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DOI: 10.1055/s-2001-15969
Die Hereditäre Hämorrhagische Teleangiektasie (Morbus Osler-Rendu-Weber) und ihre Manifestation an der Leber
Prof. Dr. F. H. Caselitz zum 80. Geburtstag gewidmetHepatic involvement in hereditary hemorrhagic teleangiectasiaPublication History
28.8.2000
2.10.2000
Publication Date:
31 December 2001 (online)

Zusammenfassung
Der M. Osler (Hereditäre Hämorrhagische Teleangiektasie, HHT) ist eine autosomal-dominant vererbte Erkrankung, die mit vielgestaltigen Gefäßfehlbildungen einhergeht. Die genetische Ursache dieser Erkrankung liegt in unterschiedlichen Defekten von Bindungsproteinen (Endoglin, Activin Receptor-like Kinase 1), die Anteile des Rezeptors für Transforming Growth Factor β darstellen. Von den Gefäßfehlbildungen können auch der Gastrointestinaltrakt und insbesondere die Leber betroffen sein. Der Genlokus für die hepatische Manifestation des M. Osler ist bisher nicht bekannt.
Die Gefäßmalformationen führen zu verschiedenen Shuntformen im Bereich der Leber und können im Erwachsenenalter zu unterschiedlichen Komplikationen wie Herzinsuffizienz, Pfortaderhochdruck und hepatischer Enzephalopathie führen. Als Screeningverfahren zur Frage einer Leberbeteiligung bei Patienten mit M. Osler ist die Farb-Doppler-Sonographie Methode der Wahl. In seltenen Fällen sind die o. g. Komplikationen der Leberbeteiligung konservativ nicht befriedigend zu behandeln. Für diese Patienten stehen interventionelle (Embolisation) und operative (Ligatur der Art. hepatica, Lebertransplantation) Therapieverfahren zur Verfügung. Da der Stellenwert der einzelnen Therapieverfahren nicht festgelegt ist, sollten diese Patienten an einem Zentrum vorgestellt werden, welches alle Therapieverfahren anbieten kann.
Hepatic involvement in hereditary hemorrhagic telangiectasia
M. Osler (Hereditary Hemorrhagic Telangiectasia, HHT) is an autosomal dominant inherited disease, with various vascular malformations. The genetic cause of this disease lies in different defects of transmembrane proteins (endoglin, activin receptor like-kinase 1) that can be defined as components of the receptor complex for transforming growth factor β (TGF β).
Vascular malformations include the gastrointestinal tract and especially the liver. The location of mutations encoding hepatic involvement of M. Osler still remains unknown.
These vascular malformations may lead to different shunts in the liver and can result to different complications like cardiac-insufficiency, portal hypertension and hepatic encephalopathy in adulthood.
Color Doppler sonography is the method of choice for screening patients with M. Osler - suspected of having hepatic involvement.
As in rare events conservative treatment of complications of hepatic involvement fail, embolization of the hepatic artery as minimal invasive therapy, surgical ligation of the A. hepatica and liver transplantation are possible treatment options. As there are only limited experiences with these therapeutic procedures patients with liver involvement should be treated at a center, where all therapy options are available.
Schlüsselwörter
M. Osler - Hereditäre hämorrhagische Teleangiektasie - Leber - Embolisation - Sonographie
Key words
M. Osler - Hereditary Hemorrhagic Telangiectasia - Liver - Embolization - Sonography
Literatur
- 1
Guttmacher A E, Marchuk D A, White R IJ.
Hereditary hemorrhagic telangiectasia.
N Engl J
Med.
1995;
333
918-924
MissingFormLabel
- 2
Shovlin C L, Letarte M.
Hereditary haemorrhagic telangiectasia and pulmonary
arteriovenous malformations: Issues in clinical management and review of
pathogenic
mechanisms.
Thorax.
1999;
54
714-729
MissingFormLabel
- 3 Rhiede U N, Schaefer H E, Klein P J. Störungen des Stofftransportes. Rhiede UN,
Schaefer, HE, Wehner H. Allgemeine und spezielle
Pathologie 1989: 362
MissingFormLabel
- 4
Snyder L H, Doan C A.
Clinical and experimental studies in human inheritance: Is
the homozygous form of multiple telangiectasia lethal?.
