Add captions on this slide- is this from Julie Black? Provide the flow quantification.
Would replace the regional perfusion anomaly pic- it’s not really important. Why not show some cine images from the MRI on Julie Black to show the rapid progression of contrast through the arteriovenous shunts, the large hepatic arteries, and the aneurysm?
Would re-word this slide and add descriptive captions.
Need to cite the newer article by Sophie Dupuis-Girod on avastin in hht
82.5% for which time period?
Liver manifestations of hht revised
Liver manifestations of HHTQuazi Al-Tariq MDJustin McWilliams MD
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
BACKGROUNDHereditary 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 personsHHT is characterized by mucocutaneous and/or visceral angiodysplasias, which may range from telangiectasias to arteriovenous malformationsLiver involvement is common in HHT, particularly in patients with HHT type 2, with a reported prevalence of over 50% in some studies
BACKGROUNDHHT 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 communicationsBoth are associated with fibrous proliferation with preservation of the intervening parenchyma, which can give rise to pseudo- cirrhotic liver. AVM
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
CTMultiphase (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
CTArterioportal 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
CTIn 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
CTCT 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 seenMultiphase CT in patient with arterioportal shunting demonstrates evidence of portal hypertension including portal vein enlargement and ascites.
CTCT 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 effusionsMultiphase CT in patient with arteriovenous shunting demonstrates evidence of high-output cardiac failure including cardiomegaly, enlargedhepatic veins, and ascites.
CTCT 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 subtypeA macronodular liver may be seen with any of the three subtypes
USUltrasound allows rapid evaluation of the liver in HHT without ionizing radiationCommon 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.
USDoppler techniques add important information about flowdynamics, which aids in the identification of the various shunts•In cases of arterioportal shunts, one can see pulsatilehepatofugal flow within the portal system Color and spectral Doppler ultrasound images demonstrate hepatofugal portal venous flow with pulsatility, reflecting arterialization from arterioportal shunts.
USArterial 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
MRIThe 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 gradientsThe 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
MRIAlthough 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
ANGIOGRAPHYSelective 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
ANGIOGRAPHYThe 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
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
TREATMENTThe vast majority of HHT patients with liver involvement have relatively minor liver AVMs and will never be symptomaticIn <5% of HHT patients, severe liver AVMs will result in clinical complications such as those described on previous slidesMedical 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.
TREATMENTSome patients, particularly those with high-output cardiac failure from large arteriovenous shunts, may be difficult to manage with conventional medical therapiesVascular 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.
TREATMENTWhile 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 necrosisIt 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.
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.
REFERENCES Stabile Ianora, AA, Memeo, M, et al. Hereditary hemorrhagic telangiectasia: multi- detector row helical CT assessment of hepatic involvement. Radiology 2004; 230: 250- 259. 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.
CT– A macro-nodular liver may be seen in all of the above AB C A- cardiomegaly B- peribiliary cyst (arrow) C-macro-nodular liver