Budd-Chiari Syndrome - Causes, Symptoms and Treatment

Introduction:

Budd-Chiari syndrome is a rare complication named after British physician George Budd and Austrian pathologist Hans Chiari. It is characterized by obstruction of the outflow in the hepatic veins (veins that carry deoxygenated blood from the liver to the heart). It occurs in one in a million of the general population. The clinical manifestations are nonspecific, and imaging may be difficult in the early stages. Generally, obstruction of a single hepatic vein is not evident clinically, and the clinical manifestations are seen when two veins are blocked. However, if left untreated, the condition may become fatal.

What Is Budd-Chiari Syndrome (BCS)?

The liver has many functions that include filtering all the blood in the body. When the outflow of blood is blocked fully or partially, it results in Budd-Chiari syndrome. The obstruction could be thrombotic (blood clots inside the blood vessel) or non-thrombotic, occurring anywhere between the hepatic vein to the inferior vena cava or the right atrium. This can result in high blood pressure of the portal vein, known as portal hypertension. This causes reduced hepatic perfusion, which eventually results in liver congestion. Then the blood flow to the liver cells is reduced, leading to an injury of the liver cells followed by the death of the liver cells. It is followed by progressive fibrosis or scarring and ultimately liver cirrhosis or liver failure.

What Causes Budd-Chiari Syndrome?

BCS occurs commonly in women and young adults. It could be primary or secondary, depending on the origin of the obstructive lesion. If the obstruction is due to the hepatic venous lesion like a thrombosis, it is considered a primary BCS. If the block is due to tumor invasion or extrinsic causes, then it is a secondary BCS. Thrombosis is the primary cause of hepatic vein obstruction. Other causes include:

1. Hematologic diseases, especially myeloproliferative disorders.

2. Thrombotic diseases include paroxysmal nocturnal hemoglobinuria (characterized by destruction of red blood cells), antiphospholipid syndrome (disorder in which the immune system mistakenly affects the normal proteins), etc.

3. Metastatic invasion.

4. Membranous web-like obstruction of the hepatic vein.

5. Interruption of the diaphragm, which is congenital.

6. Behcet’s disease.

7. The use of oral contraceptives or pregnancy.

8. Abdominal trauma.

9. Infections such as tuberculosis, syphilis, aspergillosis.

10. Plant or herbal sources of pyrrolizidine alkaloids are toxic.

11. Protein S deficiency.

12. Leiomyosarcoma of inferior vena cava.

13. Sickle cell disease.

14. Polycythemia vera (type of blood cancer where there are excess red blood cells).

15. Immunosuppressant drugs.

What Are the Signs and Symptoms?

The clinical signs and symptoms in the patient depend upon the extent and acuteness of the hepatic venous obstruction. BCS includes the following signs and symptoms:

• Severe upper abdominal pain.

• Jaundice.

• Liver enlargement.

• Spleen enlargement.

• Fluid accumulation within the peritoneal cavity (ascites).

• Elevated liver enzymes.

• Encephalopathy (damage to the brain).

• Severe lactic acidosis.

How to Diagnose Budd-Chiari Syndrome?

Doppler ultrasonography of the liver, computed tomography(CT), magnetic resonance imaging (MRI), hepatic venography, metabolic function tests, cavograms, and liver biopsy are available diagnostic methods. The liver biopsy shows high-grade venous congestion, centrilobular liver cell atrophy, and thrombi within the terminal hepatic venules. Diagnosis can be based on the following:

• Abrupt onset of ascites (fluid in the abdomen) and painful hepatomegaly (enlarged liver).

• Massive ascites with preserved liver functions. On examination of the ascitic fluid in chronic patients, they usually have a high protein concentration (greater than two g/dL). The serum ascites-albumin gradient is generally less than 1.1.

• Sinusoidal dilation in liver biopsy without heart disease.

• Fulminant hepatic failure is associated with hepatomegaly and ascites.

• Unexplained chronic liver disease.

• Liver disease with a blood clotting disorder.

• WBC (white blood cell) count is usually less than 500 per microlitre.

Ultrasound -

In acute cases, hepatomegaly, splenomegaly, and heterogeneous echotexture are present. There will be peripheral atrophy of the affected regions, regenerative nodules, gallbladder wall thickening, and ascites in chronic cases.

Color Doppler -

The following findings are seen in the color Doppler test:

1. No flow or inappropriately directed flow in the right hepatic vein.

2. The discontinuity between the central hepatic vein and the inferior vena cava. Reversed flow in hepatic veins.

3. Intra and extrahepatic collaterals, low or absent flow in the inferior vena cava. The high resistive index within the hepatic artery, tumor thrombus within the inferior vena cava.

Computed Tomography(CT) Findings -

1. The early enhancement of the caudate lobe (only part of the liver that is in contact with the inferior vena cava) and central liver,

2. Delayed enhancement of the peripheral liver with accompanying low central density (flip-flop appearance),

3. Nutmeg liver (inhomogeneous mottled liver),

4. Inability to identify hepatic veins.

Angiography Findings -

On hepatic venography, complete occlusion of hepatic vein(s) may be noted, which may or may not be associated with narrowing of the intrahepatic inferior vena cava.

What Are the Treatment Options Available?

The primary goal of the treatment should be to improve hepatic perfusion and preserve the functioning of the hepatic cells.

Medical Treatment -

It includes anticoagulant therapy- intravenous Heparin initially and then by Warfarin orally. Other measures to control ascites and gastrointestinal bleeding are taken. This includes reducing the salt intake in the diet, using diuretics such as Spironolactone and Furosemide. In the case of refractory ascites, large-volume paracentesis with albumin infusion is done. Normal serum albumin and bilirubin level indicate an improvement in liver functions. Thus liver function tests help evaluate the effectiveness of therapy. The medical treatment may alleviate the patient’s symptoms temporarily, but the disease progresses.

Surgical Treatment -

This includes:

• Balloon angioplasty.

• Localized thrombolysis.

• Variceal treatment.

• Portal decompression.

• Percutaneous transhepatic balloon angioplasty (PTBA).

• Surgical shunts may be placed to divert the blood flow around the obstruction of the liver. The TIPS (transjugular intrahepatic portosystemic shunts) can be employed. If all the hepatic veins are blocked, the portal veins can be approached by the intrahepatic part of the inferior vena cava. This procedure is called DIPS (direct intrahepatic portocaval shunt).

• Liver transplantation is generally performed in the case of fulminant liver failure when the shunts fail.

What Are the Complications?

• Cirrhosis of the liver.

• Ascites (fluid build-up in the abdomen).

• Varicose veins in the esophagus.

• Graft infection, rejection, arterial or venous thrombosis.

• Gallbladder, kidney problems.

• Low liver function can affect digestion.

• Patients with chronic Budd-Chiari syndrome are at risk for hepatocellular carcinoma and should be monitored with serum alpha-fetoprotein.

Conclusion:

The survival of the patient with Budd-Chiari syndrome is mainly dependent on the underlying cause. In general, nearly two-thirds of the patients survive for ten years. Some negative prognostic indicators like ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, etc., indicate the patient's prognosis.