Hepatic veno-occlusive disease | |
---|---|
Other names | Veno-occlusive disease with immunodeficiency Sinusoidal obstruction syndrome |
Specialty | Gastroenterology ![]() |
Symptoms | Weight gain, tender enlargement of the liver, ascites, jaundice |
Diagnostic method | Liver biopsy |
Differential diagnosis | Budd–Chiari syndrome |
Prevention | Ursodeoxycholic acid |
Treatment | Defibrotide |
Deaths | 10-20% |
Hepatic veno-occlusive disease (VOD) or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given before a bone marrow transplant and/or excessive exposure to hepatotoxic pyrrolizidine alkaloids. It is classically marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood. [1] The name sinusoidal obstruction syndrome (SOS) is preferred if hepatic veno-occlusive disease happens as a result of chemotherapy or bone marrow transplantation. [1] [2]
Apart from chemotherapy, hepatic veno-occlusive disease may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas), [1] 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). [3]
Features of hepatic veno-occlusive disease include weight gain, tender enlargement of the liver, ascites, and yellow discoloration of the skin; it often is associated with acute kidney failure. [4]
In the bone marrow transplant setting, hepatic veno-occlusive disease 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.[ citation needed ]
Doppler ultrasound of the liver is typically utilized to confirm or suggest the diagnosis. 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 biopsy is required for a definitive diagnosis.[ citation needed ]
Treatment generally includes supportive care including pain management and possibly diuretics. [5] In those with severe disease due to a bone marrow transplant, defibrotide is a proposed treatment. [6] It has been approved for use in severe cases in Europe and the United States. [7] [8] A placebo controlled trial, however, has not been done as of 2016. [5]
Mild disease has a risk of death of about 10% while moderate disease has a risk of death of 20%. [5] When it occurs as a result of bone marrow transplant and multiorgan failure is present, the risk of death is greater than 80%. [6]
The first report on veno-occlusive disease, in 1920, was as a result of senecio poisoning in South Africa. [9] Subsequent reports were mostly in Jamaicans who had consumed herbal teas. [1] With the advent of bone marrow transplantation, most cases since its introduction have been in those undergoing treatment for leukemia. [1]
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.
Tussilago farfara, commonly known as coltsfoot, is a plant in the tribe Senecioneae in the family Asteraceae, native to Europe and parts of western and central Asia. The name "tussilago" is derived from the Latin tussis, meaning cough, and ago, meaning to cast or to act on. It has had uses in traditional medicine, but the discovery of toxic pyrrolizidine alkaloids in the plant has resulted in liver health concerns.
Busulfan is a chemotherapy drug in use since 1959. It is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Its chemical designation is 1,4-butanediol dimethanesulfonate.
Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.
Defibrotide, sold under the brand name Defitelio, is a mixture of single-stranded oligonucleotides that is purified from the intestinal mucosa of pigs. It is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant, with different limitations in the US and the European Union. It works by protecting the cells lining blood vessels in the liver and preventing blood clotting; the way it does this is not well understood.
Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect herbivores. More than 660 PAs and PA N-oxides have been identified in over 6,000 plants, and about half of them exhibit hepatotoxicity. They are found frequently in plants in the Boraginaceae, Asteraceae, Orchidaceae and Fabaceae families; less frequently in the Convolvulaceae and Poaceae, and in at least one species in the Lamiaceae. It has been estimated that 3% of the world’s flowering plants contain pyrrolizidine alkaloids. Honey can contain pyrrolizidine alkaloids, as can grains, milk, offal and eggs. To date (2011), there is no international regulation of PAs in food, unlike those for herbs and medicines.
Peliosis hepatis is an uncommon vascular condition characterised by multiple, randomly distributed, blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimetres and 3 cm in diameter. In the past, it was a mere histological curiosity occasionally found at autopsies, but has been increasingly recognised with wide-ranging conditions from AIDS to the use of anabolic steroids. It also occasionally affects spleen, lymph nodes, lungs, kidneys, adrenal glands, bone marrow, and other parts of gastrointestinal tract.
Hepatosplenic T-cell lymphoma is a rare form of lymphoma that is generally incurable, except in the case of an allogeneic stem cell transplant. It is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show significant sinusoidal infiltration in the liver, spleen, and bone marrow.
The liver is a major metabolic organ only found in vertebrate animals, which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm and mostly shielded by the lower right rib cage. Its other metabolic roles include carbohydrate metabolism, the production of hormones, conversion and storage of nutrients such as glucose and glycogen, and the decomposition of red blood cells.
Transplantable organs and tissues may refer to both organs and tissues that are relatively often transplanted, as well as organs and tissues which are relatively seldom transplanted. In addition to this it may also refer to possible-transplants which are still in the experimental stage.
Senecionine is a toxic pyrrolizidine alkaloid isolated from various botanical sources. It takes its name from the Senecio genus and is produced by many different plants in that genus, including Jacobaea vulgaris. It has also been isolated from several other plants, including Brachyglottis repanda, Emilia, Erechtites hieraciifolius, Petasites, Syneilesis, Crotalaria, Caltha leptosepala, and Castilleja.
Pyrrolizidine alkaloidosis is a disease caused by chronic poisoning found in humans and other animals caused by ingesting poisonous plants which contain the natural chemical compounds known as pyrrolizidine alkaloids. Pyrrolizidine alkaloidosis can result in damage to the liver, kidneys, heart, brain, smooth muscles, lungs, DNA, lesions all over the body, and could be a potential cause of cancer. Pyrrolizidine alkaloidosis is known by many other names such as "Pictou Disease" in Canada and "Winton Disease" in New Zealand. Cereal crops and forage crops can sometimes become polluted with pyrrolizidine-containing seeds, resulting in the alkaloids contaminating flour and other foods, including milk from cows feeding on these plants.
Riddelliine is a chemical compound classified as a pyrrolizidine alkaloid. It was first isolated from Senecio riddellii and is also found in a variety of plants including Jacobaea vulgaris, Senecio vulgaris, and others plants in the genus Senecio.
Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in immunodeficiency. Individuals with RD have mutations in both copies of the AK2 gene. Mutations in this gene lead to absence of AK2 protein. AK2 protein allows hematopoietic stem cells to differentiate and proliferate. Hematopoietic stem cells give rise to blood cells.
The haematopoietic system is the system in the body involved in the creation of the cells of blood.
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension caused by progressive blockage of the small veins in the lungs. The blockage leads to high blood pressures in the arteries of the lungs, which, in turn, leads to heart failure. The disease is progressive and fatal, with median survival of about 2 years from the time of diagnosis to death. The definitive therapy is lung transplantation.
Liver sinusoidal endothelial cells (LSECs) form the lining of the smallest blood vessels in the liver, also called the hepatic sinusoids. LSECs are highly specialized endothelial cells with characteristic morphology and function. They constitute an important part of the reticuloendothelial system (RES).
Echites umbellatus is a flowering climber, belonging to subfamily Apocynoideae of the family Apocynaceae and has the English common name devil's potato. It was first described in 1760 by Dutch botanist, Nikolaus Joseph von Jacquin. The species grows in parts of Florida, Tabasco, Yucatán Peninsula, Belize, Honduras, Cayman Islands, Cuba, Hispaniola, Jamaica, Leeward Islands, Bahamas, Turks and Caicos Islands, and the Colombian islands in the Western Caribbean.