Diagnostic and Interventional Radiology in the Management of Post–Liver Transplant Vascular Complications

Orthotopic liver transplantation (OLT) is the definitive therapy for patients with end-stage liver disease or acute liver failure. OLT is the second most common type of solid-organ transplant, accounting for 22.8% (8,906 in total) of all organs transplanted in the United States in 2020. ¹ Recipient demographic data on OLT recipients have shown a shift to patients with older age, higher illness severity (i.e., Model for End-Stage Liver Disease [MELD] scores), and higher prevalence of obesity and diabetes. ¹ Regardless, the evolution of surgical technique and postoperative care since the inception of OLT over 50 years ago has led to reduced morbidity and mortality despite sicker patients being treated. ¹

Despite these achievements, OLT continues to have a high rate of complications (25–30%) impacting patient long-term morbidity and mortality. ² Biliary complications, such as bile leaks and biliary strictures, are among the most common with an incidence from 15 to 25%. ³ Postoperative infections, fluid collections, graft rejection, and posttransplant lymphoproliferative disorder are also common post-OLT complications. Vascular complications represent a significant portion of post-OLT complications with an incidence of 7 to 15%. ² Bleeding, stenosis, and thrombosis can arise at any of the vascular anastomotic sites with the potential to result in graft loss and mortality. ⁴ Improvements in the diagnosis and management of vascular complications following liver transplantation have contributed significantly to improving patient and graft survival rates.

Although surgery historically has been the first choice for addressing post-OLT complications, the advancement of imaging-guided minimally invasive techniques has drastically changed this approach. Interventional radiologists now play a vital role in liver transplant programs by treating posttransplant complications with endovascular and percutaneous procedures that improve graft and patient survival while avoiding surgical revision and/or retransplantation. This article will give an overview of the imaging features of common vascular complications in post-OLT patients and the role of interventional radiology in their management.

Surgical Technique Overview

OLT is a complex procedure that requires multiple anastomoses between donor and recipient's hepatic arteries, portal vein (PV), inferior vena cava (IVC), and biliary system. Multiple reconstruction techniques can be used for each anastomosis, and it is important to understand each patient's particular surgical anatomy prior to reviewing imaging or planning an intervention. Most commonly, the hepatic arterial, biliary, and PV anastomoses are completed in an end-to-end fashion. The hepatic arterial anastomosis is the most frequent site of surgical variation; however, it is typically formed in end-to-end fashion from the donor proper hepatic artery to the recipient hepatic artery ( Fig. 1 ). The donor's common bile duct is typically anastomosed to the recipient's common hepatic duct, and the donor gallbladder is removed. ⁵ Several hepatic venous outflow reconstruction techniques have been described, including the conventional approach with separate suprahepatic and infrahepatic IVC anastomoses, “piggyback” technique, and, more recently, a side-to-side cavocavostomy method ( Fig. 2 ). ⁶ The latter two approaches use a common patch for the hepatic veins (HVs) at their confluence. In the absence of pretransplant PV occlusion, the portal anastomosis is created end-to-end between donor and recipient PVs ( Fig. 3 ).

Fig. 1.

Recipient hepatic artery to donor hepatic artery end-to-end anastomosis. 1—Donor right hepatic artery, 2—Donor left hepatic artery, 3—Donor proper hepatic artery, 4—Recipient proper hepatic artery, 5—Recipient gastroduodenal artery, 6—Recipient common hepatic artery, 7—Recipient splenic artery, 8—Recipient left gastric artery.

Fig. 2.

Inferior vena cava anastomosis techniques in liver transplant. ( a ) Conventional approach with two end-to-end anastomoses between the suprahepatic inferior vena cava and infrahepatic inferior vena cava, which involves explanting the recipient liver along with retrohepatic inferior vena cava. ( b ) The piggyback technique where the recipient inferior vena cava is left in place with an end-to-side anastomosis between the donor suprahepatic cava and recipient hepatic vein and oversewing of the donor infrahepatic vena cava. 1—Recipient suprahepatic IVC, 2—Donor inferior vena cava, 3—Recipient inferior vena cava, 4—Donor hepatic vein confluence. 5—Recipient hepatic vein confluence.

Fig. 3.

