Budd Chiari Syndrome

Introduction

Budd-Chiari syndrome (BCS) is a rare disorder caused as a result of impaired hepatic venous outflow at any point between the small hepatic veins and the inferior vena cava. Some authors exclude veno-occlusive disease as a type of Budd Chiari syndrome, where the obstruction is at the level of the sinusoids and terminal hepatic venules (Nobre et al, 2017). Primary Budd-Chiari syndrome is defined as obstruction due to a predominantly venous process (thrombosis or phlebitis). In contrast, secondary Budd-Chiari syndrome is defined as compression or invasion of the hepatic veins and/or the inferior vena cava by a lesion that originates outside the vein(for example, a malignancy).

• Obstruction to blood flow
• Venous stasis
• Congestive hepatopathy
• Increased sinusoidal pressure with hepatic sinusoidal thrombosis
• Hepatic ischemia
• Necrosis of hepatocytes especially in perivenular zones
• Hepatic fibrosis
• Portal hypertension

History:

The syndrome was first described in 1845 by an English physician named George Budd, who defined a triad associated with this disease as abdominal pain, ascites, and hepatomegaly. However, it was not until 1899 when Austrian pathologist Hans Chiari described its histopathology.

Classification:

Budd Chiari syndrome can be classified on the basis of etiology (primary or secondary), clinical course (acute or subacute or chronic), and morphology (truncal, radicular, and venooclusive type).

On the basis of etiology:

1. Primary BCS - occurs in patients who have an underlying hematological disorder or hypercoagulable state. These can include myeloproliferative disorders, polycythemia vera, essential thrombocytemia, or primary myelofibrosis (Zhang and Li, 2007). The most common primary hypercoagulable conditions in these patients are mutations of factor V Leiden, factor II (prothrombin), JAK-2 tyrosine kinase genes and antiphospholipid syndrome (Colaizzo et al., 2008).
2. Secondary BCS - is due to any disease that causes obstruction by invasion or compression of the Inferior vena cava or hepatic vein leading to their consequent thrombosis. This includes focal liver lesions (hepatocellular carcinoma, liver abscess, cyst), renal or adrenal adenocarcinoma, blunt abdominal trauma, and rarely primary sarcomas of IVC or myxoma of the right atrium (Mukund and Gamanagatti, 2011).

On the basis of clinical course:

Budd-Chiari syndrome (BCS) is often categorized by disease duration and severity:(Mennon, ferral)

1. Acute: Clinical manifestations develop rapidly over a few weeks, with intractable ascites and hepatic necrosis. Venous collaterals are not seen.
2. Subacute: Has insidious onset, with patients taking up to three months to develop symptoms. Venous collaterals develop, leading to minimal ascites and hepatic necrosis.
3. Chronic: Patients present with complications of cirrhosis. Venous collaterals are present.

On the basis of location of the obstruction:

1. truncal type - with obstruction of the IVC (±HV), 2. radicular type - with obstruction of HV, 3. venoocclusive type - with obstruction of small centrilobular veins (Lambert, 2016).

Prevelance:

Budd Chiari syndrome is relatively uncommon in the pediatric age group. In India the prevalence of BCS as a cause of paediatric chronic liver disease is estimated as 7.4% (Alam et al, 2014). In non- Asian countries, Budd-Chiari Syndrome is usually diagnosed in the third or fourth decade of life, predominantly in females. It is most commonly due to hepatic vein blockage. In Asian countries, it is more common in males,and the most common cause is inferior vena cava blockage or a combination of inferior vena cava and hepatic vein blockage.

Clinical features: (stat pearls, 2021)

Acute presentation: clinical manifestations develop rapidly over a few weeks, with intractactable ascites and hepatic necrosis leading to abdominal pain, jaundice, hepatomegaly, renal failure, hepatic encephalopathy. Venous collaterals are not seen.

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

Chronic presentation (most common): Progressive ascites and absence of jaundice, patients present with complications of cirrhosis. Almost 50% of the patients can present with renal impairment.

Rare presentation: Tender hepatomegaly, fulminant hepatic failure and renal failure.

