• Hereditary hemorrhagic telangiectasia
• Pulmonary arteriovenous malformations
• Pulmonary circulation
• Pulmonary right-to-left shunt
• Transthoracic contrast echocardiography

• Humans
• Telangiectasia, Hereditary Hemorrhagic/complications
• Telangiectasia, Hereditary Hemorrhagic/diagnostic imaging
• Female
• Male
• Middle Aged
• Prospective Studies
• Pulmonary Veins/abnormalities
• Pulmonary Veins/diagnostic imaging
• Follow-Up Studies
• Adult
• Aged
• Pulmonary Artery/abnormalities
• Pulmonary Artery/diagnostic imaging
• Echocardiography
• Arteriovenous Fistula/diagnostic imaging
• Arteriovenous Fistula/complications
• Arteriovenous Malformations/diagnostic imaging
• Arteriovenous Malformations/complications
• Disease Progression

• Hepatic encephalopathy
• Hereditary hemorrhagic telangiectasia
• Portosystemic malformations
• Rare diseases

• Humans
• Male
• Female
• Telangiectasia, Hereditary Hemorrhagic/complications
• Telangiectasia, Hereditary Hemorrhagic/physiopathology
• Cross-Sectional Studies
• Middle Aged
• Adult
• Hepatic Encephalopathy
• Aged
• Vascular Malformations/physiopathology
• Neuropsychological Tests
• Quality of Life

• PI20/00592 Instituto de Salud Carlos III
• PI23/00164 Instituto de Salud Carlos III

• clinical significance
• hereditary hemorrhagic telangiectasia diagnosis
• plasmatic angiogenic biomarkers

• bevacizumab
• hereditary haemorrhagic telangiectasia
• pulmonary arterial hypertension
• pulmonary vascular disease

• Humans
• Telangiectasia, Hereditary Hemorrhagic/complications
• Telangiectasia, Hereditary Hemorrhagic/therapy
• Female
• Middle Aged
• Adult
• von Willebrand Diseases/complications
• von Willebrand Diseases/epidemiology
• Epistaxis/etiology
• Anemia, Iron-Deficiency/etiology
• Aged
• Cohort Studies

• K23 HL159313 NHLBI NIH HHS

• disease impact
• epistaxis
• fatigue
• hereditary hemorrhagic telangiectasia
• patient-reported outcome measures
• quality of life
• quality of life metrics
• self-perceived health
• symptom burden
• vascular malformations

• Humans
• Epistaxis/therapy
• Quality of Life
• Prospective Studies
• Cross-Sectional Studies
• Telangiectasia, Hereditary Hemorrhagic/epidemiology
• Telangiectasia, Hereditary Hemorrhagic/therapy
• Telangiectasia, Hereditary Hemorrhagic/complications
• Case-Control Studies
• Retrospective Studies
• Outcome Assessment, Health Care
• Gastrointestinal Hemorrhage/complications
• Randomized Controlled Trials as Topic

• Activin
• Androgen
• BMP
• BMPR2
• Endothelial
• HHT
• Hypertension
• Oestrogen
• PAH
• TGFβ

• Female
• Male
• Humans
• Pulmonary Arterial Hypertension
• Transforming Growth Factor beta/metabolism
• Familial Primary Pulmonary Hypertension
• Hypertension, Pulmonary
• Signal Transduction
• Bone Morphogenetic Protein Receptors, Type II/genetics
• Bone Morphogenetic Protein Receptors, Type II/metabolism

• Netherlands Cardiovascular Research Initiative
• Dutch Heart Foundation
• Dutch Federation of University Medical Centres
• Netherlands Organization for Health Research and Development
• Royal Netherlands Academy of Sciences
• Fundacio La Marato de TV3
• Spanish Ministry of Science
• Ramón y Cajal
• PROMETHEUS

• Cardiovascular Abnormalities
• Liver Diseases
• Phenotype

• Male
• Humans
• Female
• Telangiectasia, Hereditary Hemorrhagic/complications
• Telangiectasia, Hereditary Hemorrhagic/diagnosis
• Telangiectasia, Hereditary Hemorrhagic/genetics
• Epistaxis/complications
• Liver
• Intracranial Arteriovenous Malformations
• Mutation

Hereditary hemorrhagic teleangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is the most common cause of hepatic vascular malformations in adults. Different vascular shunts (arteriovenous, arterioportal or portovenous) lead to different clinical manifestations. Even though no hepatic-related symptoms are reported in the majority of cases, the severity of liver disease could lead to refractory medical conditions, in some cases requiring liver transplantation. The aim of this manuscript is to provide an updated overview of the current evidence regarding the diagnosis and treatment of HHT liver involvement and liver-related complications.

