Budd-Chiari Syndrome - Symptoms, Causes, Prevention, and Treatment

Budd chiari syndrome, the occlusion of hepatic veins (Obstruction of back flow of blood from liver to heart due to blockage) is an unusual condition which may be manifested by pain in the abdomen, ascites (build-up of fluid in the abdomen), hepatomegaly (liver enlargement) and a poor prognosis.

Anywhere throughout the vein's path, from the hepatic venules to the inferior vena cava (large vein that carry deoxygenated blood) junction and the right atrium (heart chamber), the obstruction could be thrombotic (related to blood clot) or non-thrombotic.

This disorder is an uncommon ailment considering its occurrence in 1 of 100000 individuals. In medical language Budd chiari syndrome is also known as hepatic venous outflow obstruction (HVOO).

Budd chiari syndrome is a diverse clinical disorder that can either be fatal if left untreated or may be managed with efficient treatment. When managed appropriately, the patients' prognosis is acceptable when compared to other chronic liver illnesses. Budd chiari syndrome can aggravate several conditions, including hematologic or malignant diseases, making it a rare significant syndrome.

Budd Chiari syndrome definition

Budd-Chiari syndrome is a rare liver condition that is defined as, obstruction to the outflow of blood in hepatic veins at any point, ranging from the small hepatic vein to the junction of the right atrium (heart chamber) and inferior vena cava (largest vein in the body carrying deoxygenated blood).

Budd chiari syndrome meaning

The phrase "Budd-Chiari" was first used in the late 1800s in reference to the eminent work of internist George Budd a British physician and Austrian pathologist Hans Chiari.

A brief report on three patients who experienced hepatic vein blockage was published by George Budd in 1845. The illness, which has never been documented before, was linked to alcoholism and sepsis. 53 years later, Hans Chiari proposed the theory that syphilis was the reason for the hepatic vein blockage, adding pathological and clinical connections to the discussion postulated by George Budd.

Hepatic venous outflow obstruction meaning

Hepatic venous outflow obstruction is a union of 4 words in which. 

• ‘Hepatic’- ‘hepatic’ is taken from latin word ‘hepaticus’ which means ‘pertaining to liver’
• ‘Venous’- ‘venous’ is derived from latin word ‘venosus’ that is used to describe ‘full of veins’
• ‘Outflow’- The word ‘outflow’ is derived from the Middle English word ‘outflowen’ which means ‘act or fact of flowing out’
• ‘Obstruction’- ‘obstruction’ is derived from latin word ‘obstructionem’ that is used to ‘express action of blocking up a way or passage’
  

Prevalence of Budd-Chiari syndrome

With a low incidence and prevalence in the general population, budd-chiari syndrome is an atypical serious liver condition. The incidence recorded in the literature varies from 0.2 to 4.1 cases per 10 lakh people annually, with an estimated prevalence of 1.4–4.0 cases per 10 lakh people in Western countries and 2.4–7.7 cases per million people in Asian countries. In Western studies, the prevalence was higher in women (52–69%), whereas in Asian studies, men were more often affected (48–70%).

Prevalence of budd chiari syndrome in India 

Budd chiari syndrome has higher prevalence in developing countries like India.

• A study demonstrated that between 1967 and 2000, five investigations were conducted in India, and the results showed a prevalence that ranged from 3.8 to 21.5%.
• Another study of 2024 stated that, in India, it is believed that up to 7.4% of children suffering from chronic liver illness could have budd-chiari syndrome.
  

Types of Budd-Chiari syndrome

Based on the location where the obstructive lesion is originated, Budd Chiari syndrome can be categorized into two types they are:

• Primary: In cases when endoluminal venous lesion-like thrombosis is the cause of blockage, primary budd chiari syndrome is taken into consideration.
  
• Secondary: when the cause arises from nearby structures such as extrinsic compression or tumor invasion, it is considered as secondary budd chiari syndrome.
  

Budd-Chiari syndrome signs and symptoms

Depending on whether the obstruction happens suddenly or gradually, various signs and symptoms may be experienced which may include:

• Pain in the upper right part of the abdomen
• Enlarged liver (hepatomegaly)
• Yellowing of the skin and the whites of the eyes (jaundice)
• Increased blood pressure in the veins carrying blood from the gastrointestinal (GI) tract back to the heart through the liver (portal hypertension)
• Enlarged veins in the abdomen
• Vomiting
• Fatigue 
• Ankle edema (swelling of ankles and foot due to fluid buildup)
• Statis ulcerations (sores that develop on foot)
  

Budd-Chiari syndrome causes

Budd-Chiari syndrome develops because of an underlying etiology in 80% of instances. These instances are primarily associated with a hypercoagulable state (a condition that increases the risk of blood clotting). The predominant causes of budd-chiari syndrome include: 

• Thrombosis (blood clot with complete or partial blockage)
• Myeloproliferative disorders (blood cancers that result in an excessive production of blood cells in the body)
• Malignancy (the existence of cancerous cells with the potential to spread to different parts of the body)
• Liver lesions (abnormal cell growth in the liver that may be cancerous or non-cancerous)
• Pregnancy and use of oral contraceptive pills
• Idiopathic (disease with no identifiable cause)
• Gastric diseases

Thrombosis (blood clot with complete or partial blockage)

Hepatic vein blockage is primarily caused by thrombosis. Venous thrombosis, especially hepatic vein thrombosis, requires the coexistence of one or more thrombogenic (prone to blood clot formation) diseases and a triggering stimulus. The majority of budd chiari syndrome patients have a medical condition that makes them more susceptible to blood clotting.

