Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement

Boillot, Olivier; Bianco, Francesco; Viale, Jean–Paul; Mion, François; Mechet, Isabelle; Gille, D.; Delaye, J; Paliard, P; Plauchu, Henri

doi:10.1016/s0016-5085(99)70243-x

Cited by 77 publications

(70 citation statements)

References 21 publications

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“…2 The spectrum of disease within the HHT umbrella has extended beyond the telangiectatic/AVM HHT pathology delineated by the Curaçao criteria. 2 More recently recognised features include pulmonary arterial hypertension 10 ; juvenile polyposis 11 ; pulmonary hypertension in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [12][13][14][15][16] ; a prothrombotic state associated with elevated plasma levels of factor VIII 17 , and potential immune dysfunction. 18 Three of the genes mutated in HHT have been identified: endoglin (resulting in HHT1, OMIM #187300) 19 ; ACRVL1/ALK1; (resulting in HHT2, OMIM#600376) 20 , and more rarely, SMAD4 (mutated in HHT in association with juvenile polyposis, JPHT OMIM #175050) 11 .…”

Section: Overview Of Hhtmentioning

confidence: 99%

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Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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Hereditary haemorrhagic telangiectasia, inherited as an autosomal dominant trait, affects approximately 1 in 5,000 people. The abnormal vascular structures in HHT result from mutations in genes (most commonly endoglin or ACVRL1) whose protein products influence TGF-ß superfamily signalling in vascular endothelial cells. The cellular mechanisms underlying the generation of HHT telangiectasia and arteriovenous malformations are being unravelled, with recent data focussing on a defective response to angiogenic stimuli in particular settings. For affected individuals, there is often substantial morbidity due to sustained and repeated haemorrhages from telangiectasia in the nose and gut. Particular haematological clinical challenges include the management of severe iron deficiency anaemia; handling the intricate balance of antiplatelet or anticoagulants for HHT patients in whom there are often compelling clinical reasons to use such agents; and evaluation of apparently attractive experimental therapies promoted in high profile publications when guidelines and reviews are quickly superseded. There is also a need for sound screening programmes for silent arteriovenous malformations. These occur commonly in the pulmonary, cerebral, and hepatic circulations, may haemorrhage, but predominantly result in more complex pathophysiology due to consequences of defective endothelium, or shunts that bypass specific capillary beds. This review will focus on the new evidence and concepts in this complex and fascinating condition, placing these in context for both clinicians and scientists, with a particular emphasis on haematological settings. Blood Reviews _ HHT 2010_ Shovlin 3 Overview of HHTHHT, also known as Osler Weber Rendu syndrome [1][2][3] , is one of the most common disorders to be inherited as an autosomal dominant trait. Careful epidemiological studies reveal that it affects approximately 1 in 5,000 individuals, 4,5 with regional differences, 6 and isolated communities displaying higher prevalences due to founder effects. 7 8 HHT was first described as a familial disease characterised by severe recurrent nasal and gastrointestinal bleeding with associated anaemia, and visible dilated blood vessels (telangiectasia) on the lips and finger tips. The majority of HHT patients are also affected by larger arteriovenous malformations (AVMs) in the pulmonary, hepatic, cerebral, pancreatic, spinal and other circulations. 1,2,9 These features, presented in more detail within Table 1, are used as criteria to diagnose HHT. 2 The spectrum of disease within the HHT umbrella has extended beyond the telangiectatic/AVM HHT pathology delineated by the Curaçao criteria. 2 More recently recognised features include pulmonary arterial hypertension 10 ; juvenile polyposis 11 ; pulmonary hypertension in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [12][13][14][15][16] ; a prothrombotic state associated with elevated plasma levels of factor VIII 17 , and poten...

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Section: Overview Of Hhtmentioning

confidence: 99%

“…HHT2 patients are also at higher risk of post capillary pulmonary hypertension associated with hepatic AVMs. [12][13][14][15][16] Blood Reviews _ HHT 2010_ Shovlin 11 …”

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confidence: 99%

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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“…Interestingly, the diameter of the hepatic artery has previously been shown to be the most specific criteria for liver involvement in HHT patients with advanced liver disease, without overlapping values compared with different control groups. 10 Confirming these data by direct intracardiac measurement of cardiac output, as is our general rule before liver transplantation, 20 would be of considerable interest.…”