J Lab Clin
Med.
1944;
29
1211-1216
MissingFormLabel
- 5
Muller J -Y, Michailov T, Izrael V, Ernard J.
Maladie de Rendu-Osler dans une grande famille
saharienne.
Nouv Presse
Med.
1978;
7
1723-1725
MissingFormLabel
- 6
Plauchu H, de
Chadarevian J P, Bideau A, Robert J M.
Age-related clinical profile of hereditary hemorrhagic
telangiectasia in an epidemiologically recruited population.
Am J Med
Genet.
1989;
32
291-297
MissingFormLabel
- 7
Gallione C J, Klaus D J, Yeh E Y. et al .
Mutation and expression analysis of the endoglin gene in
hereditary hemorrhagic telangiectasia reveals null alleles.
Hum
Mutat.
1998;
11
286-294
MissingFormLabel
- 8
McAllister K A, Grogg K M, Johnson D W. et al .
Endoglin, a TGF-beta binding protein of endothelial cells, is
the gene for hereditary haemorrhagic telangiectasia type 1.
Nat
Genet.
1994;
8
345-351
MissingFormLabel
- 9
Haitjema T, Westermann C J, Overtoom T T. et al .
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu
disease): New insights in pathogenesis, complications, and
treatment.
Arch Intern
Med.
1996;
156
714-719
MissingFormLabel
- 10
Vincent P, Plauchu H, Hazan J. et al .
A third locus for hereditary haemorrhagic telangiectasia maps
to chromosome 12q (published erratum appears in Hum Mol Genet
1995;4:1243).
Hum Mol
Genet.
1995;
4
945-949
MissingFormLabel
- 11
Johnson D W, Berg J N, Baldwin M A. et al .
Mutations in the activin receptor-like kinase 1 gene in
hereditary haemorrhagic telangiectasia type 2.
Nat
Genet.
1996;
13
189-195
MissingFormLabel
- 12
Nikolopoulos N, Xynos E, Vassilakis J S.
Familial occurrence of hyperdynamic circulation status due to
intrahepatic fistulae in hereditary hemorrhagic
telangiectasia.
Hepatogastroenterology.
1988;
35
167-168
MissingFormLabel
- 13
Piantanida M, Buscarini E, Dellavecchia C. et al .
Hereditary haemorrhagic telangiectasia with extensive liver
involvement is not caused by either HHT1 or HHT2.
J Med
Genet.
1996;
33
441-443
MissingFormLabel
- 14
Caselitz M, Wagner S, Chavan A. et al .
Clinical outcome of transfemoral embolisation in patients
with arteriovenous malformations of the liver in hereditary haemorrhagic
telangiectasia (Weber-Rendu-Osler
disease).
Gut.
1998;
42
123-126
MissingFormLabel
- 15
White R I
Jr, Lynch-Nyhan A, Terry P. et al .
Pulmonary arteriovenous malformations: Techniques and
long-term outcome of
embolotherapy.
Radiology.
1988;
169
663-669
MissingFormLabel
- 16
Graf C, Perrett G, Torner J.
Bleeding from cerebral arteriovenous malformations as part of
their natural history.
J
Neurosurg.
1983;
58
331-337
MissingFormLabel
- 17
Kirchner J, Zipf A, Dietrich C F. et al .
Universal organ involvement in Rendu-Osler-Weber disease:
Interdisciplinary diagnosis and interventional therapy.
Z
Gastroenterol.
1996;
34
747-752
MissingFormLabel
- 18
Cloogman H M, DiCapo R D.
Hereditary hemorrhagic telangiectasia: Sonographic findings
in the
liver.
Radiology.
1984;
150
521-522
MissingFormLabel
- 19
Derauf B J, Hunter D W, Sirr S A. et al .
Peripheral embolization of diffuse hepatic arteriovenous
malformations in a patient with hereditary hemorrhagic
telangiectasia.
Cardiovasc Intervent
Radiol.
1987;
10
80-83
MissingFormLabel
- 20
Gothlin J H, Nordgard K, Jonsson K, Nyman U.
Hepatic telangiectasia in Osler’s disease treated with
arterial embolization. Report of 2 cases.
Eur J
Radiol.
1982;
2
27-30
MissingFormLabel
- 21
Michaeli D, Ben-Bassat I, Miller H I, Deutsch V.