End-to-end portal venous anastomosis between donor and recipient portal veins. 1—Donor portal vein, 2—Recipient portal vein, 3—Recipient superior mesenteric vein, 4—Recipient splenic vein.

Hepatic Artery Complications

Arterial complications post-OLT have a higher likelihood of graft loss and occur more frequently than venous complications. ² The hepatic artery is the most common vessel implicated, with thrombosis, stenosis, and pseudoaneurysm representing the major etiologies complicating graft function. ⁵ As the hepatic artery is the sole vascular supply of the posttransplant biliary tree, ischemic biliary complications frequently result from hepatic artery compromise. ⁵

Hepatic Artery Thrombosis

Hepatic artery thrombosis (HAT) is the most severe, post-OLT vascular complication occurring in 4 to 12% of adult OLT and up to 40% in pediatric OLT, with mortality rates as high as 75%. ^{5 7} Preexisting hepatic artery stenosis (HAS), prolonged graft ischemic time, acute rejection, increased donor age, hypercoagulability, prior transarterial chemoembolization (TACE), recipient tobacco use, and donor–recipient hepatic artery mismatch are some of the identified risk factors for HAT. ^{2 5 8 9} Early HAT (within 30 days of OLT) has a high mortality risk associated with early graft loss. Although surgical revascularization or retransplantation remains important option, endovascular revascularization of early HAT is an alternative therapy associated with lower morbidity and mortality. ⁷ Endovascular procedures for HAT sometimes serve as a bridge for retransplantation but can be definitive therapy. ^{5 8 9} Due to the development of collateral circulation, late HAT (>30 days) can sometimes be better tolerated than early HAT, although up to two-thirds of cases may still require adjunct biliary interventions like percutaneous biliary or abscess drainage. ^{2 5}

The presence of recurring bacteremia; biliary complications including delayed bile leak, duct strictures, and biliary necrosis; and the development of sepsis or fulminant hepatic necrosis are highly suggestive of HAT. HAT may also present asymptomatically with mild transaminitis. ^{5 8} Doppler ultrasound (DUS) has high accuracy for detecting HAT by observing no flow in the hepatic arteries, the disappearance of a previously normal hepatic artery diastolic flow, or even a decrease in the expected arterial upstroke during systole. ⁵ Failure to visualize hepatic artery flow on DUS may occur in the setting of low cardiac output or arterial vasospasm. Cross-sectional imaging modalities like computed tomography angiography (CTA) and magnetic resonance angiography (MRA) can help confirm the diagnosis of HAT. ^{10 11 12} By using microbubble contrast, contrast-enhanced ultrasound (CEUS) can reveal an arterial flow not visualized on prior DUS. ¹⁰ CTA with pre- and post-contrast multiphasic imaging with thin-slice angiography in the early arterial phase can reveal hepatic artery filling defects or a sharp discontinuation of the hepatic artery caliber. ¹¹ Magnetic resonance cholangiopancreatography (MRCP) can be performed along with MRA which can detect biliary complications associated with HAT and help guide their management. ¹¹ Selective catheter-directed arteriography remains the gold standard to confirm HAT.

Endoluminal management of early HAT can be achieved by transcatheter intra-arterial thrombolysis (IAT) with or without mechanical thrombectomy. ^{5 8 9} Daily angiography is used to monitor the progression of thrombolysis, and the patient is closely monitored in the intensive care unit for bleeding or complications. As HAT can often arise secondary to an underlying HAS at the anastomotic site, a subsequent intervention like endovascular angioplasty with stent placement is often necessary after clot dissolution. ^{5 8 9} In a retrospective study of 26 patients who received IAT for HAT following liver transplantation, 42% of patients experienced major complications and 46% had technical successful recanalization of the hepatic artery. In patients who were treated with IAT for early HAT, 50% of these complications involved major bleeding, while only 9% of late HAT patients experienced this complication. ¹³

Hepatic Artery Stenosis

The second most common vascular complication following OLT is HAS with an incidence of 1.2 to 9.5%. ⁵ The stenosis most frequently develops at the site of anastomosis, with risk factors including graft rejection, size mismatch, surgical technique, and clamp injury. ⁵ The median time of HAS presentation is 3 to 7 months post-OLT, and may be suggested by elevations in bilirubin and alkaline phosphatase. ⁵ DUS can reveal HAS by depicting turbulent flow at or distal to the stenotic segment with an elevated peak systolic velocity (PSV) greater than 200 cm/s. DUS in the hepatic artery branches downstream to the stenosis may display a parvus tardus waveform or a low resistive index (RI) less than 0.5 ( Fig. 4a ). CTA can confirm and further characterize the severity and extent of the stenosis and aid in treatment planning ( Fig. 4b ). MRA/MRCP can also help confirm the diagnosis of HAS, as well as detect associated ischemic biliary complications. ^{5 10}

Fig. 4.

