Hepatic veno-occlusive disease
Encyclopedia
Hepatic veno-occlusive disease or veno-occlusive disease (VOD) is a condition in which some of the small veins in the liver
are blocked. It is a complication
of high-dose chemotherapy
given before a bone marrow transplant
(BMT) and is marked by weight gain due to fluid retention
, increased liver size
, and raised levels of bilirubin
in the blood. The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation.
Apart from chemotherapy, VOD may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas), and has been described as part of a rare hereditary disease called hepatic venoocclusive disease with immunodeficiency (which results from mutations in the gene coding for a protein called SP110
).
, ascites
, and increased bilirubin
. It often is associated with renal failure
.
is required for a definitive diagnosis.
Toxic agents causing veno-occlusive disease include plants as well as the medication cyclophosphamide.
is an investigational treatment that may be promising. Defibrotide is a polydeoxyribonucleotide isolated from pig intestine. Although its mechanism of action in VOD is unclear, the drug is believed to have antithrombotic properties. In August 2009, Gentium S.p.A., which sponsored the phase 3 clinical trial (pivotal) of defibrotide in hepatic VOD, announced disappointing results. Further clinical development of defibrotide for this indication is uncertain.
poisoning in South Africa
. Subsequent reports were mostly in Jamaicans who had consumed herbal teas. With the advent of bone marrow transplanation, most later reported cases have been in those undergoing treatment for leukemia.
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...
are blocked. It is a complication
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
of high-dose chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
given before a 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...
(BMT) and is marked by weight gain due to fluid retention
Water retention (medicine)
The term water retention signifies an abnormal accumulation of fluid in the circulatory system or within the tissues or cavities of the body.Water is found both inside and outside the body’s cells...
, increased liver size
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...
, and raised levels of 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...
in the blood. The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation.
Apart from chemotherapy, VOD may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas), and has been described as part of a rare hereditary disease called hepatic venoocclusive disease with immunodeficiency (which results from mutations in the gene coding for a protein called SP110
SP110
Sp110 nuclear body protein is a protein that in humans is encoded by the SP110 gene.-External links:*-Further reading:...
).
Signs and symptoms
Features of VOD include weight gain, tender hepatomegalyHepatomegaly
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...
, 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 increased 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...
. It often is associated with renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
Diagnosis
Hepatic doppler ultrasound is typically utilized to confirm or suggest the diagnosis. Most common findings on liver doppler ultrasound include increased phasicity of portal veins with eventual development of portal flow reversal. The liver is usually enlarged but maintained normal echogenicity. A liver biopsyLiver 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 required for a definitive diagnosis.
Pathophysiology
In the BMT setting, VOD is felt to be due to injury to the hepatic venous endothelium from the conditioning regimen.Toxic agents causing veno-occlusive disease include plants as well as the medication cyclophosphamide.
Treatment
Treatment for VOD is primarily supportive. In the BMT setting, defibrotideDefibrotide
Defibrotide is a deoxyribonucleic acid derivative derived from cow lung or porcine mucosa. It is an anticoagulant with a multiple mode of action .It has been used with antithrombin III.-Pharmacokinetics:...
is an investigational treatment that may be promising. Defibrotide is a polydeoxyribonucleotide isolated from pig intestine. Although its mechanism of action in VOD is unclear, the drug is believed to have antithrombotic properties. In August 2009, Gentium S.p.A., which sponsored the phase 3 clinical trial (pivotal) of defibrotide in hepatic VOD, announced disappointing results. Further clinical development of defibrotide for this indication is uncertain.
Prognosis
When associated with bone marrow transplant, VOD is fatal in over 30% of cases. Cases due to plant alkaloids often have a longer and more unpredictable course.History
The first report on veno-occlusive disease, in 1920, was as a result senecioSenecio
Senecio is a genus of the daisy family that includes ragworts and groundsels. The flower heads are normally rayed, completely yellow, and the heads are borne in branched clusters...
poisoning in South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
. Subsequent reports were mostly in Jamaicans who had consumed herbal teas. With the advent of bone marrow transplanation, most later reported cases have been in those undergoing treatment for leukemia.