Objectives: A hepatic vascular complication after liver transplant is a critical situation, often resulting in graft failure and potentially leading to patient death. Early diagnosis and treatment of vascular complications can provide prolonged graft survival and prohibit further complications. This study presents our experiences with endovascular treatment during the first week after liver transplant.
Materials and Methods: Between January 2012 and February 2021, 240 liver transplants were performed, with 43 patients having early endovascular treatment (37 men; mean age 27 ± 2.9 years) at a single center. Early endovascular interventions were carried out 1 to 7 days (mean ± SD of 2.7 ± 0.24 days) after transplant. Patients with vascular complications were grouped by arterial, venous, and portal complications. In addition, arterial complications were subgrouped by occlusive (hepatic artery thrombosis) and nonocclusive
(hepatic artery stenosis/splenic artery steal syndrome) complications. Patients had median follow-up of 47 ± 4 months.
Results: In the first week after liver transplant, vascular complications included splenic artery steal syndrome in 27 patients (62.7%), hepatic complications in 10 patients (23.2%) (7 with hepatic artery thrombosis, 3 with hepatic artery stenosis), hepatic venous outflow complications in 4 patients (9.3%), and portal vein complications in 2 patients (4.6%). Only 1 patient required revision surgery because of excessive arterial kinking; the remaining patients with arterial complications were successfully managed with multiple endovascular treatment attempts. Patients with splenic artery steal syndrome were treated by selective arterial embolization with coil devices. Resistivity index, peak systolic velocity of hepatic arteries, and portal vein maximal velocity significantly improved (P < .001). Patients with hepatic venous outflow and portal vein complications who had endovascular treatments and vascular structures maintained good results over follow-up.
Conclusions: Early endovascular intervention is feasible and safe for hepatic vascular complications following liver transplant, with high success treatment rates with advances in interventional radiology.
Key words : Hepatic arterial stenosis, Hepatic arterial thrombosis, Hepatic venous outflow obstruction, Liver transplantation, Portal vein stenosis
Vascular complications, especially in the early postoperative period, may cause catastrophic results, manifesting with graft failure after liver transplant (LT). Hepatic artery stenosis (HAS) and hepatic artery thrombosis (HAT), both well-recognized vascular complications, have an overall incidence varying from 2% to 15% and have higher rates with more complex surgeries in pediatric patients and living donor LT recipients.1-6 Nonocclusive hepatic artery hypoperfusion syndrome is another critical cause of graft loss in the early period after LT. Another complication, hepatic venous outflow obstruction (HVOO), is uncommon in adults. The absence of early diagnosis and treatment of HVOO may result in irreversible hepatic congestion and graft loss.7-9 Another critical and devastating vascular complication is portal vein complications associated with anastomotic portal vein stenosis (PVS) or portal vein thrombosis (PVT).10 Early diagnosis and endovascular treatment of these complications in the early period posttransplant are critical for graft survival.
A review of the literature showed that most endovascular interventions for vascular comp-lications were conducted a median of 1 to 4 months after LT.1,2,11-13 To our knowledge, there are no data on use of endovascular treatments for vascular complications (arterial, venous, and portal) during the first week after LT. Here, we described the management of these early vascular complications and demonstrated the benefits of early endovascular treatments (in the first week) after LT.
Materials and Methods
All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Between January 2012 and February 2021, 240 LTs were performed in a single center with 43 consecutive patients having early endovascular treatment (37 men; mean age of 27 ± 2.9 years). Early endovascular interventions were performed 1 to 7 days (mean of 2.7 ± 0.24 days) after LT. Among the patient group, 32 had living donor LTs and 11 had deceased donors LTs. In living donor LT, donors were related to the recipients, and the relationship between donor and recipient was up to the fourth degree. Patients with vascular complications were grouped by arterial, venous, and portal vein complications. In addition, arterial complications were subgrouped by occlusive (HAT) and nonocclusive (HAS and splenic artery steal syndrome [SASS]) complications. Early endovascular treatments included 27 SASS interventions, 10 arterial interventions, 3 hepatic vein interventions, 1 inferior vena cava (IVC) intervention, and 2 portal vein interventions. The median follow-up period was 47 ± 4 months (range, 1-96 months). Patient characteristics are listed in Table 1.
