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Ielasi L, Tonnini M, Piscaglia F, Serio I. Current guidelines for diagnosis and management of hepatic involvement in hereditary hemorrhagic teleangiectasia. World J Hepatol 2023; 15:675-687. [PMID: 37305373 PMCID: PMC10251273 DOI: 10.4254/wjh.v15.i5.675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/04/2023] [Accepted: 04/12/2023] [Indexed: 05/24/2023] Open
Abstract
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.
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Affiliation(s)
- Luca Ielasi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza 48018, Italy
| | - Matteo Tonnini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Ilaria Serio
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
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Perioperative Complications and Long-Term Follow-Up of Liver Transplantation in Hemorrhagic Hereditary Telangiectasia: Report of Three Cases and Systematic Review. J Clin Med 2022; 11:jcm11195624. [PMID: 36233492 PMCID: PMC9573297 DOI: 10.3390/jcm11195624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/11/2022] [Accepted: 09/19/2022] [Indexed: 11/17/2022] Open
Abstract
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.
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Dumortier J, Dupuis-Girod S, Valette PJ, Valent A, Guillaud O, Saurin JC, Hervieu V, Robinson P, Plauchu H, Paliard P, Boillot O, Scoazec JY. Recurrence of Hereditary Hemorrhagic Telangiectasia After Liver Transplantation: Clinical Implications and Physiopathological Insights. Hepatology 2019; 69:2232-2240. [PMID: 30549294 DOI: 10.1002/hep.30424] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/03/2018] [Indexed: 02/04/2023]
Abstract
Liver transplantation (LT) has been proposed as a curative treatment in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement. We provide a long-term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence. The present study included all patients prospectively followed up after LT for HHT in the Lyon Liver Transplant Unit from 1993 to 2010, with a survival of more than 1 year. Protocol clinical, radiological, and histological examinations were performed at regular intervals. Fourteen patients were included (13 women and one man). Median age at LT was 52.5 years (range: 33.1-66.7). In eight patients (seven female), disease recurrence was diagnosed by abnormal radiological features, suggestive of microcirculatory disturbances. Typical vascular lesions, including telangiectasia, were demonstrated by liver biopsy in five of these patients. The median interval between LT and diagnosis of recurrence was 127 months (range: 74-184). The risk of recurrence increased over time; estimated cumulative risk was 47.9% at 15 years. Liver tissue analysis found the coexistence of an angiogenic process combined with endothelial microchimerism, as shown by the presence of vascular lining cells of recipient origin. Conclusion: The present data show that disease recurrence occurs, usually after a long delay, in a significant number of patients treated by LT for liver complications of HHT. This strongly supports the necessity of a lifelong follow-up and suggests that therapeutic strategy needs discussion and evaluation, especially of the role of potential adjuvant treatments to LT, such as antiangiogenic medications, when recurrent disease appears.
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Affiliation(s)
- Jérôme Dumortier
- Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
| | - Sophie Dupuis-Girod
- Service de Génétique and Centre de Référence Pour la Maladie de Rendu-Osler, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Bron, France
| | - Pierre-Jean Valette
- Service de Radiologie Digestive, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
| | - Alexander Valent
- Département de Biologie et Pathologie Médicales, Service de Pathologie Moléculaire, Gustave Roussy Cancer Campus, Villejuif, France
| | - Olivier Guillaud
- Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
| | - Jean-Christophe Saurin
- Service d'Hépato-gastroentérologie, Hospices Civils de Lyon, Hôpital Edouard Herriot, and Université Claude Bernard Lyon 1, Lyon, France
| | - Valérie Hervieu
- Service Central d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
| | - Philip Robinson
- Direction de la Recherche Clinique et de l'Innovation, Hospices Civils de Lyon, Lyon, France
| | - Henri Plauchu
- Service de Génétique and Centre de Référence Pour la Maladie de Rendu-Osler, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Bron, France
| | - Pierre Paliard
- Service d'Hépato-gastroentérologie, Hospices Civils de Lyon, Hôpital Edouard Herriot, and Université Claude Bernard Lyon 1, Lyon, France
| | - Olivier Boillot
- Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
| | - Jean-Yves Scoazec
- Département de Biologie et Pathologie Médicales, Service de Pathologie Moléculaire, Gustave Roussy Cancer Campus, Villejuif, France.,Service Central d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, Hospices Civils de Lyon, and Université Claude Bernard Lyon 1, Lyon, France
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Medical management of haemorrhagic hereditary telangiectasia in adult patients. Med Clin (Barc) 2018; 152:274-280. [PMID: 30502301 DOI: 10.1016/j.medcli.2018.09.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 09/26/2018] [Accepted: 09/27/2018] [Indexed: 12/26/2022]
Abstract
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited Rare Disease that causes a systemic anomalous vascular overgrowth. The approach and follow-up of these patients should be from multidisciplinary units. Its diagnosis is carried out according to Curaçao clinical Criteria. Telangiectasia in the nasal mucosa cause recurrent epistaxis, the main symptom of HHT and difficult to control. The three types of hepatic shunting, hepatic artery to hepatic vein, hepatic artery to portal vein or to portal vein to hepatic vein, can cause high-output heart failure, portal hypertension or porto-systemic encephalopathy, respectively. These types of vascular involvement can be established using computerised tomography. Pulmonary arteriovenous fistula should be screened for all HHT patients by contrast echocardiography. The main objective is to review the management of epistaxis, liver and lung involvement of the adult patient with HHT.
