chiari Syndrome

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Background

Budd-Chiari syndrome (BCS) is a manifestation of hepatic venous outflow obstruction that was first described by Budd in 1845 and then expounded upon by Chiari, who presented 13 cases in 1899. The hepatic outflow obstruction usually occurs at the level of the inferior vena cava (IVC); the hepatic veins; and, depending on the classification and nomenclature, possibly at the venule level.

The causes of BCS are numerous. There are 2 types of BCS: acute and chronic. The acute form results from an acute thrombosis of the main hepatic veins or the IVC. The chronic form is related to fibrosis of the intrahepatic veins, presumably related to inflammation. The classic presentation is with ascites, hepatomegaly, and abdominal pain.

Pathophysiology

In BCS, hepatic venous occlusion causes increased sinusoidal pressure, leading to a delay or reversal of portal venous blood inflow, ascites, and morphologic changes in the liver (resulting in abnormal liver function test results). Both the acute form and the chronic form of BCS result in severe centrilobular congestion and hepatocellular necrosis and atrophy. Two diseases that have clinical characteristics similar to those of BCS are severe right-sided heart failure and veno-occlusive disease of the liver. Hepatic veno-occlusive disease is characterized by inflammation of the postsinusoidal venules, which results in fibrosis and venous occlusion.

Membranous obstruction of the inferior vena cava (MOVC) is a rare clinical entity. The incidence of MOVC is higher in Japan and in Africa than it is in the United States and Europe. MOVC is a curable cause of a primary type of BCS, but MOVC is different from BCS in clinical manifestation and pathologic changes in the liver. Most patients with MOVC are cirrhotic and have ascites and esophageal varices.¹ 

BCS has been variously classified, with some investigators distinguishing between primary BCS (associated with IVC webs) and secondary BCS (ascribed to numerous causes, including tumor, thrombosis, and trauma). Still other authors categorize the disease according to the location of the obstruction, as follows:

• Type I disease - Occlusion of the IVC with or without secondary hepatic vein occlusion
• Type II disease - Occlusion of major hepatic veins
• Type III disease - Obstruction of the small centrilobular venules (considered by some authors as veno-occlusive disease)

The causes of BCS are numerous and include the following:

• Idiopathic: Historically, most cases of BCS considered idiopathic or congenital, although recent studies suggest the cause is unknown in only one third of cases
• Congenital: BCS caused by web, diaphragm, interruption of the IVC
• Venous thrombosis: BCS resulting from polycythemia rubra vera, antiphospholipid syndrome, pregnancy and the postpartum state, use of oral contraceptives, sickle cell disease, thrombocytosis, paroxysmal nocturnal hemoglobinuria
• Injury and/or inflammation: BCS caused by phlebitis, autoimmune disease (Behçet disease), trauma, radiation injury, use of immunosuppressive drugs and pyrrolizidine alkaloids
• Liver pathology: Fibrosis, hemorrhage, congestion causes of BCS
• Tumor: BCS caused by renal cell carcinoma, hepatocellular carcinoma, adrenal carcinoma, metastasis, leiomyosarcoma of the IVC

In most patients with BCS, hepatic venous outflow is not completely eliminated because accessory hepatic veins drain into the IVC above or below the site of obstruction. The most common accessory veins include the accessory inferior hepatic and caudate veins, which drain into the IVC inferior to the major hepatic veins. Vascular communications also exist via the azygos vein, the intercostal vessels, and the paravertebral veins, which provide alternative pathways for hepatic venous drainage in patients with BCS.

Intrahepatic communication between the hepatic and portal veins also establishes reversal of flow in some of the portal venous branches, although flow in the main portal vein tends to remain centripetal. Some of the hepatic venous drainage is preserved; the caudate lobe hypertrophies, sometimes massively, and it may produce secondary IVC obstruction. Other parts of the liver that have preserved venous drainage may also undergo hypertrophy.

Some venous drainage also occurs via the capsular veins, but this drainage is not sufficient to prevent peripheral atrophy in patients with BCS. Parts of the liver that have complete obstruction of venous drainage tend to drain via the portal vein branches, depriving involved parts of the liver of a portal venous blood supply; therefore, the trophic effects of hormones occur. Hepatic hypertrophy and regeneration always depend on the trophic effect of the portal blood supply. Thus, BCS typically is associated with peripheral atrophy of the liver and with caudate and central hypertrophy. On cross-sectional images, the porta hepatis may be displaced anteriorly in BCS. Concomitant portal vein thrombosis may be present in 9-20% of patients with BCS.²

Frequency

United States

Hematologic disorders, such as polycythemia rubra vera, paroxysmal nocturnal hemoglobinuria, and myeloproliferative diseases, account for 18% of the cases of BCS. A history of pregnancy or the postpartum state accounts for another 20%. Tumors account for 9%, while IVC webs account for most cases in patients from eastern Asia, India, and South Africa. Veno-occlusive disease is a complication in as many as 25% of patients treated with bone marrow transplantation.

International

Overall incidence of BCS is unknown.

Mortality/Morbidity

BCS is potentially life-threatening, depending on the extent and rapidity of hepatic venous obstruction. A high index of suspicion is necessary in order to make the diagnosis, because BCS can be very indolent or even asymptomatic.