Hepatic telangiectases and portosystemic encephalopathy in
Osler-Weber- Rendu
disease.
Gastroenterology.
1968;
54
929-932
MissingFormLabel
- 22
Reilly P J, Nostrant T T.
Clinical manifestations of hereditary hemorrhagic
telangiectasia.
Am J
Gastroenterol.
1984;
79
363-367
MissingFormLabel
- 23
Christian H A.
Osler: Recollections of an undergraduate medical student at
Johns Hopkins.
Arch Intern
Med.
1949;
84
77-83
MissingFormLabel
- 24
Martini G A.
The liver in hereditary haemorrhagic teleangiectasia: An
inborn error of vascular structure with multiple manifestations: A
reappraisal.
Gut.
1978;
19
531-537
MissingFormLabel
- 25
Ballauff A, Koletzko S.
Hereditary hemorrhagic telangiectasia with juvenile polyposis
- coincidence or linked autosomal dominant inheritance?.
Z
Gastroenterol.
1999;
37
385-388
MissingFormLabel
- 26
Kolarz G, Pietschman H.
Osler’s disease. Clinical results of 24 cases with
special reference to liver findings.
Wien Z Inn
Med.
1972;
53
17-25
MissingFormLabel
- 27
Sackier J M, Dawson P, Allison D, Spencer J.
An unusual angiogram in a patient with gastrointestinal
bleeding.
Clin
Radiol.
1990;
41
425-426
MissingFormLabel
- 28
Blobe G C, Schiemann W P, Lodish H F.
Role of transforming growth factor beta in human
disease.
N Engl J
Med.
2000;
342
1350-1358
MissingFormLabel
- 29
Daly J J, Schiller A L.
The liver in hereditary hemorrhagic telangiectasia
(Osler-Weber-Rendu disease).
Am J
Med.
1976;
60
723-726
MissingFormLabel
- 30
Bjoro K, Schrumpf E, Elgjo K, Kolmanskog F.
Monstrous ascites in hereditary haemorrhagic
telangiectasia.
Scand J
Gastroenterol.
1995;
30
92-24
MissingFormLabel
- 31 Caselitz M. Morbus Osler. Gebel M. Gastroenterologische und
hepatologische Sonographie Berlin,
Blackwell; 1999,: 50-51
MissingFormLabel
- 32
Weik C, Johanns W, Janssen J, Greiner L.
The liver and hereditary hemorrhagic
telangiectasia.
Z
Gastroenterol.
2000;
38
31-37
MissingFormLabel
- 33
Buscarini E, Buscarini L, Civardi G. et al .
Hepatic vascular malformations in hereditary hemorrhagic
telangiectasia: Imaging findings.
Am J
Roentgenol.
1994;
163
1105-1110
MissingFormLabel
- 34
Ouchi K, Matsubara S, Mikuni J. et al .
The radiologic presentation of Osler-Weber-Rendu disease of
the liver.
Am J
Gastroenterol.
1994;
89
425-428
MissingFormLabel
- 35
Varma D G, Schoenberger S G, Kumra A, Agrawal N, Robinson A E.
Osler-Weber-Rendu disease: MR findings in the
liver.
J Comput Assist
Tomogr.
1989;
13
134-135
MissingFormLabel
- 36
Chavan A, Galanski M, Wagner S. et al .
Hereditary hemorrhagic telangiectasia: Effective protocol for
embolization of hepatic vascular malformations -experience in five
patients.
Radiology.
1998;
209
735-739
MissingFormLabel
- 37
Allison D J, Jordan H, Hennessy O.
Therapeutic embolisation of the hepatic artery: A review of
75
procedures.
Lancet.
1985;
1
595-599
MissingFormLabel
- 38
Brohee D, Franken P, Fievez M. et al .
High-output right ventricular failure secondary to hepatic
arteriovenous microfistulae. Selective arterial embolization
treatment.
Arch Intern
Med.
1984;
144
1282-1284
MissingFormLabel
- 39
Roman C F, Cha S D, Incarvito J, Cope C, Maranhao V.
Transcatheter embolization of hepatic arteriovenous fistula
in Osler- Weber-Rendu disease - a case
report.
Angiology.