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Hereditary Hemorrhagic Telangiectasia: Time Not Only to Recognize the Disease but Also to Prioritize the Symptomatic Patient on the Waiting List. Transplantation 2018; 103:1302-1303. [PMID: 30335700 DOI: 10.1097/tp.0000000000002492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Verhelst X, Geerts A, Van Vlierberghe H, Smeets P, Lecluyse C. Severe Hepatic and Pulmonary Involvement in Rendu-Osler-Weber Syndrome. Case Rep Gastroenterol 2018. [PMID: 29515340 PMCID: PMC5836288 DOI: 10.1159/000486189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
We report the case of a young woman with hereditary hemorrhagic telangiectasia (HHT) with severe liver involvement and pulmonary shunting. The medical imaging in this patient illustrates the severe shunting that can occur in these patients who often are asymptomatic. By showing this case, we want to highlight the role of liver transplantation in HHT with hepatic involvement.
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Affiliation(s)
- Xavier Verhelst
- aDepartment of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- aDepartment of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- aDepartment of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Peter Smeets
- bDepartment of Radiology, Ghent University Hospital, Ghent, Belgium
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Martín-Llahí M, Albillos A, Bañares R, Berzigotti A, García-Criado MÁ, Genescà J, Hernández-Gea V, Llop-Herrera E, Masnou-Ridaura H, Mateo J, Navascués CA, Puente Á, Romero-Gutiérrez M, Simón-Talero M, Téllez L, Turon F, Villanueva C, Zarrabeitia R, García-Pagán JC. Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 40:538-580. [PMID: 28610817 DOI: 10.1016/j.gastrohep.2017.03.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 03/29/2017] [Indexed: 12/11/2022]
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Ulus S, Arslan A, Karaarslan E, Cakaloglu Y. De Novo Vascular Lesions After Liver Transplant in a Case With Hereditary Hemorrhagic Telangiectasia and Fibropolycystic Liver Disease: Long-Term Follow-Up With Magnetic Resonance Imaging and Magnetic Resonance Angiography. EXP CLIN TRANSPLANT 2016; 17:115-118. [PMID: 28004998 DOI: 10.6002/ect.2016.0024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We report a case of a 62-year-old woman who received a liver transplant 19 years previously for end-stage liver disease due to hereditary hemorrhagic telangiectasia and fibropolycystic liver disease. During long-term follow-up 8 years after the liver transplant, de novo vascular lesions were detected with magnetic resonance imaging and magnetic resonance angiography. Hepatic vascular lesions had slowly progressed, despite no symptoms. To our knowledge, there are few reports in the English literature of de novo vascular lesions after liver transplant in patients with hepatic telangiectasias.
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Affiliation(s)
- Sila Ulus
- From the Department of Radiology, Acibadem University School of Medicine, Istanbul, Turkey
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Pulmonary contraindications, indications and MELD exceptions for liver transplantation: a contemporary view and look forward. J Hepatol 2013; 59:367-74. [PMID: 23557870 DOI: 10.1016/j.jhep.2013.03.026] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 03/21/2013] [Accepted: 03/22/2013] [Indexed: 12/11/2022]
Abstract
Pulmonary concerns in liver transplant candidates have intraoperative and outcome implications. Evolving MELD exception policies address transplant priority for problems such as hepatopulmonary syndrome, portopulmonary hypertension, and hemorrhagic hereditary telangiectasia. Other pulmonary issues such as refractory hepatic hydrothorax, advanced chronic obstructive lung disease (including alpha-1 antitrypsin deficiency) and indeterminate pulmonary nodules may affect liver transplant consideration. Herein, we discuss current pulmonary-related contraindications, indications and MELD exception policies for liver transplantation, suggesting future considerations.
