leads to side effects or complications, the only remaining option is liver transplantation. this is reserved for those with severe symptoms, as it carries a mortality of about 10%, but leads to good results if successful. the exact point at which liver transplantion is to be offered is not yet completely established. embolization treatment has been attempted, but leads to severe complications in a proportion of patients and is discouraged. other liver-related complications (portal hypertension, esophageal varices, ascites, hepatic encephalopathy) are treated with the same modalities as used in cirrhosis, although the use of transjugular intrahepatic portosystemic shunt treatment is discouraged due to the lack of documented benefit. brain avms the decision to treat brain arteriovenous malformations depends on the symptoms that they cause (such as seizures or headaches). the bleeding risk is predicted by previous episodes of hemorrhage, and whether on the cta or mra scan the avm appears to be deep-seated or have deep venous drainage. size of the avm and the presence of aneurysms appears to matter less. in hht, some lesions (high-flow arteriovenous fistulae) tend to cause more problems, and treatment is warranted. other avms may regress over time without intervention. various modalities are available, depending on the location of the avm and its size: surgery, radiation-based treatment and embolization. sometimes, multiple modalities are used on the same lesion. surgery (by craniotomy, open brain surgery) may be offered based on the risks of treatment as determined by the spetzler–martin scale (grade i-v); this score is higher in larger lesions that are close to important brain structures and have deep venous drainage. high grade lesions (iv and v) have an unacceptably high risk and surgery is not typically offered in those cases. radiosurgery (using targeted radiation therapy such as by a gamma knife) may be used if the lesion is small but close to vital structures. finally, embolization may be used on small lesions that have only a single feeding vessel. experimental treatments several anti-angiogenesis drugs approved for other conditions, such as cancer, have been investigated in small clinical trials. the anti-vegf antibody bevacizumab, for instance, has been used off-label in several studies. in a large clinical trial, bevacizumab infusion was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis in treated hht patients. thalidomide, another anti-angiogenesis drug, was also reported to have beneficial effects in hht patients. thalidomide treatment was found to induce vessel maturation in an experimental mouse model of hht and to reduce the severity and frequency of nosebleeds in the majority of a small group of hht patients. the blood hemoglobin levels of these treated patients rose as a result of reduced hemorrhage and enhanced blood vessel stabilization. epidemiology the netherlands antilles, where hht is more common than anywhere in the world, located off the coast of venezuela. population studies from numerous areas in the world have shown that hht occurs at roughly the same rate in almost all populations: somewhere around 1 in 5000. in some areas, it is much more common; for instance, in the french region of haut jura the rate is 1:2351 - twice as common as in other populations. this has been attributed to a founder effect, in which a population descending from a small number of ancestors has a high rate of a particular genetic trait because one of these ancestors harbored this trait. in haut jura, this has been shown to be the result of a particular acvrl1 mutation (named c.1112dupg or c.1112_1113insg). the highest rate of hht is 1:1331, reported in bonaire and curaçao, two islands in the caribbean belonging to the netherlands antilles. most people with hht have a normal lifespan. the skin lesions and nosebleeds tend to develop during childhood. avms are probably present from birth, but don't necessarily cause any symptoms. frequent nosebleeds are the most common symptom and can significantly affect quality of life. history several 19th century english physicians, starting with henry gawen sutton (1836–1891) and followed by benjamin guy babington (1794–1866) and john wickham legg (1843–1921), described the most common features of hht, particularly the recurrent nosebleeds and the hereditary nature of the disease. the french physician henri jules louis marie rendu (1844–1902) observed the skin and mucosal lesions, and distinguished the condition from hemophilia. the canadian-born sir william osler (1849–1919), then at johns hopkins hospital and later at oxford university, made further contributions with a 1901 report in which he described characteristic lesions in the digestive tract. the english physician frederick parkes weber (1863–1962) reported further on the condition in 1907 with a series of cases. the term "hereditary hemorrhagic telangiectasia" was first used by the american physician frederic m. hanes (1883–1946) in a 1909 article on the condition. the diagnosis of hht remained a clinical one until the genetic defects that cause hht were identified by a research group at duke university medical center, in 1994 and 1996 respectively. in 2000, the international scientific advisory committee of curehht formerly called the hht foundation international published the now widely used curaçao criteria. in 2006, a group of international experts met in canada and formulated an evidence-based guideline, sponsored by curehht. this guideline has since been updated in 2020 and can be found here.