BCS should be suspected in case of: (Aydinli et al, 2007)

1. Sudden onset ascites with painful hepatomegaly
2. Massive ascites with relatively normal liver functionsSinusoidal dilation in liver biopsy without heart disease
3. Fulminant hepatic failure along with hepatomegaly and ascites
4. Unexplained chronic liver disease
5. Liver disease with a prothrombotic disorder.
6. Studies have shown that site of the block does not cause any difference in the clinical presentation (Madangopalan et al).

The most common lobe affected in Budd-Chiari Syndrome is the caudate lobe because its blood is directly shunted into the inferior vena cava. Hence when the hepatic veins are occluded, the caudate lobe undergoes hypertrophy.

Diagnosis:

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/ microlitre are mostly present in patients with the chronic form.

• The serum ascites -albumin gradient is usually<1.1g/dl in the chronic form compared to patients with an acute form of the syndrome.

Imaging is the mainstay of diagnosis, by demonstrating obstruction of Inferior vena cava, hepatic vein or portal venous system, or a secondary pathology.

Ultrasound is a first-line method with high sensitivity and specificity of up to 85% (Bolondi et al., 1991). Venous outflow obstruction is demonstrated by absent flow and echogenic content in the lumen. Blood flow in a stenosis becomes accelerated indicating turbulence. Ultrasound can also detect echotecture of the liver parenchyma (macronodular cirrhosis, focal liver lesions), hypertrophy of the caudate lobe (which is typical in Budd Chiari s yndrome), ascites, collateral blood flow, or direct invasion and compression of vessels by a mass.

Doppler USG established the diagnosis in 95% cases. A similarly high diagnostic accuracy (>80%) of Doppler has been shown by others [3,15].

Contrast-enhanced computed tomography (CT) is performed in portal venous phase in order to achieve good contrast filling in the vessels for optimal detection of their pathology. Inhomogeneous enhancement of the liver parenchyma results in mottled appearance with relative sparing of the caudate lobe and the peri-venous parenchyma that have separate venous drainage. These changes are more obvious on magnetic resonance (MR), which provides images with much better contrast (Zhou et al., 2014).

Invasive imaging methods that can be used to depict obstruction of the

venous outflow include venography of the inferior vena cava and hepatic veins. They are commonly used together with interventional procedures to restore patency of the vessels (venoplasty).

Liver biopsy is indicated in patients with suspected venoocclusive type (III) of BCS of unknown etiology, when macroscopic obstruction of the venous outflow has been excluded by imaging. Biopsy of the liver of the patient suffering from Budd-Chiari Syndrome shows the following features:

• Necrosis of hepatic cells in the centrilobular area
• Sinusoidal dilation due to stasis of blood flow
• Sometimes macro nodules can also be seen in this syndrome.

Laboratory tests must be done as part of the comprehensive workup of patients to diagnose hematological and coagulation disorders that may be recognized in up to 75% of patients (Singh et al., 2000). In 25% of patients, even two underlying conditions can be identified (Aydinli and Bayraktar, 2007). Primary BCS requires laboratory test for factor V Leiden and prothrombin mutations, for the presence of antiphospholipid antibodies

Management:

The recommended therapeutic approach to BCS is based on a stepwise algorithm beginning with: (Grus 2017)

1. Medical treatment (anticoagulant therapy with low molecular weight heparin or warfarin to prevent further thrombosis)
2. Endovascular treatment to restore vessel patency (venoplasty, stenting, and local thrombolysis)
3. Placement of transjugular portosystemic shunt (TIPS)
4. Orthotopic liver transplantation as a last resort rescue treatment in end stage liver disease.

Outcome:

If untreated, 70% of patients die within one year and 90% within three years, usually from complications of liver cirrhosis (Murad et al., 2004; Fu

et al., 2011).

Differential Diagnosis

• Right sided heart failure

• Metastatic liver disease

• Alcoholic liver disease

• Granulomatous liver disease

• Alpha-1 antitrypsin deficiency

• Infectious hepatitis

• Fitz-Hugh Curtis syndrome

• Cystic fibrosis

• Neonatal hemochromatosis

• Biliary atresia

• Inborn errors of metabolism