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Cag M, Audet M, Saouli AC, Odeh M, Ellero B, Piardi T, Woehl-Jaeglé ML, Cinqualbre J, Wolf P. Successful liver transplantation for Rendu-Weber-Osler disease, a single centre experience. Hepatol Int 2011; 5:834-40. [PMID: 21484125 DOI: 10.1007/s12072-011-9259-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2010] [Accepted: 01/25/2011] [Indexed: 11/26/2022]
Abstract
UNLABELLED BACKROUNDS/PURPOSE: Hereditary hemorrhagic telangiectasia or Rendu-Weber-Osler is an autosomal dominant inherited disorder characterized by arteriovenous malformations and telangiectasia that may affect the nose, skin, lungs, brain and gastrointestinal tract. Liver involvement of the disease has been described to be responsible of biliary tract necrosis, high cardiac output and portal hypertension, due to intra-hepatic vascular shunts. We aimed to present four cases of successful orthotopic liver transplantations in this indication performing our modified Piggy-back technique. PATIENTS AND METHODS Between 2002 and 2008, four patients have been diagnosed for Rendu-Weber-Osler disease and underwent liver transplantation. Three of them suffered from high cardiac output with heart failure, two presented HBV infection and one patient suffered from renal failure requiring a liver-kidney transplantation. We performed our modified Piggy-back technique for liver implantation, which consists to clamp selectively the hepatic veins during the hepatectomy, without venous bypass, the retro-hepatic vena cava is preserved. RESULTS No hemodynamic concerns disturbed the surgery and no massive transfusions were needed. The liver replacement corrected the cardiac insufficiency due to high cardiac output for the three patients. At present, the four patients are getting well. CONCLUSIONS Despite new advances in immunotherapy for the medical treatment of Rendu-Weber-Osler disease, liver transplantation remains the curative option for hepatic based-hereditary hemorrhagic telangiectasia.
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Affiliation(s)
- Murat Cag
- Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre, Strasbourg, France,
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Hepatic arteriovenous malformations from hereditary hemorrhagic telangiectasia: treatment with liver transplantation. Dig Dis Sci 2010; 55:3059-62. [PMID: 20844961 DOI: 10.1007/s10620-010-1353-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2010] [Accepted: 07/14/2010] [Indexed: 12/09/2022]
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Mavrakis A, Demetris A, Ochoa ER, Rabinovitz M. Hereditary hemorrhagic telangiectasia of the liver complicated by ischemic bile duct necrosis and sepsis: case report and review of the literature. Dig Dis Sci 2010; 55:2113-7. [PMID: 19757046 DOI: 10.1007/s10620-009-0968-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2009] [Accepted: 08/24/2009] [Indexed: 02/06/2023]
Affiliation(s)
- Anastasios Mavrakis
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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13
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Dupuis-Girod S, Chesnais AL, Ginon I, Dumortier J, Saurin JC, Finet G, Decullier E, Marion D, Plauchu H, Boillot O. Long-term outcome of patients with hereditary hemorrhagic telangiectasia and severe hepatic involvement after orthotopic liver transplantation: a single-center study. Liver Transpl 2010; 16:340-7. [PMID: 20209594 DOI: 10.1002/lt.21990] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatic involvement occurs in up to 74% of patients with hereditary hemorrhagic telangiectasia (HHT) and is characterized by a spectrum of arteriovenous malformations. Three different types of intrahepatic shunting may be present: hepatic artery to hepatic veins, hepatic artery to portal vein, and portal vein to hepatic vein. Hepatic involvement in HHT may lead to biliary ischemia, portal hypertension, or high-output cardiac failure (HOCF). Orthotopic liver transplantation (OLT) has been proposed as the only definitive curative treatment. The aim of this study was to evaluate the long-term outcome of patients with hepatic involvement due to HHT after OLT with respect to mortality, cardiac and hepatic status, epistaxis, and quality of life. Patients with HHT and severe hepatic vascular malformations who underwent OLT in the Lyon Liver Transplant Unit (LLTU) from 1993 to 2007 were followed at the LLTU and the French Reference Center for HHT. Quality of life was evaluated with the Short Form 36 questionnaire. There were 13 patients who fulfilled the entry criteria of the study (12 women and 1 man). The mean age at the time of OLT was 51.8 years (range = 33-65 years). Indications for OLT were cardiac failure (n = 9), biliary necrosis (n = 2), both cardiac failure and biliary necrosis (n = 1), and hemobilia (n = 1). The mean duration of follow-up was 109 months (range = 1-200 months). Twelve patients (92.3%) are still alive. For the 9 patients with HOCF, the mean cardiac index decreased from 5.4 L/minute/m(2) before OLT to 3.0 L/minute/m(2) after OLT. No severe hepatic complications were observed after OLT. Nine of the surviving patients (75%) experienced dramatic improvements in epistaxis and quality of life, including an ability to undertake more physical activity. In conclusion, OLT is an important therapeutic option for patients with HHT who have severe hepatic involvement. In the reported cohort, the mortality after OLT for this indication was low.