Doppler ultrasonography was a first-line imaging study performed every 12 hours in the first week after LT surgery. Arterial peak systolic velocity, end diastolic velocity, and resistive index were evaluated for each patient. For hepatic vein and portal vein evaluations, we measured velocities. Computed tomography angiography was performed when there was evidence of vascular insufficiency in the Doppler examination. After the Doppler or computed tomography angiography results were reviewed, if there was suspicion of a vascular complication, patients immediately underwent diagnostic angio-graphy.
All statistical analysis was performed with IBM SPSS statistical software version 23. Patient demographics were analyzed using descriptive statistics. We used the Wilcoxon signed-rank test to compare the peak systolic velocity, resistance index, and portal vein velocity at the time of diagnosis of SASS and after selective arterial embolization. P < .05 was considered as statistically different.
Diagnostic angiography procedures
These procedures were performed under local anesthesia and intravenous sedation. For arterial intervention, a single femoral artery wall puncture was performed using ultrasonography for sheath insertion. After aortography with a 4F to 5F pigtail catheter, we performed selective catheterization of the celiac trunk or the superior mesenteric artery with 4F to 5F shepherd hook catheter or Simmons catheter. Hepatic artery stenosis was diagnosed when the angiography showed a 50% decrease in the luminal diameter. The absence of graft flow (total occlusion) was categorized as HAT.
Interventions for hepatic artery stenosis and hepatic artery thrombosis
After the diagnostic hepatic arteriogram, we attempted to advance a 0.014- to 0.016-inch soft tip guidewire (Terumo) in a 2.4F or 2.7F microcatheter (Fast Tracker, Target Therapeutics, or Renegade HI-FLO, Boston Scientific) through the stenotic or the occluded hepatic artery. After the stenotic/occluded segment was crossed, we performed a control angiography to demonstrate the true distal hepatic artery lumen. If the hepatic artery luminal diameter was more than 50% decreased, a percutaneous transluminal angioplasty (PTA) was performed. Before PTA, heparin (100 U/kg) was administered from the arterial sheath. If the PTA was insufficient, stents were inserted (coronary stent, Boston Scientific). For patients with HAT, catheter-directed thrombolytic therapy was performed through the 4F or 5F catheter (2-4 mg of tissue plasminogen activator [tPA]). For patients with insufficient thrombolysis, an infusion catheter was placed at the thrombosed hepatic artery, with tPA administration continued with 0.75 to 1 mg/hour for 24 hours. Control angiography was performed the next day; if we did not observe adequate hepatic artery flow, tPA infusion continued for up to 72 hours; afterward, PTA was performed if needed, and a stent was placed for the hepatic artery.
Interventions for splenic artery steal syndrome
Splenic artery steal syndrome was confirmed with findings from a diagnostic arteriography from the celiac trunk that showed a patent hepatic artery but sluggish flow, delayed filling of intrahepatic arteries, and poor peripheral parenchymal perfusion with an early filling of an enlarged splenic artery.14,15 After confirmation of SASS, patients received a super-selective catheterization of the splenic artery with a 4F diagnostic catheter and a coil embolization from the proximal splenic artery (Figure 1). An angiogram after the embolization was performed to evaluate hepatic artery perfusion.
Interventions for hepatic vein and inferior vena cava complications
The right internal jugular vein was used to access for hepatic vein interventions. We inserted a 5F vascular sheath into the jugular vein and performed venography with a 5F pigtail catheter to define the HVOO. Angioplasty was performed over the 0.035-inch guidewire (Glidewire, Terumo) with balloons having diameters of 6 to 10 mm; if balloon angioplasty was insufficient, patients received stent placement. After endovascular interventions, hepatic venography and manometry were performed to determine the procedural success. For IVC interventions, the right femoral was accessed to achieve diagnostic venography with a 5F pigtail catheter. After the stenotic segment of the IVC was shown, balloon angioplasty was performed and a stent was placed if balloon angioplasty was insufficient (Figure 2).
