Ischemic Bile Duct Injury

Published on 19/07/2015 by admin

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Last modified 22/04/2025

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 Solitary or multifocal strictures of variable length

• Cholangiography: Gold standard for diagnosis

image Appearance may be identical to PSC with “beading” of biliary tree (alternating stenosis, normal ducts, and mild dilatation)
image Biliary casts appear as filling defects within duct lumen
• CT: Scattered irregular biliary dilatation with bile duct wall thickening and hyperenhancement

image Presence of intrahepatic biloma or liver infarct should prompt careful assessment for HAT/HAS
image Bile duct casts appear as intraductal hyperdense material
image CT not sensitive for early stage ischemic injury
• MR: Linear high T1 signal intensity may be visualized within dilated central ducts, characteristic of biliary cast

PATHOLOGY

• Classically due to hepatic artery thrombosis, but possible without arterial compromise (ischemic-type biliary lesions)
• Also associated with prolonged warm and cold ischemic time, ABO incompatibility, and chronic rejection

CLINICAL ISSUES

• Initial treatment: Endoscopic or percutaneous dilatation/stenting of strictures and clearing of biliary casts
• Roux-en-Y hepaticojejunostomy for extrahepatic strictures unresponsive to dilatation/stenting
• Retransplantation may be necessary in patients with secondary biliary cirrhosis, recurrent cholangitis, or progressive cholestasis
image
(Left) Coronal CECT MIP reconstruction in a liver transplant patient demonstrates abrupt occlusion of the hepatic artery image near its origin from the celiac artery.

image
(Right) Cholangiogram in the same patient demonstrates features of ischemic cholangiopathy due to hepatic artery occlusion, including a dominant stricture in the common duct image and irregularity of the intrahepatic ducts.
image
(Left) ERCP of a patient with jaundice after liver transplant shows a filling defect in the hilum, representing a hilar biliary cast image, and diffusely irregular intrahepatic ducts. The patient’s course was complicated by portal vein thrombosis and rejection, but the hepatic artery was patent on US.

image
(Right) T1WI FS MR of the same patient shows a typically high signal cast image at the duct bifurcation. Multiple ischemic and immunological insults may result in the strictures and casts that are characteristic of ischemic cholangiopathy.

TERMINOLOGY

Synonyms

• Ischemic cholangitis, ischemic cholangiopathy

Definitions

• Nonanastomotic biliary strictures in liver allograft originally described in setting of hepatic artery thrombosis (HAT) or stenosis (HAS), but now known to occur due to a wide variety of other microangiopathic and immunological injuries

IMAGING

General Features

• Best diagnostic clue

image Nonanastomotic biliary strictures in liver allograft
• Location

image Can involve intrahepatic &/or extrahepatic ducts
image Predominant involvement of middle 1/3 of common bile duct and hepatic duct confluence > intrahepatic ducts
image 2 common patterns

– Strictures beginning at hilum and extending peripherally
– Multiple scattered intrahepatic strictures
• Morphology

image Can be solitary or multifocal strictures
image Variable length: Short or long segment

Radiographic Findings

• Cholangiography (ERCP or PTC) is gold standard for diagnosis of ischemic cholangitis

image Cholangiographic appearance may be nearly identical to primary sclerosing cholangitis
image Luminal irregularity of bile ducts with beaded appearance (alternating sites of stenosis, normal ducts, and mild dilatation)

– Strictures evolve over time, beginning as sites of irregularity and developing into fibrotic strictures
– Ductal narrowing with upstream dilatation
– Rare diffuse duct necrosis and biliary sloughing
image Biliary casts appear as filling defects within duct lumen
image May demonstrate communication of bile ducts with intrahepatic bilomas

CT Findings

• Scattered irregular biliary dilatation with bile duct wall thickening and hyperenhancement

image Presence of intrahepatic biloma or liver infarct in post-transplant setting should prompt careful assessment of hepatic artery for HAT/HAS

– Doppler US to screen, then CTA confirmation if Doppler positive
image Bile duct casts, highly suggestive of ischemic cholangiopathy, appear as linear hyperdense material within bile duct

– May not be readily distinguishable from stone on CT (both may appear hyperdense)
image Biliary necrosis, debris, and bilomas with advanced ischemia (particularly in setting of HAS/HAT)
• CT not sensitive for early stage ischemic-type biliary lesions (ITBL)

image Transplanted liver may not develop biliary dilatation despite severe ductal stenosis
image If high clinical suspicion for ITBL, proceed to cholangiography (ERCP, PTC, or MRCP)
• CTA can show hepatic artery narrowing or thrombosis