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Affiliation(s)
- Sophie Dupuis-Girod
- Service de Génétique et Centre de Référence pour la Maladie de Rendu-Osler, Lyon, France.
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Sabbà C, Pompili M. Review article: the hepatic manifestations of hereditary haemorrhagic telangiectasia. Aliment Pharmacol Ther 2008; 28:523-33. [PMID: 18573106 DOI: 10.1111/j.1365-2036.2008.03775.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Liver involvement in hereditary haemorrhagic telangiectasia is mainly characterized by vascular malformations, such as telangiectasies and arteriovenous shunts, which are found in up to 80% of patients. AIM To analyse the current knowledge and controversies regarding the epidemiological, pathological, clinical, diagnostic and therapeutic aspects of liver involvement in hereditary haemorrhagic telangiectasia. Methods Systematic survey analysis of the indexed studies dealing with the above mentioned topics. RESULTS No more than 8% of patients with hepatic vascular abnormalities will have a symptomatic liver disease, mainly consisting in high-output heart failure, portal hypertension or biliary disease. CONCLUSIONS Colour Doppler ultrasonography is a non-invasive, highly accurate and relatively low-cost procedure for the screening of liver involvement in patients with hereditary haemorrhagic telangiectasia; computed tomography, magnetic resonance imaging and angiography can be reserved for the characterization of focal lesions and the study of severely ill patients in whom invasive therapeutic procedures are advisable. Patients with asymptomatic liver involvement should not receive any treatment, while the therapeutic options for symptomatic patients include treatment of the specific complication, invasive procedures for shunt reduction and liver transplantation. The newly developed antiangiogenetic therapies appear to be very promising, but still require further evaluation in clinical trials.
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Affiliation(s)
- C Sabbà
- Unit of Internal Medicine, Department of Internal Medicine and Public Health, Interdepartmental HHT Centre, University of Bari, Bari, Italy.
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15
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Buonamico P, Suppressa P, Lenato GM, Pasculli G, D'Ovidio F, Memeo M, Scardapane A, Sabbà C. Liver involvement in a large cohort of patients with hereditary hemorrhagic telangiectasia: echo-color-Doppler vs multislice computed tomography study. J Hepatol 2008; 48:811-20. [PMID: 18321607 DOI: 10.1016/j.jhep.2007.12.022] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2007] [Revised: 11/15/2007] [Accepted: 12/14/2007] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIMS Hepatic arterio-venous malformations (HAVMs) have been found in 74% of hereditary hemorrhagic telangiectasia (HHT) patients with multislice CT (MSCT). This single-blind study aimed to compare the diagnostic accuracy of echo-color-Doppler with MSCT and identify the most sensitive ultrasound criteria indicating hepatic shunts. METHODS One hundred and fifty-three HHT patients were systematically screened for HAVMs by biological tests, abdominal MSCT and echo-color-Doppler. Twenty-five normal subjects and 15 cirrhotic patients were also included as control groups. Both intrahepatic ("color spots" and hypervascularization) and extrahepatic parameters (diameter, flow velocity and tortuosity of hepatic artery and diameter and flow velocity of portal/hepatic vein) were utilized. "Color-spots" are defined as subcapsular vascular spots with a high-velocity arterial blood flow and low resistivity index and can identify extremely small HAVMs. RESULTS CT was positive in 128/153 (84%) patients and Doppler color spots were found in 131/153 (86%) patients. The sensitivity, specificity and diagnostic accuracy of "color spots" compared to MSCT were 95.3%, 68.0% and 91.8%, respectively. The "color-spot" showed a greater correlation to CT (V(index)=0.655; p<0.0001) than extrahepatic criteria (V=0.317). In 20/29 (69%) subjects, echo-color-Doppler, confirmed by CT, identified the third criterion for definite HHT diagnosis. CONCLUSIONS Intrahepatic criteria was superior to extrahepatic criteria for identification of HAVMs. A new Doppler parameter ("color-spots") with an optimal accuracy for detecting HAVMs is proposed for easy periodic screening of HHT patients.