• Prognosis is more favorable in patients with IVC webs but is extremely poor in patients with renal cell carcinoma, hepatocellular carcinoma, and adrenal tumors.
• Mortality is 83% in patients with veno-occlusive disease, but if BCS is diagnosed early, patients may respond to treatment such as anticoagulant therapy.
• Treatment procedures are high risk and are associated with different rates of morbidity and mortality.
• In a multicenter international investigation, Murad et al studied the determinants of survival and evaluated the use of portosystemic shunting in 237 patients with BCS.³. Overall survival at 1 year, 5 years, and 10 years was 82% (95% confidence interval [CI], 77-87%), 69% (95% CI, 62-76%), and 62% (95% CI, 54-70%), respectively. Independent determinants of survival were encephalopathy, ascites, prothrombin time, and bilirubin level. At the time of diagnosis, patients were classified into 3 prognostic classes on the basis of baseline clinical and laboratory parameters: good prognosis, class I; intermediate prognosis, class II; and poor prognosis, class III. The 5-year survival rate for BCS patients in class I was 89% (95% CI, 79-99%); for class II, 74% (95% CI, 65-83%); and for class III, 42% (95% CI, 28%-56%). Anticoagulants were given to 72% of patients, but this treatment improved survival only in class I patients (relative risk [RR], 0.14; 95% CI, 0.02-1.21). Portosystemic shunting was performed in 49% of the patients (n = 117). Improved survival with surgical portosystemic shunting occurred in class II BCS patients; time-dependent analyses showed improved survival only in these patients (RR, 0.63; 95% CI, 0.26-1.49). 
  

Race

The IVC web/diaphragm, believed to be either congenital or an acquired abnormality from long-standing IVC thrombosis, is a common cause of BCS in South Africa, India, Japan, and Korea but is rare in Europe and North America.

Sex

A slight female preponderance is seen in patients with BCS.

Age

Persons of any age can be affected, although hepatic veno-occlusive disease after bone marrow transplantation is more a disease of the young than a disease of older individuals.

Anatomy

Superior veins (right, middle, left) drain most of the liver. Typically, the superior veins are as large as 1 cm in diameter and pass obliquely back and upward to the IVC. Small veins drain the caudate and adjacent part of the right lobe directly to the IVC. Separate caudate lobe venous drainage may allow preservation of caudate lobe function in hepatic vein obstruction.

Flow in the hepatic veins is complex because it is affected directly by flow and pressure changes in the right atrium and IVC. Throughout the greater part of the cardiac cycle, flow is toward the heart (ie, away from the ultrasound [US] probe on the anterior abdominal wall). Forward flow toward the heart is reduced during right atrial systole as the pressure of right atrial contraction is carried back to the IVC and hepatic veins.

After right atrial systole, a brief increase in hepatic vein flow occurs, followed by a pressure wave caused by sudden tricuspid valve closure at the start of ventricular systole. The pressure wave caused by tricuspid closure may result in transient reversal of normal hepatic vein flow. The reversal of flow indicates that the liver is soft and compliant and can accommodate transient flow reversal.

Hepatic parenchymal disease may increase hepatic rigidity, reducing compliance and preventing flow reversal. A rough correlation exists between the degree of flattening of the hepatic vein waveform and the degree of severity of hepatic parenchymal disease. Cardiac disease may affect the hepatic venous waveform, usually increasing the waveform pulsatility, but the effect depends on the nature of cardiac disease and the presence or absence of hepatic parenchymal disease.

Hepatic disease that increases hepatic rigidity reduces the effect of cardiac disease on the hepatic venous waveform. Prolonged or sudden severe IVC or hepatic venous congestion may cause hepatomegaly and jaundice. When the hepatic parenchyma is abnormally rigid, abnormal cardiac waveforms may be masked by reduced hepatic compliance.

Maximum diameters of the main trunk right hepatic vein are 6.2 mm ± 1.43 in healthy men and 5.6 mm ± 1.66 in healthy women.

Clinical Details

• Patients present with painful hepatomegaly and diuretic-resistant ascites.
• Features of portal hypertension and variceal bleeding occur later.
• Approximately 25% of patients with BCS present acutely, and the remainder of patients present with subacute or chronic disease.
• In addition to abdominal pain, patients also may present with lower limb edema and distended abdominal veins.
• Splenomegaly and jaundice are recorded in as many as 25% of patients.
• In the less common acute form, rapid onset of abdominal pain, vomiting, hepatomegaly, and jaundice occur, often in the setting of a known renal or hepatic tumor or the setting of bone marrow transplantation and a patient on chemotherapy.
• Biochemical findings include elevation of transaminase and serum alkaline phosphatase levels with only a slight elevation of bilirubin levels. The prothrombin time may be prolonged.

Preferred Examination

On the whole, plain radiography has little to offer in the diagnosis of BCS.

Sonography is noninvasive and has high sensitivity and specificity. Sonographic images easily depict the echogenic membrane or fibrous cord in the IVC, which is a common cause of chronic BCS.

CT scanning and MRI are making inroads, but diagnostic features are seen in only a minority of patients, although the cross-sectional images are superior and are vital in planning intervention.

Radionuclide scanning is an elegant and noninvasive technique; however, its findings are nonspecific.

Angiography, although invasive, is the criterion standard. This examination may have to be performed, particularly in patients in whom an IVC abnormality is suspected and when radiologic intervention is planned.

The key imaging findings in BCS, including those of CT, MRI, US, and angiography, are occlusion of the hepatic veins, the inferior vena cava, or both; caudate lobe enlargement; inhomogeneous liver enhancement; and the presence of intrahepatic collateral vessels and hypervascular nodules. Awareness of these findings is important for early diagnosis and appropriate treatment.⁴

Limitations of Techniques

All findings from cross-sectional imaging are nonspecific. Both false-positive and false-negative diagnoses may occur, although this limitation applies less to angiographic studies than to other tests.

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