Interventions for portal vein complications
Portal vein stenosis was managed with percutaneous transhepatic portal vein access by a biliary acoustic introducer system, and a 6F vascular sheath was inserted through the 0.035-inch guidewire. Afterward, the 0.018- to 0.035-inch guidewire with the 5F diagnostic catheter was passed through the stenotic segment of the portal vein, and spleno-portography was performed to determine the exact site of a stenotic segment of the portal vein. We then deployed an appropriately sized self-expandable stent (ev3, protage, Medtronic) at the stenotic segment of the portal vein (Figure 3). Balloon dilatation was performed if necessary. A control angiogram demonst-rated sufficient flow on the portal vein. Before the procedure was completed, we embolized the portal access track with the coils to prevent track bleeding.
During the study period, 43 of 240 LT recipients (17%) received endovascular treatment in the first week after LT because of vascular complications. All HAS and HAT events were encountered in living donor LT recipients. Seven patients with HAT received tPA (0.25-0.75 mg/h) infusion for 4 to 72 hours. Five patients were successfully treated with balloon angioplasty after continuous tPA infusion. For 1 of the 5 patients, arterial reocclusion was encountered the day after catheter-directed thrombolytic treatment, and a stent was inserted into the hepatic artery to maintain patency. This patient’s stent remained patent over follow-up. One patient had a HAS event 3 months after balloon angioplasty and received stenting with no further complications. The remaining 3 patients had no arterial complications during follow-up. One of the 7 patients with HAT received catheter-directed infusion of 2 mg of tPA and balloon angioplasty with unsatisfactory results; the patient then received stenting with good flow. Five days later, the stent was occluded, and tPA infusion was performed for 72 hours, with patency achieved without complications (Figure 4). Another patient with HAT received selective continuous intraarterial tPA infusion and balloon angioplasty, but this patient underwent surgical revision due to excessive arterial kinking. During follow-up, the patient received multiple arterial interventions due to reocclusion. Among 3 patients with HAS, 2 patients were treated with balloon angioplasty and 1 patient was treated with stenting because of insufficient arterial flow up. In 3 patients, the hepatic artery was patent during follow-up.
In addition to hepatic artery interventions, 2 of 10 patients received splenic artery embolization during the follow-up as a result of SASS. Four of the 10 patients with developed biliary complications, and those patients were HAT cases. Three patients had anastomotic stenosis and 1 had ischemic biliary stricture with biloma. Patients were treated with percutaneous anastomosis balloon dilatation and biliary drainage. During follow-up, 2 patients died. One of the patients had been administered an arterial revision and multiple arterial interventions, and the patient died as a result of multiple organ failure. The other patient died as a result of sepsis.
Twenty-seven of 240 LT recipients (11%) received a diagnosis of SASS angiographically. Patients with SASS consisted of 18 patients with living donor LT and 9 patients with deceased donor LT. After splenic artery embolization, control Doppler ultrasonog-raphy consistently showed normal hepatic artery flow, improved systolic amplitude, and increased diastolic flow in all treated patients. Resistance index values of the hepatic arteries showed a statistically significant decrease in posttreatment values compared with baseline measurements at SASS diagnosis (P < .001). Peak systolic velocity of the hepatic artery and portal vein maximal velocity improved significantly (P < .001) (Table 2). Local or systemic complications were not observed in any treated patient. Patients did not need any splenectomy during follow-up. Four patients with SASS had biliary complications on follow-up. Three had anastomotic site stenosis managed with a biliary drainage catheter and plastic stents. The other patient had an ischemic biliary complication with biloma. This patient died during follow-up as a result of sclerosing cholangitis.
Four patients (3 patients with HVOO and 1 patient with IVC stenosis) had venous complications in the first week after LT. All patients received primary balloon angioplasty. In 2 patients (1 with HVOO and 1 with IVC stenosis), stents were placed after insufficient results with balloon angioplasty, and stents were patent during the follow-up period. One patient with HVOO underwent stent placement 1 month after balloon angioplasty because of restenosis. The remaining 1 patient with HVOO and balloon angioplasty did not require an additional procedure during follow-up. Three biliary complications were observed during follow-up. Two were anastomotic stenosis, and one was biliary leakage treated with biliary drainage and plastic stent replacement. Four of the patient were still alive during the follow-up period.
Two patients with portal vein complications were encountered, and patients were treated with stent insertion for PVS. Both stents were patent during the follow-up period, with patients also alive over the follow-up period.
