Budd-Chiari syndrome
Encyclopedia
In medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

 (gastroenterology
Gastroenterology
Gastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...

 and hepatology
Hepatology
Hepatology is the branch of medicine that incorporates the study of liver, gallbladder, biliary tree, and pancreas as well as management of their disorders. Etymologically the word Hepatology is formed of ancient Greek hepar or hepato- meaning ' liver' and suffix -logia meaning 'word' or 'speech'...

), Budd–Chiari syndrome is the clinical picture caused by occlusion
Vascular occlusion
Vascular occlusion is a sudden blockage of a blood vessel, usually with a clot. It differs from thrombosis in that it can be used to describe any form of blockage, not just one formed by a clot. When it occurs in a major vein, it can, in some cases, cause deep vein thrombosis. The condition is...

 of the hepatic veins. It presents with the classical triad of abdominal pain, ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

 and hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

. Examples of occlusion include thrombosis of hepatic veins. The syndrome can be fulminant, acute, chronic, or asymptomatic. It occurs in 1 out of a million individuals and is more common in females. Some 10-20% also have obstruction of the portal vein.

Signs and symptoms

The acute syndrome presents with rapidly progressive: severe upper abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

, jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

, hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

 (enlarged liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

), ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

, elevated liver enzymes, and eventually encephalopathy
Encephalopathy
Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...

. The fulminant syndrome presents early with encephalopathy and ascites. Severe hepatic necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

 and lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...

 may be present as well. Caudate lobe hypertrophy is often present. The majority of patients have a slower-onset form of Budd–Chiari syndrome. This can be painless. A system of venous collaterals may form around the occlusion which may be seen on imaging as a "spider's web." Patients may progress to cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

 and show the signs of liver failure.

An asymptomatic form may be totally silent and discovered only incidentally. It is generally not concerning.

Causes

  • The cause cannot be found in about half of the patients
  • Primary (75%): thrombosis
    Thrombosis
    Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...

     of the hepatic vein
  • Secondary (25%): compression of the hepatic vein by an outside structure (e.g. a tumor
    Tumor
    A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

    )
  • Hepatic vein thrombosis is associated with the following in decreasing order of frequency:
    (A)Polycythemia vera
    Polycythemia vera
    Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...

     
    (B)pregnancy
    (C)post partum state
    (D)use of oral contraceptive
    Oral contraceptive
    The combined oral contraceptive pill , often referred to as the birth-control pill or colloquially as "the Pill", is a birth control method that includes a combination of an estrogen and a progestin . When taken by mouth every day, these pills inhibit female fertility...

     
    (E)paroxysmal nocturnal hemoglobinuria
    Paroxysmal nocturnal hemoglobinuria
    Paroxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...

     
    (F)Hepatocellular carcinoma
    Hepatocellular carcinoma
    Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...

  • Infection such as TB
  • Congenital venous webs
  • Occasionally inferior vena caval stenosis


Often, the patient is known to have a tendency towards thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...

, although Budd–Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic tendencies include Protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...

 deficiency, Protein S
Protein S
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...

 deficiency, the Factor V Leiden
Factor V Leiden
Factor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...

 mutation, and Prothrombin Mutation G20210A. An important non-genetic risk factor is the use of estrogen-containing (combined) forms of hormonal contraception
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...

. Other risk factors include the antiphospholipid syndrome
Antiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...

, aspergillosis
Aspergillosis
Aspergillosis is the name given to a wide variety of diseases caused by fungi of the genus Aspergillus. The most common forms are allergic bronchopulmonary aspergillosis, pulmonary aspergilloma and invasive aspergillosis. Most humans inhale Aspergillus spores every day...

, Behçet's disease
Behçet's disease
Behçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements...

, dacarbazine
Dacarbazine
Dacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl...

, pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

, and trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

.

Many patients have Budd–Chiari syndrome as a complication of polycythemia vera
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...

 (myeloproliferative disease
Myeloproliferative disease
The myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...

 of red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

s). Patients suffering from paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...

 (PNH) appear to be especially at risk for Budd–Chiari syndrome, more than other forms of thrombophilia
Thrombophilia
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...

: 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 transplant
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...

s 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 (sunflower seeds), Gordolobo, Germander, and Chaparral.

Pathophysiology

Any obstruction of the venous
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...

 vasculature of the liver is referred to as Budd–Chiari syndrome, from the venule
Venule
A venule is a very small blood vessel in the microcirculation that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins. Venules range from 8 to 100μm in diameter and are formed when capillaries unite .Venules are blood vessels that drain blood...

s to the right atrium
Right atrium
The right atrium is one of four chambers in the hearts of mammals and archosaurs...

. This leads to increased portal vein and hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure causes: 1) increased filtration of vascular fluid with the formation of protein-rich ascites in the abdomen; and 2) collateral venous flow through alternative veins leading to oesophageal, 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
Nutmeg liver
In hepatology, congestive hepatopathy, also known as nutmeg liver and chronic passive congestion of the liver, is liver dysfunction due to venous congestion, usually cardiac dysfunction, i.e...

 will develop. Renal 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 (creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...

, urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

, electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

s, LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...

).

Budd–Chiari syndrome is most commonly diagnosed using ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

 studies of the abdomen
Abdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...

 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
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 (CT) or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy
Liver biopsy
Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...

 is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia
Galactosemia
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...

 or Reye's syndrome
Reye's syndrome
Reye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar . The classic features are liver damage, aspirin use and a viral infection...

.

Treatment

A minority of patient
s can be treated medically with sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 restriction, diuretics to control ascites, anticoagulants such as heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...

 and warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

, 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 transjugular intrahepatic portosystemic shunt
Transjugular intrahepatic portosystemic shunt
A Transjugular Intrahepatic Portosystemic Shunt is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein...

 (TIPS) is similar to a surgical shunt. It accomplishes the same goal but has a lower procedure-related mortality, which has led to a growth in its popularity. Patients with stenosis or vena caval obstruction may benefit from angioplasty
Angioplasty
Angioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size...

. Limited studies on thrombolysis
Thrombolysis
Thrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...

 with direct infusion of urokinase
Urokinase
Urokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...

 and tissue plasminogen activator
Tissue plasminogen activator
Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...

 (tPA) into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted.

Liver transplantation
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...

 is an effective treatment for Budd-Chiari. It is generally reserved for patients with fulminant hepatic 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 score
Child-Pugh score
In medicine , the Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis...

s, elevated prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...

, and altered serum levels of various substances (sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

, creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...

, albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...

, and bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

). Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, patients with myeloproliferative disorders may progress to acute leukemia independent of Budd–Chiari syndrome.
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