• Hereditary hemorrhagic teleangiectasia
• Rendu-Osler-Weber syndrome
• Hepatic vascular malformations
• Liver

• RNA
• genetic testing
• hereditary hemorrhagic telangiectasia
• splicing
• variant of unknown significance

• PI20/00592 Instituto de Salud Carlos III
• FI21/00007 Instituto de Salud Carlos III

• Gender
• Portal hypertension
• Pregnancy
• Sex

• Pregnancy
• Humans
• Female
• Liver Diseases/therapy
• Liver/blood supply
• Telangiectasia, Hereditary Hemorrhagic
• Budd-Chiari Syndrome/therapy
• Venous Thrombosis
• Portal Vein

Osler Weber Rendu Syndrome (OWS) is characterized by the development of abnormally dilated blood vessels, which manifest as arteriovenous shunts (pulmonary, gastrointestinal, hepatic, and cerebral) and mucocutaneous telangiectasias (lips, tongue, and fingertips). It is an autosomal dominant disease with a defect in transforming growth factor beta superfamily genes. This defect results in increased angiogenesis and disruption of vessel wall integrity. The disease remains underreported, with occasional history of recurrent epistaxis, iron deficiency anemia, and gastrointestinal bleeding in moderate to severe cases. Diagnosis is based on clinical presentation and confirmed by genetic testing. Various local (nasal saline, air humidification, laser ablation, and electric cauterization for epistaxis and endoscopic Argon Plasma Coagulation-APC for active GI bleeding), surgical, and systemic (tranexamic acid and antiangiogenic agents like bevacizumab and thalidomide) treatment options are used depending upon disease severity. Here, we present a case with recurrent gastrointestinal bleeding refractory to endoscopic APC ablation and thalidomide and severe symptomatic anemia requiring multiple packed red cell transfusions. The patient was ultimately started on bevacizumab, to which he had a good response and has remained in remission for 8 months as of now. This case emphasizes the need to have a low threshold of suspicion to diagnose HHT and start targeted therapy like bevacizumab early on in moderate to severe cases of HHT rather than just relying on temporizing palliative measures like ablation, cauterization, and tranexamic acid.

• Osler Weber Rendu Syndrome
• bevacizumab
• case report
• diagnosis
• gastrointestinal bleeding
• hereditary hemorrhagic telangiectasia
• management
• refractory anemia

The aim was to describe three patients with hemorrhagic hereditary telangiectasia (HHT) requiring liver transplantation (LT) and to perform a systematic review focusing on surgical complications and long-term follow-up. Unrestricted searches of the Medline and Embase databases were performed through February 2022. Forty-five studies were selected including 80 patients plus the three new reported patients, 68 (81.9%) were female and mean age was 50 (27–72) years. Main indications for LT were high-output cardiac failure (n = 40; 48.2%), ischemic cholangitis (n = 19; 22.9%), and a combination of both conditions (n = 13;15.6%). Mean cold ischemic time and red blood cell units transfused during LT were 554 (300–941) minutes and 11.4 (0–88) units, respectively. Complications within 30 days were described in 28 (33.7%) patients, mainly bleeding complications in 13 patients, hepatic artery (HA) thrombosis in four and hepatic vein thrombosis in one. Mean follow-up was 76.4 (1–288) months, and during it, four new patients developed thrombotic complications in HA, HA aneurysm, celiac artery, and the portal–splenic–mesenteric vein. HHT relapse in the transplant allograft was detected in 13 (17.1%) patients after 1–19 years (including two fatal recurrences). Overall mortality was 12%. In conclusion, previous assessment of HA anatomy and hyperdynamic circulatory state could reduce LT complications. The risk of relapse in the hepatic graft supports a multidisciplinary follow-up for HHT patients with LT.