Despite advances in LT surgical techniques and medications, vascular complications are still one of the main issues determining liver graft function. Early detection of vascular sufficiency and early treatment could prevent graft loss and retransplant.16 In our review of the literature, endovascular procedures have been performed after a median or mean interval of 1 to 4 months after LT.1,2,11-13 This shows us that most centers are still reluctant to perform endovascular procedures during the first days after LT due to the risk of arterial dissection and hemorrhage.2 The reported complication rate was up to 23% after hepatic artery angioplasty procedures in LT recipients.5-6,17 There are a few studies that reported results of endovascular interventions in the first week after LT.18,19 Despite previous cases that have withheld from early endovascular interventions, we did not encounter arterial dissection or hemorrhagic comp-lications in our LT recipients. In our opinion, avoiding aggressive wire manipulations at the juxta-anastomotic site and using nontraumatic soft wires in arterial intervention are critical steps. In addition, the covered stent has been a safe and effective treatment tool after hepatic artery rupture.20
Careful selection of paired arteries with microsurgical technique, intraoperative Doppler ultrasonography, and postoperative thrombosis prophylaxis are significant in preventing occlusive and nonocclusive arterial complications.21-24 Despite the pre- and postoperative measures taken to avoid deterioration of graft arterial flow, arterial complications have been observed in 2% to 15% of patients.1-6,25-27 In our study, the arterial complication rate was similar at 4%. Seven of the 10 arterial events consisted of thrombosis occlusion, with HAT contributing to acute flow deterioration in the hepatic artery, which supplies the hepatic parenchyma and bile duct. An early incidence of HAT can result in high mortality, with a rate of 34.3% in a study of adults after LT.26 Hepatic artery stenosis may be an overlooked complication; HAS can cause persistent ischemic effects on the graft, leading to graft failure.1 In our study, the benefits of frequent Doppler examinations can allow determination of arterial disruption in the graft and pave the way for early endovascular interventions that can prevent graft loss. One of the valuable findings in our study showed that early detection and treatment can aid in preventing ischemic biliary damage that may present with ischemic cholangiopathy and sepsis, which can result in graft and patient loss.
Arterial vascularization methods include surgical revision, endovascular revascularization, and retransplant. Retransplant has been the gold standard treatment method, but timely retransplant may not be feasible in regions such as Asia due to organ shortages. In a systematic review, the success rate in adult LT recipients with HAT who are treated with surgical revascularization has been reported as 50.9%, and 32.3% of patients required retransplant after surgical revascularization.26 With these consideration, in our center, intra-arterial throm-bolysis is the first-choice therapy in early HAT after LT.
Various thrombolytic agents (urokinase, strep-tokinase, and tPA) have been used in hepatic artery complications, but there is no consensus on the use of thrombolytic agents, either temporarily or continuously. In our center, continuous tPA infusion (0.75-1 mg/h) is administered for 4 to 72 hours. If the patient has insufficient arterial graft flow due to residual thrombosis, tPA infusion is continued for 72 hours after stent replacement to overcome the residue thrombosis. The main concern in continuous thrombolytic therapy is hemorrhagic complications (incidence rate up to 20%).28 We monitored ACT levels and maintained ACT levels at between 140 and 180 to avoid hemorrhagic complications. We had only 1 local puncture site hematoma that presented with pseudoaneurysm, which was treated with ultrasonograph-guided thrombin injection. We did not have any life-threatening hemorrhage comp-lications in our study patients; in our opinion, tPA is a safe and effective treatment for patients with early HAT.
Splenic arterial steal syndrome is a well-recognized cause of graft failure when left untreated.29 The incidence of SASS varies from 0.6% to 8.4% as a posttransplant complication.14-15,30 Differences in SASS incidence may be due to being unrecognized diagnosis in some institutions and overdiagnosis in others. In our study, we reported an 11% incidence of SASS in the first week after LT. We suggest that this high incidence of SASS was related to close follow-up with ultrasonography in the early period posttransplant. At the slightest suspicion of arterial flow, the patients are treated by further evaluation with angiography.
