This presentation discusses the liver manifestations of Hereditary Hemorrhagic Telangiectasia (HHT). HHT is characterized by mucocutaneous and visceral angiodysplasias ranging from telangiectasias to arteriovenous malformations. Liver involvement is common, with over 50% prevalence in some studies. Imaging plays an important role in identifying shunt patterns and complications. Multiphase CT and Doppler ultrasound can demonstrate arteriovenous and arterioportal shunting. Treatment is tailored to clinical symptoms, with medical management preferred over embolization due to risks of hepatic necrosis. Transplantation may be considered for intractable complications such as heart failure or biliary disease.

1. Liver manifestations of HHT
Quazi Al-Tariq MD
Justin McWilliams MD

2. PURPOSE
This presentation is targeted to radiologists and interventional
radiologists who may be involved in diagnosis and treatment
of Hereditary Hemorrhagic Telangiectasia (HHT) patients
with liver involvement.
Topics to be discussed include:
 Basic pathophysiology of HHT, specifically typical shunt
mechanisms and their implications
 Multi-modality imaging findings, including CT, US,
angiography, and MRI
 Possible treatment options and the potential role of the
interventional radiologist

3. BACKGROUND
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-
Rendu Syndrome, is an autosomal dominant disorder which occurs with a
reported frequency of about 1/7,000 persons
HHT is characterized by mucocutaneous and/or visceral angiodysplasias,
which may range from telangiectasias to arteriovenous malformations
Liver involvement is common in HHT, particularly in patients with HHT type
2, with a reported prevalence of over 50% in some studies

4. BACKGROUND
HHT can be viewed as a spectrum ranging from
telangiectasias to AVMs
 Telangiectasias are focal dilatations of the
post-capillary venules, without preserved
capillaries
Telangiectasia
 AVMs are larger and represent direct arterial
to venous communications
Both are associated with fibrous proliferation
with preservation of the intervening
parenchyma, which can give rise to pseudo-
cirrhotic liver.
AVM

5. CLINICAL IMPORTANCE
Patients with HHT liver involvement are at risk for development of
congestive heart failure, portal hypertension, cholangitis, and
atypical cirrhosis
 The predominant intra-hepatic shunt determines which outcome
the patient is likely to have
 Arteriovenous shunting -> CHF
 Arterioportal shunting -> Portal hypertension
 Therefore, imaging to identify shunt patterns may allow patients
to be stratified based on their likelihood for certain outcomes
Imaging of patients with HHT and liver disease may be carried
through multiple modalities, including CT, US, MRI, and
angiography

6. CT
Multiphase (arterial, portal venous, and late
venous) CT is the preferred CT imaging
technique
 Multi-planar reformations, 3D maximum
intensity projections (MIPs), and 3D volume
rendering may be helpful
 A fourth “late arterial” or arteriolar phase,
which is acquired after a short delay (5
seconds) following the “early” arterial phase
may also be used
 Most authors feel that there is little value
added with the late arterial acquisition

7. CT
Arterioportal shunts are suggested when there is early and prolonged
enhancement of the portal vein during the arterial phase. Enhancement of
the portal vein may approach that of the aorta.
Arteriovenous shunts are thought to be present when there is opacification
of the hepatic veins during the arterial phase.
Portosystemic venous shunts are usually a microscopic phenomenon.
However, a dilated portal vein communicating with a hepatic vein branch
may sometimes be visualized on CT.
Arteriovenous shunting.
Note enhancement of the
hepatic veins (arrows)
during arterial acquisition

8. CT
In addition to shunts, other findings may be evident with multiphase CT:
 Telangiectasias may be seen as rounded, arterially enhancing peripheral
lesions, usually with a diameter of less than 10 mm. Multiple telangiectasias
may coalesce to give the appearance of what has been termed “confluent
vascular masses”
 Transient hepatic attenuation differences (THADs) are peripheral, often wedge
shaped hyper-attenuating areas on arterial phase imaging which become iso-
attenuating during the portal venous phase.
Arrow indicates multiple
telangiectasias forming a
confluent vascular mass

9. CT
CT may demonstrate other findings particular to the predominant
shunting mechanism and thus the clinical subclassification:
• In the portal hypertension group, findings of enlarged portal veins,
splenomegaly, ascites, and portosystemic collaterals may be seen
Multiphase CT in patient with arterioportal shunting demonstrates evidence of portal hypertension including portal vein enlargement and ascites.