Section: Discussionmentioning

confidence: 84%

“…10 The question remains as to whether higher cardiac output, as estimated from echocardiography, will be associated on a long-term basis with a higher risk of cardiac failure: clarifying this point is a major objective for the long-term follow-up of the current cohort of patients; however, previous series have clearly shown very high values for the cardiac index in HHT patients with severe liver involvement and complete resolution after liver transplantation. 19,20 We are now following these patients at 1-year to 3-year intervals, which appears to be the only way to determine whether a high cardiac index is responsible for negative cardiac evolution, and we also now use the B-type natriuretic factor to monitor patients with a high cardiac index (not shown). Interestingly, in this series, the three patients considered for liver transplantation because of major bleeding and a modified general state of health, associated with advanced hepatic fistulas, had a relatively high cardiac index (3.4, 3.6, and 6.6 L/min/m 2 , respectively).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

Gincul¹,

Lesca²,

Gelas-Dore³

et al. 2008

Hepatology

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H ereditary hemorragic telangiectasia (HHT) is an autosomal dominant genetic disease driven by mutations in genes such as endoglin (ENG), activin receptor-like kinase type 1 (ACVRL1), and Smad-4, which control the transforming growth factor beta proliferation pathway. 1 HHT patients usually develop a wide range of cutaneous, mucosal, and sometimes visceral arteriovenous malformations. [2][3][4] The symptomatology is dominated by epistaxis and anemia, but potentially life-threatening visceral localizations can be present, such as pulmonary, hepatic, and cerebral vascular malformations. 5 Hepatic involvement in HHT has been described in several studies. 6,7 Characteristic HHT hepatic localization consists of arteriovenous shunting responsible, in severe cases, for high-output cardiac failure (fistulas between the hepatic artery and hepatic veins), ascites (fistulas between the hepatic artery and portal veins), and cholangiopathy with sepsis. Liver transplantation is the main treatment option at these advanced stages. Previous, mostly small series have shown Doppler sonography (DS) abnormalities in 30% to 70% of HHT patients. 8,9 Early and advanced DS findings include (1) enlargement, increased flow velocity, and tortuosity of hepatic artery branches; (2) increased diameter and flow velocity in he-

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“…Vaso-occlusion of pulmonary AVMs in this context may unmask moderate pulmonary hypertension [6] and, conversely, may contribute to a decrease in cardiac output [7]. Management of HHT patients with high-output cardiac failure is difficult; correction of anaemia, liver transplantation [8], banding of the hepatic artery [9], bevacizumab [10] and, possibly, arterial embolisation of liver AVMs (but with a significant risk of complications) may be considered. No recommendation is available regarding the management of pulmonary AVMs in patients with increased cardiac output.…”

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Near-fatal haemorrhage from pulmonary arteriovenous malformation in HHT with increased cardiac output: FIGURE 1.

Cottin¹,

Gamondès²,

Schüller³

et al. 2009

Eur Respir Rev

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We read with interest the report by MONTANI et al.[1] of fatal rupture of pulmonary arteriovenous malformation (AVM) in a patient with hereditary haemorrhagic telangiectasis (HHT) and severe pulmonary arterial hypertension (PAH) confirmed by right heart catheterisation. The authors hypothesised that bleeding from pulmonary AVM may have been facilitated by increased mean pulmonary artery pressure (Ppa). Here, we report a patient with near-fatal haemorrhage from pulmonary AVM, probably facilitated by increased cardiac output, but without severe PAH.A 35-yr-old female nonsmoker, with a history of obesity and fenfluramide use 10 yrs previously for 2 months, was admitted for exertional dyspnoea during pregnancy. Arterial blood gases showed arterial oxygen tension (Pa,O 2 ) of 8.2 kPa, and arterial carbon dioxide tension of 3.5 kPa, with markedly increased alveolar-arterial oxygen tension difference on 100% oxygen (74 kPa, normally ,18.6 kPa). Chest radiograph revealed numerous pulmonary AVMs. Transthoracic contrast echocardiography showed estimated systolic Ppa of 47 mmHg with moderate dilatation of the right heart cavities, and extracardiac right-to-left shunting. She had recurrent epistaxis since childhood, numerous characteristic telangiectasiae, and possible familial HHT in her paternal grandmother. HHT was diagnosed according to the Curaçao criteria [2]. One deletion was found in exon 9 of the ENG gene, and analysis of the ACVRL1 gene was normal. Long-term oxygen therapy was initiated. Emergency caesarean delivery was performed at 25 weeks of gestation because of a fetal growth defect.

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Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement

Cited by 77 publications

References 21 publications

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

Near-fatal haemorrhage from pulmonary arteriovenous malformation in HHT with increased cardiac output: FIGURE 1.

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