A 61-year-old male presents 3 months after liver transplant with abnormal liver function tests. ( a ) Duplex ultrasound reveals donor right hepatic artery with low resistive index (RI) of 0.53 and parvus tardus waveform (white arrowhead) concerning for hepatic artery stenosis. ( b ) Computed tomography angiography with maximum intensity projection demonstrates high-grade focal stenosis (straight black arrow) at the hepatic artery anastomosis. Biliary stent (curved black arrow), donor celiac artery (curved white arrow), and donor superior mesenteric artery (straight white arrow). Common hepatic angiograms before ( c ) and after ( d ) balloon-expandable stent placement shows the resulting luminal gain in the previously narrowed anastomotic segment (straight black arrow). ( e ) Duplex ultrasound following the procedure depicts normalization of the RI to 0.81 with improved waveform and brisk systolic upstroke (white arrowhead).

Endovascular interventions including angioplasty and/or stent placement are the preferred method of HAS treatment ( Fig. 4c–e ). Anatomic considerations such as a single focal stenosis in a straight segment of the hepatic artery are more likely to be successfully treated by endovascular methods, whereas multifocal stenosis or associated kinks in the hepatic artery increase the risk of complications and may be better served by surgical revision. ¹⁴ One treatment challenge in HAS is the lack of appropriately sized/designed stents for this location, and balloon-expandable stents are commonly used. ^{5 15} Although endovascular intervention for HAS has been associated with favorable outcomes, complications like vasospasm, dissection, and pseudoaneurysm can occur in 5.7 to 9% of cases. ⁵ Recent studies have reported better outcomes and patency rates in patients receiving stent placement compared to angioplasty alone. In a 2018 retrospective study of 30 patients who received primary arterial stent placement for HAS, the technical success rate was 97% with a primary patency rate of 90% at 1-year follow-up. Most of these cases utilized balloon-expandable stents (77%) and all patients had administration of intra-arterial nitroglycerin and heparin prior to stent deployment. ¹⁶

Hepatic Artery Pseudoaneurysm

Although a pseudoaneurysm in the hepatic artery is an uncommon complication following OLT (estimated incidence of 0.3–2.6%), it presents with a significant risk of rupture. ¹⁷ They tend to occur at the hilum or anastomotic site and can occasionally coexist with hepaticobiliary or portobiliary fistulas and present with hemobilia. ⁵ Intrahepatic pseudoaneurysms have been associated with posttransplant biopsies and percutaneous transhepatic cholangiography, while extrahepatic pseudoaneurysms have been associated with anastomotic or HAS/HAT treatment complications. ⁵ Ruptured extrahepatic pseudoaneurysms have a higher rate of mortality at 78 versus 50% in intrahepatic lesions. ⁵ While both pseudoaneurysms can present with elevated liver function tests (LFTs), extrahepatic pseudoaneurysms are more likely to present with fever, sepsis, and upper gastrointestinal or intra-abdominal bleeds. Ultrasound may depict a hypoechoic lesion on grey scale imaging with bidirectional flow (“yin-yang” sign) seen on color flow imaging. Dynamic contrast-enhanced CT or MR can confirm hepatic artery pseudoaneurysms with the lesion following blood pool Hounsfield units on arterial and venous phases ( Fig. 5a ). Definitive diagnosis can be achieved with angiography ( Fig. 5b, c ). Endovascular treatment options depend on the size and location of the pseudoaneurysm. Extrahepatic lesions arising from the main hepatic artery are often treated with stent grafts to exclude the aneurysm while preserving hepatic artery flow to the liver ( Fig. 5d ). Distal intrahepatic lesions are often treated with embolization. ⁵

Fig. 5.