10. CT
CT may demonstrate other findings particular to the predominant
shunting mechanism and thus the clinical subclassification:
• In the high output group, expected findings include cardiac dilatation,
enlarged hepatic veins, and pleural effusions
Multiphase CT in patient with arteriovenous shunting demonstrates evidence of high-output cardiac failure including cardiomegaly, enlarged
hepatic veins, and ascites.

11. CT
CT may demonstrate other findings particular to the predominant
shunting mechanism and thus the clinical subclassification:
• In the biliary disease group, one may be able to see biliary strictures or
peribiliary cysts
• This is the rarest subtype
A macronodular liver may be seen with any of the three subtypes

12. US
Ultrasound allows rapid evaluation of the liver in HHT without ionizing radiation
Common grey-scale findings include dilatation and tortuosity of the proper hepatic
artery and its branches, which may be seen as multiple tubular structures within the
liver with echogenic walls
 The size of the hepatic arteries is generally proportional to the amount of
arteriovenous shunting
 Other possible grey scale findings include hepatomegaly, splenomegaly, nodular
liver surface contour, and dilated portal vein (>12 mm at its mid-portion)
Grayscale and color Doppler ultrasound images demonstrate dilated hepatic artery branches and aneurysm formation in a
patient with large arteriovenous shunting.

13. US
Doppler techniques add important information about flow
dynamics, which aids in the identification of the various shunts
•In cases of arterioportal shunts, one can see pulsatile
hepatofugal flow within the portal system
Color and spectral Doppler ultrasound images demonstrate hepatofugal portal venous flow with pulsatility, reflecting arterialization from
arterioportal shunts.

14. US
Arterial velocity is increased in affected HHT
patients, while portal and hepatic veins are not
significantly different from healthy controls
• The arterial velocity is directly related to arterial
size and likely the result of increased shunting
• This does not usually translate into increased
venous velocity
– Instead of the multiphasic waveform which
varies with the cardiac cycle, a continuous
monophasic or biphasic waveform may be
seen in the hepatic veins
– This may be due to variability in the size of
the hepatic veins as well as decreased Spectral Doppler ultrasound image demonstrates
compliance of the liver secondary to continuous biphasic waveform in the left hepatic vein in
this patient with large arteriovenous shunting
increased arterial inflow

15. MRI
The role of MRI for the evaluation of the liver in HHT has significantly increased
over the last several years due to advancements in technology, including
higher field strengths, phased array coils, and high performing gradients
The goals of MR in this clinical scenario are the same as those outlined for CT
 Establish shunt pattern, assess for perfusion abnormalities, identify pertinent
findings given the subcategory of disease
 Another potential advantage of this modality is the use of flow quantification
to elicit flow dynamics and ventricular function

16. MRI
Although imaging protocols will vary, the following sequences are obtained
at the author’s institution
 Axial T1, single shot fast spin echo (SS-FSE), T2 single shot and FSE, and T2
spectral selection attenuated inversion recovery (SPAIR)
 Dynamic MRA may be obtained in a single breath hold using a T1
weighted 3D fast field echo and bolus tracking
 On a separate work station, the dynamic data sets may be used to
create multiplanar reconstructions, MIPs, and cine views
T2 image MRA
demonstrates demonstrates
regional perfusion dilated
abnormlaity tortuous MHA

17. ANGIOGRAPHY
Selective angiography with digital subtraction is rarely needed for diagnosis,
but remains an alternate method to evaluate for liver involvement in
patients with HHT
 Celiac and hepatic angiography will demonstrate arteriovenous and
arterioportal shunting as well as flow dynamics
 High volume superior mesenteric arteriography can be used in order to
visualize patency and flow direction of the portal system
Selective catheterization of
the celiac axis in a patient
with multiple arteriovenous
shunts demonstrates a
dilated, tortuous hepatic
artery, and flow reversal of
the gastroduodenal artery
due to sump effect

18. ANGIOGRAPHY
The most commonly seen angiographic finding in patients with HHT is
multiple telangiectasias/AVMs along with hepatic artery dilatation
 In patients who are symptomatic, portovenous and arterioportal shunts
could be demonstrated
 However, in cases of combined shunt types, ie. Arteriovenous and
portovenous, there is often poor visualization of the portovenous shunt
due to contrast dilution through the A-V shunts