MR Findings

• Strong correlation between MRCP and cholangiography

image High sensitivity, specificity, and predictive values for evaluation of ischemic-type biliary injury
• Hepatobiliary contrast agents (i.e., Eovist) can be used for cholangiographic images in hepatobiliary phase

image Most often utilized to evaluate for strictures at hepaticojejunostomy
• T2WI, MRCP, and T1WI C+ Eovist cholangiographic images demonstrate luminal irregularity, stenosis, and scattered biliary ductal dilatation
• May be associated with T2-hyperintense intrahepatic bilomas or liver infarcts
• Linear high T1 signal intensity may be visualized within dilated central ducts, characteristic of biliary cast

image Extremely uncommon in absence of ischemic cholangiopathy and virtually diagnostic
image MR allows distinction between cast (T1 hyperintense) and stones (hypointense on all pulse sequences)
• Advantage of noninvasively evaluating other biliary complications (anastomotic stricture, stones, leak, etc.)
• MRA can show hepatic artery thrombosis or stenosis

Ultrasonographic Findings

• Grayscale ultrasound

image Poor sensitivity for early stage ischemic-type biliary injury
image May show intrahepatic ductal dilatation and thickening
image Biliary casts appear as echogenic material within dilated bile ducts
image Advanced biliary ischemia due to HAT or HAS may result in presence of intrahepatic fluid collections (bilomas)
image Extrahepatic biliary dilatation is nonspecific finding in post-transplant liver and does not necessarily imply ischemic cholangiopathy

– Nonobstructive dilatation of extrahepatic ducts (without intrahepatic biliary dilatation) may be due to papillary dyskinesia or discrepancy between size of donor and recipient ducts
• Pulsed Doppler

image Evaluate for evidence of HAT or HAS

– Hepatic artery stenosis (or chronic HAT with collaterals)

image Turbulent flow within hepatic artery with focal aliasing at site of stenosis
image Usually occurs at or near anastomosis and affects 11% of patients (mean 3 months after surgery)
image Tardus parvus waveform (systolic acceleration time > 100 msec): Rounded spectral Doppler waveforms with delayed systolic upstrokes
image Intrahepatic arterial resistive index < 0.5
image Peak anastomotic systolic velocity > 200 cm/sec
image Post-anastomotic hepatic arterial peak systolic velocity < 48 cm/sec (may increase specificity)
– Hepatic artery thrombosis: Failure to visualize hepatic artery on US

image CTA or MRA required for confirmation, as poor acoustic windows, arterial spasm, low cardiac output, or severe parenchymal edema can simulate thrombosis on US
image Usually occurs weeks to months after surgery

Imaging Recommendations

• Best imaging tool

image Cholangiography (PTC, ERCP): Gold standard for diagnosis and allows intervention
image MRCP best noninvasive test for changes in biliary tree
image US followed by CTA/MRA for assessment of HAS/HAT
• Protocol advice

image  

DIFFERENTIAL DIAGNOSIS

Anastomotic Biliary Ductal Stricture

• Most often at choledocho-choledochal (orthotopic transplantation) or choledochojejunal anastomosis (living donor)
• Not associated with additional strictures in biliary tree

Ascending Cholangitis

• Pyogenic infection of biliary tree due to biliary obstruction
• Biliary dilatation with duct wall thickening and heterogeneous parenchymal enhancement

Primary Sclerosing Cholangitis

• May be virtually identical to ischemic cholangitis on cholangiography or MRCP
• May recur years following liver transplantation, whereas ischemic cholangiopathy tends to develop in first few months after transplant

Choledocholithiasis

• Alteration in bile composition after liver transplantation increases risk of developing biliary stones
• Stones may be mistaken for biliary cast on CT or ERCP
• Biliary sludge, necrotic debris, or pneumobilia can mimic biliary stones
• Low signal on all MR pulse sequences

PATHOLOGY

General Features

• Etiology

image Nonanastomotic biliary strictures initially described in setting of hepatic artery thrombosis and were thought to be a merely ischemic entity