Myeloproliferative disorders (blood cancers that result in an excessive production of blood cells in the body)

The primary cause of hepatic vein thrombosis is myeloproliferative disorders. Since some myeloproliferative illnesses, such as polycythemia vera (blood cancer) and essential thrombocythemia (blood cancer that increase platelet count), are invariably associated with hypercoagulability (condition that increases the risk of blood clotting), these conditions are linked to about half of the cases of Budd-Chiari syndrome.

Malignancy (the existence of cancerous cells with the potential to spread to different parts of the body)

Malignancy is linked to 10% of cases of Budd-Chiari syndrome, and it either directly compresses or invades blood vessels. Malignancy accompanied by hypercoagulability cause venous thrombosis and blockage. Other types of cancers that are more predominant to cause Budd Chiari syndrome include:

• Hepatocellular carcinoma (liver cancer)
• Adrenal gland carcinoma (adrenal gland cancer)
• Renal cell carcinoma (kidney cancer)
• Leiomyosarcoma (cancer of smooth muscles in the body)
• Right atrial myxoma (cancer of right atrium [heart chamber])
• Wilms tumour (rare kidney cancer predominantly occurs in children)

Liver lesions (abnormal cell growth in the liver that may be cancerous or non-cancerous)

Compression of the vasculature can occasionally result from an infection or a lesion that takes up space in the liver. liver lesions can give rise to this disorder due to:

• Hepatic cysts (fluid filled sacs on liver)
• Adenomas (non-cancerous tumors)
• Cystadenomas (cancerous or non-cancerous tumors that occur in different body parts)
• Invasive aspergillosis (infection caused by fungus)
• Aortic aneurysms (bulge in blood vessel named aorta)

Pregnancy and use of oral contraceptive pills

An increased risk of budd chiari syndrome is associated with the use of oral contraceptives, especially those with a high estrogen level. Several reports states that patients in whom budd chiari syndrome was occurred due to oral contraceptives or pregnancy, may also have an underlying thrombophilia, either acquired or inherited.

Idiopathic (disease with no identifiable cause)

It is demonstrated that 20% cases of budd chiari syndrome occur due to unknown cause.

Gastric diseases

Studies have demonstrated that when underlying thrombophilias (condition that cause blood clots formation too easily) are present, budd chiari syndrome may be caused by ulcerative colitis, celiac disease, or abdominal trauma.

Budd-Chiari syndrome, may be caused by additional hypercoagulable conditions, such as:

• Bechet's disease: (an unusual condition that makes blood vessels inflamed)
  
• Polycystic kidney disease: (a genetic condition where fluid filled sacs are formed on the kidney)
• Factor V Leiden: (a disorder that increase the risk of developing clots due to mutation in the blood clotting factor V).
  

Several risk factors have been linked to Budd-Chiari Syndrome, which may raise the chances of developing the disorder. Some of them include:

• Oral contraceptives administration: Those who use estrogen-containing oral contraceptives have a twofold greater risk of developing budd chiari syndrome. In individuals with various thrombogenic diseases, oral contraceptives seem to mainly increase the risk of thrombosis. 
• Trauma: In case of severe traumatic instances, the veins over the liver may burst and this may result in a dramatic consequence of developing a syndrome (group of symptoms).
• Inflammatory diseases: people with inflammatory disorders such as inflammatory bowel disease, behchet’s disease etc are at a greater risk for developing thromboembolic complications which may eventually lead to budd chiari syndrome.
• Corona virus disease (COVID-19): A 2023 study had demonstrated that budd chiari syndrome is an uncommon and serious condition that can result from inflammatory and coagulation disorders associated with coronavirus disease 2019 (COVID-19)
• Cancers: several cancers such as hepatocellular carcinoma etc may have the tendency to cause budd chiari syndrome through invasion of venous outflow.
  

Budd-Chiari syndrome Complications

Budd-Chiari syndrome complications are primarily associated with the severity of liver failure and underlying medical problems. Untreated Budd-Chiari syndrome generally may have complications such as:

• Hepatic encephalopathy (the loss of brain function resulting from the liver's inability to eliminate toxins from the blood)
• Variceal haemorrhage (rupture of blood vessels located all over the digestive system)
• Hepatorenal syndrome (Kidney failure due to liver dysfunction)
• Portal hypertension (increased blood pressure in the vein that caries deoxygenated blood to liver from intestines)
• Bacterial peritonitis (infection of abdominal fluid) in the presence of ascites
• Hepatocellular carcinoma (liver cancer)