19. TREATMENT
 In the past, hepatic arterial embolization was
used to treat mesenteric steal as well as large
arteriovenous or arterioportal shunts
 However, many of these cases were complicated
by hepatic necrosis and death
 In arteriovenous shunts, embolization can
worsen ischemia of the peribiliary plexus and
cause biliary ductal necrosis
 In arterioportal shunts, embolization of both the
arterial and portal venous supply can lead to Superselective coil embolization of several
arterioportal shunts was performed in an attempt to
widespread parenchymal necrosis ameliorate severe portal hypertension in this patient
with HHT. The patient suffered transaminitis and
 In the presence of portal to hepatic vein shunts, abdominal pain, but no noticeable improvement in
portal hypertension ensued. Hepatic arterial
the hepatic artery becomes the primary nutrient embolization in HHT patients should be undertaken
supply to the liver, thus making arterial only in very rare circumstances.
embolization even more unfavorable

20. TREATMENT
The vast majority of HHT patients with liver involvement have relatively minor liver
AVMs and will never be symptomatic
In <5% of HHT patients, severe liver AVMs will result in clinical complications such
as those described on previous slides
Medical management is first-line for liver-related complications in HHT patients
 High output cardiac failure can usually be managed by correcting anemia and
diuretic therapy, with or without anti-arrhythmics and beta blockade
 Portal hypertension is managed in the same manner as in cirrhotic patients, with
volume restriction and diuretics for ascites, and beta-blockade and endoscopic
banding for varices.

21. TREATMENT
Some patients, particularly those with high-output cardiac failure from
large arteriovenous shunts, may be difficult to manage with conventional
medical therapies
Vascular endothelial growth factor (VEGF) appears to be upregulated in
patients with HHT, making anti-VEGF therapy with bevacizumab (Avastin)
a back-up treatment option
 Published results using a regimen of 6 infusions of Avastin (5mg/kg)
over a 12 week period are very promising
 Case reports demonstrated reversal of cholestasis, cardiac failure, and ascites.
Treatment also resulted in decreased liver vascularity and volume.
Mitchell A, Adams LA, MacQuillan G, Tibballs J, vanden Driesen R,
Genentech 2012 Delriviere L. Bevacizumab reverses need for liver transplantation in
hereditary hemorrhagic telangiectasia
Liver Transpl. 2008 Feb;14(2):210-3.

22. TREATMENT
While multiple medical options exist, the definitive treatment for
symptomatic liver involvement in HHT is transplantation. 1-, 5- and 10-
year patient and graft survival are excellent (82.5%)
When a patient should be listed for transplant is debatable, but it is
generally considered for:
 Intractable heart failure
 Severe biliary disease complicated by recurrent episodes of cholangitis
 Widespread biliary necrosis
It has recently been recommended that an additional MELD score of 40
and 22 points, respectively, should be assigned to HHT patients with
acute biliary necrosis or intractable heart failure waiting for transplant.
Garcia-Tsao G, Korzenik JR, Young L, et al. Liver disease in patients
with hereditary hemorrhagic telangiectasia. N Engl J Med 2000; 343:
931–6.

23. SUMMARY
After reviewing this presentation, the viewer should have a
clearer understanding of the liver manifestations of HHT.
 A multi-modal approach can be taken by the radiologist
including CT, US, MRI, and angiography
 The clinical features typically reflect the pervasive intra-
hepatic shunt type
 Treatment is tailored to the clinical symptoms.
Complications of embolization therapy have limited its role
in favor of medical management and transplantation.

24. REFERENCES
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Garcia-Tsao G, Korzenik JR, et al. Liver disease in patients with HHT. N Eng J Med 2000;
343: 931-936.
Naganuma H, Ishida H, Niizawa M, Igarashi K, Shioya T, Masamune O. Hepatic involvement
in Osler-Weber-Rendu disease: findings on pulsed and color Doppler sonography.
AJR1995 ;165:1421 -1425
Saluja S, White, RI. Hereditary hemorrhagic telangiectasia of the liver: hyperperfusion with
relative ischemia-poverty amidst plenty. Radiology 2004; 230: 25-27.
Wu JS, Saluja S, et al. Liver involvement in hereditary hemorrhagic telangiectasia: CT and
clinical findings do not correlate in symptomatic patients. AJR 2012; 187: 399-405.
Caselitz M, Bahr MJ, et al. Sonographic criteria for the diagnosis of hepatic involvement in
HHT. Hepatology 2003, 37: 1139-1146.
Whiting JH, Korzenik, JR, et al. Fatal outcome after embolotherapy for hepatic
arteriovenous malformations of liver in two patients with HHT. JVIR 2000; 11: 855-858.

25. CT
– A macro-nodular liver may be seen in all
of the above A
B C
A- cardiomegaly B- peribiliary cyst (arrow) C-macro-nodular liver