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Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome) and Liver Vascular Malformations

  • Elisabetta Buscarini
  • Guido Manfredi
Chapter

Abstract

Liver VMs unique to HHT are diffuse and can evolve in a continuum from small telangiectases to large arteriovenous malformations, in different stages of severity. Doppler US is the ideal first line investigation for the assessment of liver VMs in HHT taking into account its safety, tolerability, low costs, accuracy for the detection of liver VMs. Caliber, course, and flow characteristics in hepatic artery, portal vein and hepatic vein as determined by Doppler US, together with parenchymal abnormalities, support either the diagnosis of liver VMs in HHT and their severity staging. Wherever expertise of Doppler ultrasound is lacking, multiphase CT is a suitable alternative to investigate symptomatic liver VMs. Echocardiography is necessary to appreciate systemic hemodynamic impact of liver VMs. Assessment of HHT patients with symptoms/signs suggestive of complicated liver VMs, and particularly if OLT is considered either for refractory portal hypertension or cardiac failure, may require a combination of contrast enhanced imaging, upper digestive endoscopy, right heart catheterization or HVPG.

Keywords

Hereditary hemorrhagic telangiectasia Vascular malformations Liver Doppler US Portal hypertension High output cardiac failure 

References

  1. 1.
    Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000;91:66–7. PubMed PMID: 10751092CrossRefPubMedGoogle Scholar
  2. 2.
    Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJ, Marchuk DA. A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet. 2004;363:852–9. PubMed PMID: 15031030CrossRefPubMedGoogle Scholar
  3. 3.
    Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, Gilbert-Dussardier B, Goizet C, Roume J, Rabilloud M, Saurin JC, Cottin V, Honnorat J, Coulet F, Giraud S, Calender A, Danesino C, Buscarini E, Plauchu H. French-Italian-Rendu-Osler Network. Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med. 2007;9:14–22. PubMed PMID: 17224686CrossRefPubMedGoogle Scholar
  4. 4.
    Buscarini E, Leandro G, Conte D, Danesino C, Daina E, Manfredi G, Lupinacci G, Brambilla G, Menozzi F, De Grazia F, Gazzaniga P, Inama G, Bonardi R, Blotta P, Forner P, Olivieri C, Perna A, Grosso M, Pongiglione G, Boccardi E, Pagella F, Rossi G, Zambelli A. Natural history and outcome of hepatic vascular malformations in a large cohort of patients with hereditary hemorrhagic teleangiectasia. Dig Dis Sci. 2011;56:2166–78.  https://doi.org/10.1007/s10620-011-1585-2. PubMed Central PMCID: PMC3112486CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Buscarini E, Danesino C, Olivieri C, Lupinacci G, De Grazia F, Reduzzi L, Blotta P, Gazzaniga P, Pagella F, Grosso M, Pongiglione G, Buscarini L, Plauchu H, Zambelli A. Doppler ultrasonographic grading of hepatic vascular malformations in hereditary hemorrhagic telangiectasia – results of extensive screening. Ultraschall Med. 2004;25:348–55. PubMed PMID: 15368138 CrossRefPubMedGoogle Scholar
  6. 6.
    Memeo M, Stabile Ianora AA, Scardapane A, Buonamico P, Sabbà C, Angelelli G. Hepatic involvement in hereditary hemorrhagic telangiectasia: CT findings. Abdom Imaging. 2004;29:211–20. PubMed PMID: 15290948CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia-Tsao G, Korzenik JR, Young L, Henderson KJ, Jain D, Byrd B, Pollak JS, White RI Jr. Liver disease in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2000;343:931–6. PubMed PMID: 11006369 CrossRefPubMedGoogle Scholar
  8. 8.
    Garcia-Pagàn JC, Buscarini E, Janssen HL, Leebeck FW, Plessier A, Rubbia-Brandt L, Senzolo M, Schouten JN, Tripodi A, Valla DC. European Association for the Study of the Liver. Vascular diseases of the liver. J Hepatol. 2016;64:179–202.  https://doi.org/10.1016/j.jhep.2015.07.040. PubMed PMID: 26516032CrossRefGoogle Scholar
  9. 9.
    Buscarini E, Danesino C, Plauchu H, de Fazio C, Olivieri C, Brambilla G, Menozzi F, Reduzzi L, Blotta P, Gazzaniga P, Pagella F, Grosso M, Pongiglione G, Cappiello J, Zambelli A. High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia. Ultrasound Med Biol. 2004;30:1089–97. PubMed PMID: 15550313 CrossRefPubMedGoogle Scholar
  10. 10.
    Gincul R, Lesca G, Gelas-Dore B, Rollin N, Barthelet M, Dupuis-Girod S, Pilleul F, Giraud S, Plauchu H, Saurin JC. Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences. Hepatology. 2008;48:1570–6. PubMed PMID: 18972447 CrossRefPubMedGoogle Scholar
  11. 11.