– Early thrombosis of hepatic artery disrupts blood supply before transcapsular collaterals have time to form, resulting in ischemic bile duct injury
– However, can be seen in absence of arterial compromise, with ischemic cholangiopathy in absence of hepatic artery thrombosis or stenosis described as ischemic-type biliary lesions (ITBL)

image ITBL now believed to be multifactorial
image Risk factors

– Ischemic injury

image Prolonged warm ischemic time (during organ harvesting or implantation)
image Prolonged cold ischemic time
image Reperfusion injury
image Disturbed hepatic arterial blood flow (thrombosis, stenosis, increased resistance)
– Immunological injuries

image ABO incompatibility
image Preexisting autoimmune disease (primary sclerosing cholangitis, autoimmune hepatitis, etc.)
image CMV infection
image Chronic rejection (direct injury to biliary epithelium + indirect injury due to arteriopathy)
– Bile-salt-induced injury

image Alteration in bile composition and flow
image Biliary epithelial cells are more prone to ischemic injury

– Solely supplied by hepatic artery, with 50% of hepatic artery blood flow destined for bile ducts via peribiliary plexus (microvascular network supplying bile ducts)
– Intrinsic susceptibility to reperfusion/reoxygenation injury
image Hereditary hemorrhagic telangiectasia, radiation, polyarteritis nodosa, severe atherosclerosis, and vasculitis have known associations with ischemic cholangiopathy
image Cholangiopathy after intraarterial chemotherapy, hepatic artery chemoembolization, and AIDS cholangiopathy may also result partially from ischemia

Staging, Grading, & Classification

• Classification of non-anastomotic biliary strictures (not widely used)

image Type I: Extrahepatic lesions
image Type II: Intrahepatic lesions
image Type III: Intrahepatic and extrahepatic lesions

Microscopic Features

• Ductular proliferation
• Cholestasis

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Nonspecific presentation, including abdominal discomfort, cholestasis, and fever
image ↑ γ-glutamyl transferase, ↑ alkaline phosphatase
• Other signs/symptoms

image Fever

Demographics

• Epidemiology

image Usually occurs within first 6 months after transplantation
image Incidence: 5-15% of liver allografts, but decreased compared to beginning of transplant era (∼ 30%)

Natural History & Prognosis

• Formation of biliary casts can result in “biliary cast syndrome,” with casts preventing normal bile drainage and causing biliary obstruction/infection
• Endoscopic or percutaneous dilatation and stenting of strictures have ∼ 50% success rate
• Biliary complications after liver transplant associated with increased mortality rate 

image ∼ 50% of patients will ultimately either die or require retransplantation

Treatment

• Initial treatment: Endoscopic or percutaneous dilatation/stenting of strictures and clearing of biliary casts (reported success rate of 50%) ± PTC drainage

image PTC drainage: Usually as a temporary measure
• Ursodeoxycholic acid (Ursodiol): Theoretically improves bile composition and flow, but little supportive evidence
• Roux-en-Y hepaticojejunostomy for extrahepatic strictures unresponsive to dilatation/stenting
• Retransplantation may be necessary in patients with secondary biliary cirrhosis, recurrent cholangitis, or progressive cholestasis

DIAGNOSTIC CHECKLIST

Consider

• CT and US are not sensitive for evaluation of early stage ischemic bile duct injury

image If persistent high clinical suspicion for ischemic bile duct injury, proceed to MRCP or cholangiography
• Doppler US should be performed to assess hepatic arterial patency if ischemic cholangitis is suspected, with CTA or MRA for confirmation

image CTA may provide roadmap prior to curative angioplasty of flow-limiting, arterial anastomotic stenoses

Image Interpretation Pearls

• Liver allograft may not develop biliary dilatation despite severe biliary stenosis
• Extrahepatic biliary ductal dilatation (in absence of intrahepatic ductal dilatation) is a nonspecific finding in setting of liver transplantation

image May be related to papillary dyskinesis or discrepancy between size of donor and recipient bile ducts, and is often of no clinical significance
image
(Left) Coronal MRCP MIP reconstruction in a patient with hepatic artery thrombosis demonstrates extensive irregularity throughout the biliary tree with apparent filling defects image in the central bile ducts, compatible with ischemic cholangiopathy. A biliary drainage catheter image is in place.

image
(Right) Axial T1WI MR in the same patient demonstrates diffuse biliary dilatation with extensive T1 hyperintense biliary “cast” material image distending the ducts. The biliary drainage catheter image is again noted.
image
(Left) Cholangiogram in a liver transplant patient with a known history of hepatic artery thrombosis demonstrates a classic appearance of ischemic cholangiopathy, with multiple strictures of the intrahepatic and extrahepatic ducts. The appearance is indistinguishable from primary sclerosing cholangitis.