A 60-year-old man with liver transplant complicated by biliary stricture requiring multiple endoscopic retrograde cholangiopancreatographies (ERCPs) with hemobilia found to be arising from a hepatic artery pseudoaneurysm. (a) Coronal computed tomography angiography shows a pseudoaneurysm (straight white arrow) from the common hepatic artery (straight black arrows), which is confirmed with common hepatic digital subtraction angiography ( b and c ) with early arterial jet (white open arrow in b ) and delayed arterial contrast filling the pseudoaneurysm (straight white arrow in c ). Indwelling hepatic artery stent (black open arrow) from prior failed treatment. ( d ) Repeat treatment with balloon-expandable stent graft (black arrowhead) and resolution of the pseudoaneurysm.

Nonocclusive Hepatic Artery Hypoperfusion Syndrome

Nonocclusive hepatic artery hypoperfusion syndrome (NHAHS), also known as splenic steal, is a vascular complication occurring early after OLT with an incidence between 0.6 and 10.1%. ^{18 19} The syndrome arises due to increased preferential flow to the splenic arteries with poor perfusion of the hepatic arteries and consequential hepatic ischemia. The liver attempts to offset this decreased arterial perfusion by increasing its portal venous flow; however, this leads to both increased sinusoidal pressures and decreased release of adenosine. As adenosine is an important vasodilator, its absence results in vasoconstriction, which further exacerbates hepatic arterial hypoperfusion. ¹⁸ Splenomegaly and elevated hepatic arterial resistance are two of the risk factors associated with the development of NHAHS. ¹⁸ Patients may present asymptomatically, with elevated LFTs, or with persistent ascites, thrombocytopenia, or cholestasis from intrahepatic bile duct damage. ^{5 18}

Liver ultrasound can reveal periportal edema and increased liver parenchymal echogenicity in NHAHS. ¹⁸ On color Doppler, one may observe a consistently elevated hepatic artery RI greater than 1 ( Fig. 6a ), a low (or reversed) hepatic artery diastolic velocity, or elevated flow velocities in the splenic artery and PV with increased portal flow volume. ¹⁸ Angiography is gold standard to confirm the diagnosis of NHAHS ( Fig. 6b ). It may reveal the slow filling of hepatic arteries relative to the rapid opacification of splenic arteries in the absence of anatomical defects such as HAS or thrombosis. ^{18 19 20} The increased portal flow seen in NHAHS may be observed with abnormal hepatic artery filling during portal venous phase on CT. ¹⁹

Fig. 6.

A 54-year-old male with liver transplant presents with elevated liver function tests concerning for nonocclusive hepatic artery hypoperfusion syndrome. ( a ) Duplex ultrasound 3 days posttransplant shows loss of diastolic flow of left hepatic artery and resistive index of 1 (white arrowhead). ( b ) Digital subtraction celiac angiography demonstrates hepatic arterial hypoperfusion (straight black arrow) and dominant flow into the splenic artery (straight white arrow). ( c ) Digital subtraction celiac angiography following coil embolization (black arrowhead) of the splenic artery demonstrates restored flow in the hepatic artery (straight black arrow).

Transcatheter splenic artery embolization (SAE) is the first-line intervention for NHAHS due to its low risk and potential for immediate improvement of hepatic arterial flow and portal hyperperfusion. ^{5 19 20} Proximal SAE ( Fig. 6c ) is preferred as collateral flow to the spleen is preserved, reducing likelihood of splenic infarction compared to distal SAE. ^{20 21} Splenic artery ligation or banding at the time of transplant can serve as prophylactic procedures in high-risk patients, while splenectomy is reserved for severe cases due to its higher rates of postoperative portal thrombosis and infection. ^{18 19 21} NHAHS is a preventable cause of early graft loss after OLT; however, due to its insidious presentation, it must be identified and treated promptly.