1987;
38
484-488
MissingFormLabel
- 40
Whiting J HJ, Morton K A, Datz F L, Patch G G, Miller F JJ.
Embolization of hepatic arteriovenous malformations using
radiolabeled and nonradiolabeled polyvinyl alcohol sponge in a patient with
hereditary hemorrhagic telangiectasia: Case report.
J Nucl
Med.
1992;
33
260-262
MissingFormLabel
- 41
Odorico J S, Hakim M N, Becker Y T. et al .
Liver transplantation as definitive therapy for complications
after arterial embolization for hepatic manifestations of hereditary
hemorrhagic telangiectasia.
Liver Transpl
Surg.
1998;
4
483-490
MissingFormLabel
- 42
Trotter J F, Suhocki P V, Lina J R. et al .
Hereditary hemorrhagic telangiectasia causing high output
cardiac failure: Treatment with transcatheter embolization.
Am J
Gastroenterol.
1998;
93
156-171
MissingFormLabel
- 43
Jackson J E.
Hepatic vascular malformations in hereditary hemorrhagic
telangiectasia: Treatment with embolization
(letter).
Radiology.
1999;
213
927-928
MissingFormLabel
- 44
Stockx L, Raat H, Caerts B. et al .
Transcatheter embolization of hepatic arteriovenous fistulas
in Rendu- Osler-Weber disease: A case report and review of the
literature.
Eur J
Radiol.
1999;
9
1434-1437
MissingFormLabel
- 45
Zentler-Munro P L, Howard E R, Karani J, Williams R.
Variceal haemorrhage in hereditary haemorrhagic
telangiectasia.
Gut.
1989;
30
1293-1297
MissingFormLabel
- 46
Bourgeois N, Delcour C, Deviere J. et al .
Osler-Weber-Rendu disease associated with hepatic involvement
and high output heart failure.
J Clin
Gastroenterol.
1990;
12
236-238
MissingFormLabel
- 47
Miller F JJ, Whiting J H, Korzenik J R, White R I.
Caution with use of hepatic embolization in the treatment of
hereditary hemorrhagic telangiectasia
(letter).
Radiology.
1999;
213
928-930
MissingFormLabel
- 48
Radtke W E, Smith H C, Fulton R E, Adson M A.
Misdiagnosis of atrial septal defect in patients with
hereditary telangiectasia (Osler-Weber-Rendu disease) and hepatic arteriovenous
fistulas.
Am Heart
J.
1978;
95
235-242
MissingFormLabel
- 49
Neumann U P, Knoop M, Langrehr J M. et al .
Effective therapy for hepatic M. Osler with systemic
hypercirculation by ligation of the hepatic artery and subsequent liver
transplantation.
Transpl
Int.
1998;
11
323-326
MissingFormLabel
- 50
Zieren J, Buttemeyer R, Muller J M.
Adjustable „banding” of the hepatic artery in
treatment of shunt-induced heart failure in Osler-Rendu-Weber
disease.
Chirurg.
1998;
69
639-641
MissingFormLabel
- 51
Boillot O, Bianco F, Viale J P. et al .
Liver transplantation resolves the hyperdynmic circulation in
hereditary hemorrhagic telangiectasia with hepatic
involvement.
Gastroenterology.
1999;
116
187-192
MissingFormLabel
- 52
Bauer T, Britton P, Lomas D. et al .
Liver transplantation for hepatic arteriovenous malformation
in hereditary haemorrhagic telangiectasia.
J
Hepatol.
1995;
22
586-590
MissingFormLabel
- 53
Mendoza A, Oliff S, Elias E.
Hereditary haemorrhagic telangiectasia and secondary biliary
cirrhosis.
Eur J Gastroenterol
Hepatol.
1995;
7
999-1002
MissingFormLabel
- 54
Saxena R, Hytiroglou P, Atillasoy E O. et al .
Coexistence of hereditary hemorrhagic telangiectasia and
fibropolycystic liver disease.
Am J Surg
Pathol.
1998;
22
368-372
MissingFormLabel
Anschrift für die Verfasser
Dr. Martin Caselitz
Medizinische Hochschule Hannover
Zentrum Innere
Medizin
Abteilung Gastroenterologie und Hepatologie
Carl-Neuberg-Straße 1
30625 Hannover
Email: Caselitz.Martin@mh-hannover.de