Secondary Budd–Chiari syndrome : compression of the hepatic vein by an outside structure
Budd–Chiari syndrome is also seen in tuberculosis, congenital venous webs and occasionally in inferior vena caval stenosis. Often, the patient is known to have a tendency towards thrombosis, although Budd–Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic tendencies include protein C deficiency, protein S deficiency, the Factor V Leiden mutation, hereditary anti-thrombin deficiency and prothrombin mutation G20210A. An important non-genetic risk factor is the use of estrogen-containing forms of hormonal contraception. Other risk factors include the antiphospholipid syndrome, aspergillosis, Behçet's disease, dacarbazine, pregnancy, and trauma. Many patients have Budd–Chiari syndrome as a complication of polycythemia vera. People who have paroxysmal nocturnal hemoglobinuria appear to be especially at risk for Budd–Chiari syndrome, more than other forms of thrombophilia: up to 39% develop venous thromboses, and 12% may acquire Budd-Chiari. A related condition is veno-occlusive disease, which occurs in recipients of bone marrow transplants as a complication of their medication. Although its mechanism is similar, it is not considered a form of Budd–Chiari syndrome. Other toxicologic causes of veno-occlusive disease include plant & herbal sources of pyrrolizidine alkaloids such as Borage, Boneset, Coltsfoot, T'u-san-chi, Comfrey, Heliotrope, Gordolobo, Germander, and Chaparral.
Pathophysiology
Any obstruction of the venous vasculature of the liver is referred to as Budd–Chiari syndrome, from the venules to the right atrium. This leads to increased portal vein and hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure causes increased filtration of vascular fluid with the formation of ascites in the abdomen and collateral venous flow through alternative veins leading to esophageal, gastric and rectal varices. Obstruction also causes centrilobular necrosis and peripheral lobule fatty change due to ischemia. If this condition persists chronically what is known as nutmeg liver will develop. Kidney failure may occur, perhaps due to the body sensing an "underfill" state and subsequent activation of the renin-angiotensin pathways and excess sodium retention.
Diagnosis
When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers. Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography or magnetic resonance imaging is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reye's syndrome. Evaluation for a JAK2 V617F mutation is recommended.
Treatment
A minority of patients can be treated medically with sodium restriction, diuretics to control ascites, anticoagulants such as heparin and warfarin, and general symptomatic management. The majority of patients require further intervention. Milder forms of Budd–Chiari may be treated with surgical shunts to divert blood flow around the obstruction or the liver itself. Shunts must be placed early after diagnosis for best results. The TIPS is similar to a surgical shunt: it accomplishes the same goal but has a lower procedure-related mortality—a factor that has led to a growth in its popularity. If all the hepatic veins are blocked, the portal vein can be approached via the intrahepatic part of inferior vena cava, a procedure called DIPS. Patients with stenosis or vena caval obstruction may benefit from angioplasty. Limited studies on thrombolysis with direct infusion of urokinase and tissue plasminogen activator into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted. Liver transplantation is an effective treatment for Budd–Chiari. It is generally reserved for patients with fulminant liver failure, failure of shunts or progression of cirrhosis that reduces the life expectancy to 1 year. Long-term survival after transplantation ranges from 69–87%. The most common complications of transplant include rejection, arterial or venous thromboses and bleeding due to anticoagulation. Up to 10% of patients may have a recurrence of Budd–Chiari syndrome after the transplant.
Prognosis
Several studies have attempted to predict the survival of patients with Budd–Chiari syndrome. In general, nearly 2/3 of patients with Budd–Chiari are alive at 10 years. Important negative prognostic indicators include ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, and altered serum levels of various substances. Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, a patient with an underlying myeloproliferative disorder may progress to acute leukemia, independently of Budd–Chiari syndrome.
Eponym
It is named after George Budd, a British physician, and Hans Chiari, an Austrian pathologist.