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Affiliation(s)
- Paolo Buonamico
- Unit of Internal Medicine, Department of Internal Medicine and Public Health, Interdepartmental HHT Centre, University of Bari-Policlinico, Piazza Giulio Cesare 11, Bari, Italy
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16
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Scelzo C, Greco S, Bonanni L, Di Cocco P, D'Angelo M, Laurenzi C, Pisani F, Famulari A, Orlando G. The role of liver transplantation in the treatment of hereditary hemorrhagic telangiectasia: a short literature review. Transplant Proc 2007; 39:2045-2047. [PMID: 17692689 DOI: 10.1016/j.transproceed.2007.05.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The liver is involved in up to 73% of patients suffering from hereditary hemorrhagic telangiectasia (HHT), but only some of them become symptomatic. Although management is often conservative, sometimes a more aggressive approach is required. The role of surgery is still undefined. Open ligation, banding, or closure of the arteriovenous malformation feeding artery have been proposed but rejected, as they are followed by an unacceptably high incidence of complications, derived from ischemia of the biliary tree. Orthotopic liver transplantation (OLT) has been successfully attempted in 28 patients with cardiac, biliary, or portal hypertension as well as mixed clinical presentations. Twenty-four were alive at time of data collection. Cardiovascular and pulmonary functions have improved after the operation in most cases. Intrahepatic relapse of the hallmark lesion of the disease (telangiectasia and arterovenous malformation) has been recently described in two cases. OLT represents a valuable therapeutic option for hepatic-based HHT, provided early diagnosis and referral to a specialized unit.
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Affiliation(s)
- C Scelzo
- School of Medicine, Tor Vergata University of Rome, Rome, Italy
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17
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Sabbà C, Pasculli G, Lenato GM, Suppressa P, Lastella P, Memeo M, Dicuonzo F, Guant G. Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers. J Thromb Haemost 2007; 5:1149-57. [PMID: 17388964 DOI: 10.1111/j.1538-7836.2007.02531.x] [Citation(s) in RCA: 121] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK-1 (HHT2) gene now enables a genotype-phenotype correlation. OBJECTIVE To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers. METHODS A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest-abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype-phenotype correlations were established. RESULTS PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1. CONCLUSIONS Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.
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Affiliation(s)
- C Sabbà
- Department of Internal Medicine and Public Health, University of Bari, Bari, Italy.
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Abstract
Liver involvement in hereditary hemorrhagic telangiectasia (HHT) consists of extensive intrahepatic vascular malformations associated with blood shunting (arteriovenous, arterioportal and/or portovenous). It is a rare disorder that nevertheless can result in significant systemic and hepatobiliary abnormalities. Although hepatic vascular malformations are present in a majority of patients with HHT, symptoms occur in a only a minority with a clear predominance for the female gender. Symptoms from liver vascular malformations are often misdiagnosed and this can lead to potentially harmful interventions. In this review article, clinical findings of liver involvement in HHT and their pathophysiology are discussed as well as diagnostic methodologies, therapies used and their outcome. Data presented is based on a review of the literature performed in October 2006 using the following MEDLINE search terms: (hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL]) AND (liver OR hepatic [ALL]). Papers were considered if they were published in English and if they included specific cases that were sufficiently described.
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Affiliation(s)
- Guadalupe Garcia-Tsao
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine and VA CT Healthcare System, 333 Cedar Street - 1080 LMP, P.O. Box 208019, New Haven, CT 06520, USA.