    Dupuis-Girod S, Ginon I, Saurin JC, Marion D, Guillot E, Decullier E, Roux A, Carette MF, Gilbert-Dussardier B, Hatron PY, Lacombe P, Lorcerie B, Rivière S, Corre R, Giraud S, Bailly S, Paintaud G, Ternant D, Valette PJ, Plauchu H, Faure F. Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output. JAMA. 2012;307:948–55. PubMed PMID: 22396517 CrossRefPubMedGoogle Scholar
  12. 12.
    Dupuis-Girod S, Buscarini E. Response to Bevacizumab for the treatment of Rendu-Osler disease—a note of caution. Liver Int. 2017;37(6):928. PubMed PMID: 28544692 CrossRefPubMedGoogle Scholar
  13. 13.
    Caselitz M, Wagner S, Chavan A, Gebel M, Bleck JS, Wu A, Schlitt HJ, Galanski M, Manns MP. Clinical outcome of transfemoral embolisation in patients with arteriovenous malformations of the liver in hereditary haemorrhagic telangiectasia (Weber-Rendu-Osler disease). Gut. 1998;42:123–6. PubMed PMID: 9505897 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, Spears J, Brown DH, Buscarini E, Chesnutt MS, Cottin V, Ganguly A, Gossage JR, Guttmacher AE, Hyland RH, Kennedy SJ, Korzenik J, Mager JJ, Ozanne AP, Piccirillo JF, Picus D, Plauchu H, Porteous ME, Pyeritz RE, Ross DA, Sabba C, Swanson K, Terry P, Wallace MC, Westermann CJ, White RI, Young LH, Zarrabeitia R, HHT Foundation International – Guidelines Working Group. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48:73–87.  https://doi.org/10.1136/jmg.2009.069013. PubMed PMID: 19553198CrossRefPubMedGoogle Scholar
  15. 15.
    Garcia-Tsao G, Gish RG, Punch J. Model for end-stage liver disease (MELD) exception for hereditary hemorrhagic telangiectasia. Liver Transpl. 2006;12(Suppl 3):S108–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Caselitz M, Bahr MJ, Bleck JS, Chavan A, Manns MP, Wagner S, Gebel M. Sonographic criteria for the diagnosis of hepatic involvement in hereditary hemorrhagic telangiectasia (HHT). Hepatology. 2003;37:1139–46. PubMed PMID: 12717395 CrossRefPubMedGoogle Scholar
  17. 17.
    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.  https://doi.org/10.1016/j.jhep.2007.12.022.CrossRefPubMedGoogle Scholar
  18. 18.
    Schelker RC, Barreiros AP, Hart C, Herr W, Jung EM. Macro- and microcirculation patterns of intrahepatic blood flow changes in patients with hereditary hemorrhagic telangiectasia. World J Gastroenterol. 2017;23:486–95. PubMed PMID: 28210085CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Buscarini E, Gebel M, Ocran K, Manfredi G, Del Vecchio Blanco G, Stefanov R, Olivieri C, Danesino C, Zambelli A. Interobserver agreement in diagnosing liver involvement in hereditary hemorrhagic telangiectasia by Doppler ultrasound. Ultrasound Med Biol. 2008;34:718–25.  https://doi.org/10.1016/j.ultrasmedbio.2007.11.007. PubMed PMID: 18207308 CrossRefPubMedGoogle Scholar
  20. 20.
    Siddiki H, Doherty MG, Fletcher JG, Stanson AW, Vrtiska TJ, Hough DM, Fidler JL, McCollough CH, Swanson KL. Abdominal findings in hereditary hemorrhagic telangiectasia: pictorial essay on 2D and 3D findings with isotropic multiphase CT. Radiographics. 2008;28:171–84.CrossRefPubMedGoogle Scholar
  21. 21.
    Buscarini E, Buscarini L, Danesino C, Piantanida M, Civardi G, Quaretti P, Rossi S, Di Stasi M, Silva M. Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family. J Hepatol. 1997;26:111–8. PubMed PMID: 9148001 CrossRefPubMedGoogle Scholar
  22. 22.
    Olivieri C, Lanzarini L, Pagella F, Semino L, Corno S, Valacca C, Plauchu H, Lesca G, Barthelet M, Buscarini E, Danesino C. Echocardiographic screening discloses increased values of pulmonary artery systolic pressure in 9 of 68 unselected patients affected with hereditary hemorrhagic telangiectasia. Genet Med. 2006;8:183–90.CrossRefPubMedGoogle Scholar
  23. 23.
    Sopeña B, Pérez-Rodríguez MT, Portela D, Rivera A, Freire M, Martínez-Vázquez C. High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Eur J Intern Med. 2013;24:30–4.CrossRefGoogle Scholar
  24. 24.
    Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001;345:325–34.CrossRefPubMedGoogle Scholar
  25. 25.
    Buscarini E, Buscarini L, Civardi G, Arruzzoli S, Bossalini G, Piantanida M. Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: imaging findings. AJR Am J Roentgenol. 1994;163:1105–10. PubMed PMID: 7976883 CrossRefPubMedGoogle Scholar
  26. 26.
    Scardapane A, Stabile Ianora A, Sabbà C, Moschetta M, Suppressa P, Castorani L, Angelelli G. Dynamic 4D MR angiography versus multislice CT angiography in the evaluation of vascular hepatic involvement in hereditary haemorrhagic telangiectasia. Radiol Med. 2012;117:29–45.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Gastroenterology and Endoscopy DepartmentHHT Reference CenterCremaItaly

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