image
(Right) Cholangiogram in a liver transplant patient with severe hepatic artery stenosis demonstrates extensive irregularity and stricturing of the biliary tree, compatible with ischemic cholangiopathy.
image
(Left) Axial CECT of a woman 4 years post liver transplant shows extensive biliary necrosis. The left bile duct image is expanded and irregular, and the right duct image is obscured by an adjacent biloma image. The patient was retransplanted.

image
(Right) MRCP of a patient post liver transplantation shows a dominant ischemic stricture image and moderate intrahepatic ductal dilatation. The hepatic artery was patent on Doppler US. Brush biopsies of the stricture were negative, and a liver biopsy showed changes compatible with ischemic reperfusion injury.
image
Axial T2WI MR in a patient with hepatic artery thrombosis demonstrates diffuse biliary dilatation with extensive T2-hypointense biliary “cast” material image distending the ducts. A biliary drainage catheter image is in place.

image
Ultrasound in a patient with hepatic artery thrombosis demonstrates a biliary drainage catheter image with echogenic biliary “cast” material image distending the ducts.
image
Cholangiogram in the same patient demonstrates subtle signs of ischemic cholangiopathy with stricture image and irregularity of the left ducts proximally.
image
Angiogram in a liver transplant patient after selective catheterization of the celiac demonstrates abrupt thrombosis image of the proximal hepatic artery at its origin from the celiac. Some perfusion of the liver is noted via collaterals image.
image
Axial CECT in a liver transplant patient 10 days after surgery demonstrates acute occlusion image of the proximal hepatic artery.
image
Axial T1WI C+ FS MR demonstrates abrupt occlusion of the hepatic artery image in a liver transplant patient.
image
Axial T1WI C+ MR in the same patient demonstrates diffuse irregular biliary dilatation related to ischemic cholangiopathy.
image
Axial CECT in a patient with hepatic artery thrombosis shows a large low-density lesion image in the liver with a branching configuration that roughly parallels the portobiliary tracts, highly suggestive of a biloma resulting from hepatic artery stenosis or thrombosis.
image
Percutaneous catheter was introduced to decompress the biloma in the same patient, with injection of the catheter opacifying nondilated ducts. However, many of the duct walls are necrotic and are surrounded by an amorphous collection image of bile and contrast medium.
image
Doppler spectra of the left hepatic artery of a 56-year-old man with elevated liver function tests post liver transplantation shows a tardus parvus waveform, a finding suggesting a proximal hepatic arterial stenosis. Angiography confirmed an arterial anastomotic stenosis, which was then angioplastied.
image
ERCP of the same patient shows subtle biliary duct stricturing and irregularity image, characteristic features of ischemic cholangiopathy. Irregularity improved with successive stent exchanges.
image
Ultrasound of a 63-year-old man 1 year post liver transplantation with an elevated alkaline phosphatase shows a biliary cast image within the right common bile duct. The hepatic artery was widely patent at Doppler and CT examinations.
image
ERCP of the same patient shows intra- image and extrahepatic biliary casts image. Note extensive intrahepatic biliary strictures and beading. Biliary ischemic injury may be due to a variety of microangiopathic and immunogenetic insults.
image
Axial CECT of a 63-year-old man with ischemic bile duct injury post transplantation shows a soft tissue attenuation cast image within dilated bile ducts. Treatment included multiple stent exchanges and cast retrieval.
image
Acute ischemic bile duct injury-induced necrosis image is shown in this liver.
image
Hematoxylin and eosin section demonstrates bile duct injury image (uneven nuclear spacing and loss of polarity) and periductal fibrosis image in chronic ischemic cholangitis.
image
Hematoxylin and eosin section demonstrates bile duct loss in chronic ischemic cholangitis. This portal tract contains hepatic artery image and portal vein image branches but lacks an identifiable bile duct profile.
image
Hematoxylin and eosin section demonstrates bile duct epithelial cell necrosis image and sloughing into the bile duct lumen image to form biliary casts in acute ischemic cholangitis.
image
Hematoxylin & eosin section demonstrates an injured bile duct with an eosinophilic biliary cast image in acute ischemic cholangitis. There is also mild portal inflammation and periductal edema image.

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