Budd Chiari Syndrome

Budd-Chiari syndrome (BCS) is often categorized by disease duration and severity:[8][9]

Acute: Clinical manifestations develop rapidly over a few weeks, with intractable ascites and hepatic necrosis. Venous collaterals are not seen.

Subacute: Has insidious onset, with patients taking up to three months to develop symptoms. Venous collaterals develop, leading to minimal ascites and hepatic necrosis.

Chronic: Patients present with complications of cirrhosis. Venous collaterals are present.

Fulminant liver failure can occur in patients with BCS and is characterized by acute liver injury along with elevated transaminases, jaundice, elevated prothrombin time/international normalized ratio (PT/INR), and hepatic encephalopathy; the latter usually develops within eight weeks of the development of jaundice. Venous collaterals are not seen.

The majority of patients with Budd-Chiari syndrome present with the triad of abdominal pain, ascites, and hepatomegaly. Due to the non-specific nature of findings and a wide range of presentations, a high degree of suspicion is needed to diagnose this condition.

Clinical presentation: 

Acute and subacute presentation: Sudden onset of ascites, abdominal pain, jaundice, hepatomegaly, renal failure, hepatic encephalopathy.

Chronic presentation (most common): Progressive ascites and absence of jaundice. Half of the patients can present with renal impairment.

Rare presentation: Tender hepatomegaly, fulminant/sub-fulminant hepatic failure, jaundice, and renal failure.

 On physical examination, the following findings can be seen:

• Jaundice
• Ascites
• Hepatomegaly
• Splenomegaly
• Pedal edema
• Stasis ulcerations

BCS should be suspected when there is:

(1) Sudden onset of ascites and painful hepatomegaly

(2) Massive ascites with relatively normal liver functions

(3) Sinusoidal dilation in liver biopsy without heart disease

(4) Fulminant hepatic failure along with hepatomegaly and ascites

(5) Unexplained chronic liver disease

(6) Liver disease with a thrombogenic disorder.[6]

There is no individual test that establishes the diagnosis of Budd-Chiari syndrome. The diagnosis is based on classic clinical manifestations and conditions predisposing to thrombosis, such as the presence of malignancy.

Doppler ultrasonography is the initial test of choice and usually helps in confirming the diagnosis. If it is unavailable, equivocal, or cannot be performed, computed tomography (CT) or magnetic resonance imaging (MRI) may be helpful. If these tests fail to establish a diagnosis, but suspicion is still high, venography may be helpful.

 Diagnostic paracentesis:

• Examination of ascitic fluid provides invaluable clues to diagnosis and form of presentation.
• Elevated protein levels >2g/d and a white blood cell count (WBC) < 500/microliter are mostly present in patients with the chronic form.
• The serum ascites-albumin gradient is usually <1.1 g/dl in the chronic form in comparison to patients with an acute form of the syndrome.

Blood / biochemical abnormalities:

Non-specific except for mild elevation in serum aminotransferases (ALT/AST) and alkaline phosphatase level in 25-50% patients

Radiological evaluation:

• Ultrasonography, preferably, the color flow doppler, can visualize the thrombi with a sensitivity and specificity of 85-90%.[10]
• CT scanning is helpful if a mechanical obstruction is suspected as an underlying cause
• MRI is becoming the non-invasive modality of choice with a sensitivity and specificity of >90%.[11]
• Venography can accurately show the site and severity of obstruction, but the invasive nature limits the usefulness of the test.

Liver biopsy: while liver biopsy can be used for the diagnosis of Budd-Chiari syndrome, there are more non-invasive methods available. Liver biopsy often shows necrosis, hemorrhage, and congestion in the central zone.

The treatment of Budd-Chiari syndrome is focused on alleviating the obstruction, preventing the progression of the clot, limiting progressive liver injury, and preventing or managing complications.

Goals of treatment: 

• Relieving obstruction 

• Correcting underlying conditions 

• Monitoring liver deterioration

 Treatment of Budd-Chiari syndrome:

• Anticoagulants are the mainstay of treatment. They are started initially with low-molecular-weight heparin and then transitioned to warfarin, which is continued lifelong. PT/INR should be monitored and should be kept in the therapeutic range for patients on warfarin.
• Other treatment options include thrombolysis and stenting, as well as placement of a transjugular intrahepatic portosystemic shunt in acute forms of BCS, which fail to respond.
• Surgical decompression can also be considered in acute forms if other therapies fail.

Liver transplantation: In patients who fail all therapies or who have developed decompensated cirrhosis, liver transplantation may be an option. The ten-year survival rate ranges from 69-84% as per two reported studies.[12][13]

Differential diagnosis of Budd Chiari syndrome includes the following:

• Right-sided heart failure
• Metastatic liver disease
• Alcoholic liver disease
• Granulomatous liver disease
• Alpha-1 antitrypsin deficiency
• Infectious hepatitis
• Fitz-Hugh Curtis syndrome
• Congestive heart failure
• Niemann-Pick disease type C
• Infectious hepatitis
• Neonatal hemochromatosis
• Biliary atresia
• Congenital hepatic fibrosis
• Cystic fibrosis
• Inborn errors of metabolism
• Hemochromatosis
• Drug-induced hepatitis

Factors contributing to a good prognosis for Budd-Chiari syndrome are:

• Younger age
• Low Child-Pugh score
• Low creatinine level in serum
• Absence of ascites

Factors contributing to a bad prognosis:

• Involvement of all three hepatic veins and/or portal vein
• Presence of ascites
• Older age at the time of presentation
• High Child-Pugh score
• Chronic disease at presentation[14][15][16]

Complications of Budd-Chiari syndrome are mostly related to underlying conditions and degree of liver failure.

In general, untreated Budd-Chiari syndrome can lead to the following:

• Hepatic encephalopathy
• Variceal hemorrhage
• Hepatorenal syndrome
• Portal hypertension
• Bacterial peritonitis in the presence of ascites
• Heptocellular carcinoma

There is a need to educate patients, especially those with risk factors, regarding the possibility of this condition. Basic education regarding symptoms consistent with liver abnormalities should be taught. Patients should be advised to seek a professional opinion if they begin to develop symptoms. More importantly, regular follow up with their clinicians should be encouraged.

Clinicians need to have a high clinical suspicion for this condition in patients with risk factors.

Treatment of this condition requires an interprofessional team consisting of hepatologist/gastroenterologist, hematologist, vascular surgeon, transplant hepatologist, interventional radiologist, and transplant surgeon.

A hematologist might be consulted for an opinion regarding underlying hematologic condition if no other predisposing condition is evident.

In those with acute liver failure, admission, and management in an intensive care unit (ICU) is warranted, with evaluation by a vascular surgeon, transplant hepatologist, interventional radiologist, and transplant surgeon. A liver transplant should be considered.[17] [Level 3]

In patients with an acute form with an identifiable clot, thrombolytic therapy is advisable.[18] [Level 5]

Routine stenting with angioplasty was found to be superior to angioplasty only for preventing restenosis in one study.[19] [Level 2]

Once the condition has resolved, patients should be counseled regarding the need for continuing lifelong anticoagulation and proper follow-up.