In a review from Pinto and colleagues, SASS was reported to develop from the early period after LT to 5.5 years later.31 Another important aspect of our study was that the treatment of patients with SASS within the first week prevented complications that may lead to ischemic biliary damage and ultimately future graft loss. We encountered 4 biliary complications, with 3 nonischemic biliary comp-lications (anastomotic stenosis and biliary leakage), which were treated with biliary drainage. At the beginning of splenic artery embolization treatment, distal embolization was the preferred method but had high morbidity and mortality because of splenic abscess and sepsis complications.32 With gained experience, proximal splenic artery embolization became the preferred method, with significantly fewer complications. In our study, we did not encounter any complications in patients who underwent proximal embolization. Even in the early period after transplant, splenic artery embolization is a safe and effective treatment for SASS.
In our study cohort, we encountered 3 hepatic vein complications and 1 IVC stenosis in the first week post-LT. Venous complications can occur over a wide range of time, from the early posttransplant period to several months and years after LT.7,33 Early venous complications may occur as a result of several factors, including tight suture line, kinking of a redundant hepatic vein, caval compression from a large graft, or donor-recipient size discrepancy. Late venous complications (≥3 months post-LT) usually occur due to fibrosis of the anastomotic site and intimal hyperplasia.34 Treatment options for venous complications are angioplasty with or without stent placement, surgical reconstruction of the venous anastomosis, and retransplant. The existing literature has stated that early HVOO should be primarily treated with surgical revision; however, late venous complications should be treated with endovascular interventions because venous complications may cause liver and kidney function deterioration after a complicated surgical procedure.35-38 The main hesitation of an early endovascular intervention for venous complications is the rupture of the anastomotic site during revascularization. In our study cohort, no vein ruptures occurred during the revascularization. In our opinion, it is crucial to be aware of harsh manipulation with wire and catheter at the anastomotic site, and selecting an undersized balloon is the key to preventing complications.
In addition to arterial and vein complications, we encountered portal vein complications in 2 patients in the early period after LT. Portal vein stenosis usually occurs ≥1 month after LT and more frequently occurs in pediatric patients.39-42 As with early vascular interventions, the main concern for endovascular treatment for early PVS is anastomotic site rupture. Ko and colleagues43 suggested primary stent placement in PVC versus balloon angioplasty to prevent the risk of the anastomotic site rupture. However, Kim and colleagues40 treated PVS after LT with balloon angioplasty without rupture. In our 2 patients with PVS, we preferred primary stent insertion because of the possibility of rupture of the fresh anastomotic site. Sambommatsu and colleagues39 reported early (1 month after LT) portal vein complications in 14 patients (3 patients with PVS, 11 patients with PVT), with endovascular treatment having 100% success for early PVS and 91% success for PVT. In addition, their PVS cases were identified within 1 week post-LT, and they did not encounter portal vein complications after treatment during follow-up. We also did not observe portal vein complications during follow-up; unfortunately, 2 patients with PVS were lost. Early portal vein complications can be treated with surgical revision because these complications are usually caused by surgically correctable factors, including tension, twisting, kinking, or external compression ofthe portal vein. With the exclusion of surgically correctable cases, endovascular treatment is preferred. However, if PVS is left untreated, slow progression to portal vein occlusion can occur, which is more difficult to treat.44
The limitation of our study comes from the nature of its retrospective design. Nonetheless, this unique study included all types of vascular complications in the first week after LT. Despite advances in LT surgery and medications, vascular complications are still a significant cause of graft and patient loss in the early period after LT. With the consensus of the surgical team, intensive care, and interventional radiologists, the diagnosis and treatment of early vascular complications are essential in preventing graft and patient loss.
Volume : 20
Issue : 12
Pages : 1085 - 1093
DOI : 10.6002/ect.2022.0244
From the 1Department of Radiology, Istanbul Baskent University School of Medicine, Istanbul; the 2Department of Radiology and the 3Department of General Surgery, Ankara Baskent University School of Medicine, Ankara, Turkey
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Behlul Igus, Istanbul Baskent University School of Medicine, Department of Radiology, TR-34662 Istanbul, Turkey
Phone: +90 216 554 15 00 (1525)
Figure 1. Patient with Splenic Arterial Steal Syndrome after Liver Transplantation.
Figure 2. Patient With Inferior Vena Cava Stenosis After Liver Transplant
Figure 3. Patient With Portal Vein Stenosis After Liver Transplant
Table 2. Median Values at Time of Splenic Arterial Steal Syndrome Diagnosis and After Selective Arterial Embolization
Figure 4. Patient With Hepatic Artery Thrombosis After Liver Transplant