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Lerut J, Orlando G, Adam R, Sabbà C, Pfitzmann R, Klempnauer J, Belghiti J, Pirenne J, Thevenot T, Hillert C, Brown CM, Gonze D, Karam V, Boillot O. Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry. Ann Surg 2007; 244:854-62; discussion 862-4. [PMID: 17122610 PMCID: PMC1856634 DOI: 10.1097/01.sla.0000247258.35406.a4] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a rare disease characterized by the presence of arteriovenous malformations. Hepatic involvement can lead to life-threatening conditions. MATERIAL AND METHODS Forty patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation in the treatment of the hepatic disease form. Indications for transplantation were classified according to Garcia-Tsao: cardiac failure (14 patients), biliary necrosis causing hepatic failure (12 patients), severe portal hypertension (5 patients), cardiac failure and biliary necrosis (6 patients), cardiac failure and portal hypertension (2 patients), and cardiac failure associated with biliary necrosis and portal hypertension (1 patient). Eighteen (81%) of 22 patients had pulmonary artery hypertension. Twelve (30%) patients had pretransplant hepatic interventions. Follow-up was complete for all patients with a mean of 69 months (range, 0-230 months). RESULTS One-, 5- and 10-year actuarial patient and graft survival rates are 82.5%. Six of the 7 pretransplant procedures performed on the hepatic artery were severely complicated. Cardiovascular function documented in 24 patients improved in 18 patients and remained stable in 5 patients; 1 patient died perioperatively of acute heart failure. Twenty-four (60%) patients had post-transplant complications, all but one occurring within the first 4 posttransplant months. Seven (17.5%) patients died perioperatively, 6 of them due to bleeding and 1 due to cardiac failure; 1 (2.5%) patient died late due to chronic rejection. There were 2 possible recurrences. Quality of life markedly improved in all 32 surviving patients. CONCLUSION The results of the largest reported transplant series in the treatment of hepatic-based HHT are excellent. Elimination of hepatobiliary sepsis and reversal of cardiopulmonary changes dramatically improve quality of life of the recipients. LT should be proposed earlier in the course of symptomatic hepatic HHT presenting with life-threatening conditions. Palliative interventions, especially on the hepatic artery, should be avoided in view of their high (infectious) complication rate.
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Affiliation(s)
- Jan Lerut
- Liver Transplant Unit, University Hospital St. Luc, Brussels, Belgium.
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Abstract
BACKGROUND Hereditary haemorrhagic telangiectasia (HHT) is a systemic autosomal dominant vascular disease. Although the clinical picture is that of a chronic disabling disease, vascular malformations can suddenly lead to life-threatening conditions. AIM To assess the frequency and type of emergency acute complications in HHT. DESIGN Retrospective case-note review. METHODS From August 2000 to December 2004, our specialized HHT centre saw 139 patients (74 males, 65 females, mean age 45.5 years, range 14-77) with a definite diagnosis of HHT. We reviewed their clinical files and recorded all visits for acute complications (massive nosebleeds, haematemesis, melaena, haematochezia, haemothorax, haemoptysis, TIA/ischaemic stroke, haemorrhagic stroke, brain abscess). RESULTS Fifty patients (35.9%) had at least one acute complication. There were a total of 93 visits potentially involving the emergency department. Most commonly, patients sought urgent medical attention for nosebleeds and gastrointestinal bleeding (63.4%), but there were also disorders of the brain, lung, heart and liver. DISCUSSION Acute complications of HHT are not uncommon and can be severe and wide-ranging. Physicians should be aware of HHT and its major complications, as a prompt diagnosis is essential to direct patients to the most appropriate therapies, and to suggest screening for visceral involvement in their relatives.
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Affiliation(s)
- M Gallitelli
- Department of Internal Medicine and Public Health, Section of Internal Medicine, Bari, Italy
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Affiliation(s)
- C Sabbà
- Clinica Medica A.Murri, University Interdepartmental HHT Center, DIMIMP-University of Bari, Bari, Italy.
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Thevenot T, Vanlemmens C, Di Martino V, Becker MC, Denue PO, Kantelip B, Bresson-Hadni S, Heyd B, Mantion G, Miguet JP. Liver transplantation for cardiac failure in patients with hereditary hemorrhagic telangiectasia. Liver Transpl 2005; 11:834-838. [PMID: 15973723 DOI: 10.1002/lt.20463] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver involvement in hereditary hemorrhagic telangiectasia may lead to high-output cardiac failure. Few data have been reported on orthotopic liver transplantation (OLT) for these patients. In this paper, we describe two patients treated by OLT as a salvage procedure for cardiac failure, and we review literature on this subject. Our two patients resumed normal cardiac function after OLT. This procedure appears to be a promising therapy with good long-term results despite dissection difficulties encountered due to the collateral arterial network reorganization.
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Affiliation(s)
| | | | | | | | | | | | | | - Bruno Heyd
- Digestive Surgery Unit, Hôpital Jean Minjoz, Besançon, France
| | - Georges Mantion
- Digestive Surgery Unit, Hôpital Jean Minjoz, Besançon, France
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