Portal Vein Complications

Post-OLT PV complications are less frequent than hepatic arterial complications and include portal vein thrombosis (PVT) and portal vein stenosis (PVS). PV complications are more common in pediatric transplantations and split liver and liver donor OLT. ^{4 22 23} The higher incidence in pediatric patients has been theorized to result from their smaller PVs, short graft pedicles, greater size mismatching, and graft types used in this population. ²³ Patients with PVS and PVT may present asymptomatically with alterations in LFTs, or with symptoms of portal hypertension like ascites, gastroesophageal varices, and splenomegaly. ²⁴

Portal Vein Stenosis

PVS is typically a late complication presenting more than 6 months after OLT with an incidence of 1 to 5%. ⁵ Nearly all PVS cases occur at the anastomosis site due to fibrosis with neointimal hyperplasia. ²⁵ Early PVS (within 6 months) is less common and often occurs due to technical complications during transplantation including donor and recipient PV size mismatch, malrotation of vessels, or kinking of the PV due to a long vessel stump. ¹²

Although PVS can present as an asymptomatic imaging finding or with mildly elevated LFTs, PVS often presents with signs of portal hypertension such as varices, ascites, or splenomegaly. Severe PVS can lead to PVT, uncompensated portal hypertension, lower limb edema, and even hepatic graft failure. ²⁴ On DUS, an elevated peak PV velocity of greater than 125 cm/sec or a three- to fourfold increase in PV velocity at the stenosis are 73% sensitive and 95 to 100% specific in detecting significant PVS. ^{25 26} PVS can be confirmed noninvasively by contrast-enhanced CT or MRI ( Fig. 7a ). ²⁵ The gold standard tool in PVS diagnosis remains direct portal venography ( Fig. 7b ), as it can both directly visualize the anastomosis and also help determine whether the stenosis has clinical significance. The latter can be accomplished by obtaining portal pressure gradient measurements across the stenotic segment, with a gradient greater than 5 mm Hg generally considered clinically significant. ^{2 25 26} Direct portal venography does require percutaneous transhepatic (most common), transsplenic (less common), or transjugular (rare) access, with the associated bleeding risks, and thus is typically reserved for situations in which therapeutic intervention is likely.

Fig. 7.

A 48-year-old male with history of alcoholic cirrhosis presents 3 months after liver transplant with elevated liver function tests. ( a ) Post-contrast computed tomography of the abdomen shows severe stenosis at the portal vein anastomotic site (straight black arrow). ( b ) Transhepatic portal venogram confirms portal vein stenosis with an elevated pressure gradient of 6 mm Hg (straight black arrow). ( c ) Portal vein balloon angioplasty (straight white arrow) of the stenotic anastomotic segment. ( d ) Following angioplasty, repeat portal venogram shows good luminal gain (straight black arrow) and improved pressure gradient to 2 mm Hg. No further intervention was considered necessary.

Treatment of PVS is based in part on clinical presentation. Asymptomatic patients with mild stenosis and normal LFTs can forego intervention in favor of surveillance imaging. For patient with more severe stenosis and symptoms, first-line therapy is angioplasty ( Fig. 7c ) with or without stent placement. This is typically performed through a percutaneous transhepatic approach and less commonly through a transjugular approach. ²⁵ Increasingly, transsplenic approaches have been utilized to reduce risk of liver graft injury. ^{27 28} Stenting with noncovered, bare metal stents is generally reserved for recurrent or residual stenosis. Long-term patency data for portal venous stents are limited, and the role of long-term anticoagulation in these patients is not clearly defined. ^{2 25} Complications, although infrequent, are most commonly related to the required percutaneous access and include hemoperitoneum and hemothorax. ²⁵

Portal Vein Thrombosis

PVT is a rare complication of OLT (1–4% of transplants) with 80% of cases presenting less than a month from transplant. ² Proposed contributors to early PVT include suboptimal venous grafts, hypercoagulable states, portal venous stasis, and underlying anatomical defects including PVS or kinking. ^{2 25} Early PVT cases are also more likely to result in eventual graft loss. Late-onset PVT (>1 month) can be a consequence of initial PVS or iatrogenic thrombosis from angioplasty or stenting for PVS. ²⁹ These cases can present clinically similar to PVS with DUS revealing lack of Doppler color flow and echogenic thrombus within the PV. Contrast-enhanced CT or MR is used for confirmation and treatment planning.