Appropriate management of hereditary hemorrhagic telangiectasia (HHT) is of particular importance in females, as HHT-mediated modifications of the vascular bed and circulation are known to increase the risk of complications during pregnancy and delivery. This study was undertaken to evaluate female HHT patients’ awareness of and experience with HHT during pregnancy and delivery, with a focus on epistaxis. In this retrospective study, 46 females (median age: 60 years) with confirmed HHT completed a 17-item questionnaire assessing knowledge of HHT and its pregnancy-associated complications, the severity of epistaxis during past pregnancies and deliveries, and the desire for better education and counselling regarding HHT and pregnancy. Results revealed that 85% of participants were unaware of their disease status prior to the completion of all pregnancies. Further, 91% reported no knowledge of increased pregnancy-related risk due to HHT. In regard to epistaxis, 61% of respondents reported experiencing nosebleeds during pregnancy. Finally, approximately a third of respondents suggested that receiving counseling on the risks of HHT in pregnancy could have been helpful. Findings suggest that awareness of HHT and its potential for increasing pregnancy-related risk is poor. Best practices in HHT management should be followed to minimize negative effects of the disorder.

• Morbus Osler
• Osler Calendar
• Rendu–Osler–Weber syndrome
• arteriovenous malformations
• epistaxis
• hereditary hemorrhagic telangiectasia
• laser therapy
• orphan disease
• pregnancy

• ALK1
• BMP9
• endoglin
• growth factors
• hereditary haemorrhagic telangiectasia
• maturation

• Nd:YAG laser
• dual PDL-Nd:YAG laser
• hereditary hemorrhagic telangiectasia
• pulsed dye laser

• emergency medicine
• respiratory medicine

• antiangiogenic properties
• epistaxis
• epistaxis severity score
• hereditary hemorrhagic telangiectasia
• nasal endoscopy
• propranolol gel

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by multiple telangiectases and caused by germline disease-causing variants in the ENG (HHT1), ACVRL1 (HHT2) and, to a lesser extent MADH4 and GDF2, which encode proteins involved in the TGF-β/BMP9 signaling pathway. Common visceral complications of HHT are caused by pulmonary, cerebral, or hepatic arteriovenous malformations (HAVMs). There is large intrafamilial variability in the severity of visceral involvement, suggesting a role for modifier genes. The objective of the present study was to investigate the potential role of ENG, ACVRL1, and of other candidate genes belonging to the same biological pathway in the development of HAVMs.

We selected 354 patients from the French HHT patient database who had one disease causing variant in either ENG or ACVRL1 and who underwent hepatic exploration. We first compared the distribution of the different types of variants with the occurrence of HAVMs. Then, we genotyped 51 Tag-SNPs from the Hap Map database located in 8 genes that encode proteins belonging to the TGF-β/BMP9 pathway (ACVRL1, ENG, GDF2, MADH4, SMAD1, SMAD5, TGFB1, TGFBR1), as well as in two additional candidate genes (PTPN14 and ADAM17). We addressed the question of a possible genetic association with the occurrence of HAVMs.

The proportion of patients with germline ACVRL1 variants and the proportion of women were significantly higher in HHT patients with HAVMs. In the HHT2 group, HAVMs were more frequent in patients with truncating variants. Six SNPs (3 in ACVRL1, 1 in ENG, 1 in SMAD5, and 1 in ADAM17) were significantly associated with HAVMs. After correction for multiple testing, only one remained significantly associated (rs2277383).

In this large association study, we confirmed the strong relationship between ACVRL1 and the development of HAVMs. Common polymorphisms of ACVRL1 may also play a role in the development of HAVMs, as a modifying factor, independently of the disease-causing variants.

• ACVRL1
• HHT, Rendu-Osler
• Hepatic arteriovenous malformation
• Modifier gene

• ACVRL1 protein, human
• Anemia
• Antifibrinolytic agents
• Endoglin
• Epistaxis, Osler-Rendu-weber disease
• Iron
• Telangiectasia, hereditary hemorrhagic

• Activin Receptors, Type II
• Epistaxis/etiology
• Epistaxis/genetics
• Genotype
• Humans
• Phenotype
• Retrospective Studies
• Telangiectasia, Hereditary Hemorrhagic/drug therapy
• Telangiectasia, Hereditary Hemorrhagic/genetics

• T32 HL007149 NHLBI NIH HHS