Surgical options for PVT include surgical thrombectomy and revision of the anastomosis, sometimes requiring bypass grafts. ² Due to the low incidence of PVT following OLT, literature on catheter-directed therapy is currently limited to case reports and small series studies leading to difficulty drawing definitive conclusions on success rates, complications, and optimal transcatheter approaches. ^{2 25} Endovascular management such as thrombectomy or catheter-directed thrombolysis is typically done through either a transjugular intrahepatic or direct transhepatic approach. ²⁶ A transsplenic approach has also been utilized in case studies when the thrombosis prevents direct access to the intrahepatic PV. ^{30 31} Advantages and disadvantages to each approach are discussed elsewhere. ^{2 25 26} Similar to HAT, adjunctive angioplasty or stent placement is often required following removal of clot to treat underlying PVS. ²⁹

Inferior Vena Cava and Hepatic Vein Complications

Venous outflow obstruction due to stenosis or thrombosis can occur at the level of the HV or IVC. These complications are rare (<2%), but incidence varies with the type of anastomosis and graft used. ³² The reported incidence with bicaval and cavocavostomy techniques is 1 to 2%, while the piggyback technique is around 4%. ^{2 5} Stenosis in the early postoperative period often occurs due to technical factors such as size mismatch, twisting of the veins, or dissection. Late stenosis is more common and is most often due to perivascular fibrosis or intimal hyperplasia but may also result from compression or twisting of a growing split graft. ³³

Clinical manifestations of venous outflow obstruction at the HV or the IVC, above the HV anastomosis, involve symptoms of hepatic congestion including ascites, varices, hepatosplenomegaly, pleural effusions, abdominal pain, and abnormal LFTs. With IVC stenosis below the HV anastomosis, lower limb edema or ascites may be the presenting symptoms. Duplex ultrasound is the preferred, noninvasive tool to screen for suspected venous outflow obstruction that can reveal decreased mean velocities in the PV and HV, along with dampening of the normal post-OLT bi- or triphasic waveform to a monophasic pattern. ⁵ CT and MRI can also help identify anastomotic stenosis and other ancillary findings. ² Transjugular hepatic venography presents relative low risk, can confirm suspected stenosis, and allows for transstenotic pressure gradient measurement which can help guide the need for therapeutic intervention. Although a threshold gradient has not clearly been established, greater than 5 to 10 mm Hg is often considered an indication to treat the stenosis. ^{2 26 34}

Treatment of IVC or HV stenosis often begins with prolonged percutaneous balloon angioplasty (PTA), though PTA alone can require multiple treatments to achieve long-term patency. ³⁵ A transjugular approach is typically used, although adjunct transhepatic access may also be required in the setting of high-grade stenosis or occlusion. With a “piggy-back” anastomosis, transfemoral access may occasionally be preferred. Of note, PTA in the IVC is generally less effective because of the vein's high elasticity and prolonged balloon inflation should be performed with caution due to risk of dropping cardiac output. ⁵ Stenting is another option for HV and IVC stenosis and is the preferred first-line option by some operators due to high recurrence rates following PTA. ³⁶ Stents with larger interstices are recommended to avoid disrupting blood flow over the HV or its branches. ³⁴ Slightly oversized stents can be used to prevent stent migration in the IVC, the most feared complication. ⁵

IVC thrombosis is a rare complication of IVC stenosis (0.3% of cases) that has severe implications in the early postoperative period with a high incidence of graft loss and mortality. ^{26 37} If IVC thrombosis occurs late, collaterals may have developed, and the patient may be relatively asymptomatic. Thrombus generally forms below the stenotic anastomosis and can be treated with thrombolytic therapy or mechanical thrombectomy. Nonetheless, thrombolytic infusion in the early postoperative period should be used with caution due to risks of stimulating anastomotic bleeding. Unfortunately, immediate postprocedure thrombosis often requires retransplantation. ³³

Conclusion

Vascular complications following OLT impact graft survival and represent a significant cause of morbidity and mortality in transplant recipients. Diagnostic and interventional radiology play a fundamental role in the identification and management of these conditions. As many of these complications can present with subtle or nonspecific symptoms or laboratory abnormalities, diagnostic imaging is crucial to detect vascular abnormalities and plan treatment. Duplex ultrasound is routinely employed as a screening tool utilized for close follow-up after OLT and may be the first sign of a vascular complication. While CT and MR can help confirm the preliminary DUS findings or reveal ancillary abnormalities missed by DUS, angiography and venography remain the gold standard for definitive diagnosis. Although surgical options remain important, increasingly endovascular treatments such as angioplasty, stent placement, and thrombolysis are preferred for their minimally invasive therapeutic benefit. Multidisciplinary management incorporating interventional radiologists and transplant surgeons remain key to treating these complex vascular complications to maximize graft and patient survival.