Objectives: Vascular problems such as thrombosis and stenosis of the hepatic artery, portal vein, and hepatic vein are serious complications after living-donor liver transplant and can cause increased morbidity, graft loss, and patient death. The aim of this study was to assess the incidence, treatment, and outcome of recipient vascular complications after living-donor liver transplant in a single Egyptian center.

Materials and Methods: Between November 2006 and March 2014, we performed 226 living-donor liver transplants for 225 patients at Dar Al Fouad Hospital in 6th of October City in Egypt. Review of all patients with vascular complications was performed.

Results: In 20 of 225 recipients (8.9%), there were vascular complications that occurred from day 0 to 14 (mean, 5.6 ± 3.4 d). Complications included isolated hepatic artery thrombosis in 7 patients (35%), isolated portal vein thrombosis in 6 patients (30%), isolated hepatic vein stenosis in 3 patients (15%), and isolated hepatic artery stenosis in 1 patient (5%). Combined portal vein thrombosis and hepatic artery thrombosis occurred in 2 patients (10%), and combined portal vein thrombosis and hepatic vein stenosis occurred in 1 patient (5%). Complications were identified with duplex ultra­sonography and confirmed with computed tomographic angiography and direct angiography when needed. Multidisciplinary treatment included percutaneous transarterial or transvenous throm­bolysis with or without balloon dilation and stenting, open surgical exploration with throm­bectomy, vascular revision, or retransplant. There were no intraoperative deaths, but mortality occurred in 15 of 20 patients (75%). Survival ranged from 6 days to 70 months. Preoperative portal vein thrombosis was observed in 3 of 7 patients (43%) who had postoperative portal vein thrombosis.

Conclusions: Major vascular complications in living-donor liver transplant recipients have poor outcome despite early detection and prompt multi­disciplinary intervention. Preoperative recipient portal vein thrombosis is a risk factor for post­operative portal vein thrombosis.

Key words : Hepatic artery stenosis, Hepatic artery thrombosis, Hepatic vein stenosis, Portal vein thrombosis

Introduction

Vascular complications after living-donor liver transplant are serious problems that frequently result in graft loss and patient death.¹ Despite marked improvements in vascular techniques during the past several decades, the overall incidence of vascular complications in adults is 8% in studies of deceased-donor liver transplant²; the incidence is 10% after living-donor liver transplant because of the smaller vessels, insufficient vessel length for reconstruction, and greater risk of a twist of the vascular pedicle.³ Close surveillance of all vascular anastomoses using duplex ultrasonography facilitates early detection and treatment of these complications before irreversible graft failure occurs. Treatment options usually include percutaneous thrombolysis, percutaneous angioplasty, surgical revascularization, retransplant, or, less commonly, a nonoperative approach.¹

The aim of this study was to assess the incidence, treatment, and outcome of vascular complications in recipients after living-donor liver transplant at a single Egyptian center (Dar Al Fouad Hospital, 6th of October City, Egypt).

Materials and Methods

Subjects
The charts of recipients who had living-donor liver transplant performed at Dar Al Fouad Hospital between November 2006 and March 2014 and who developed vascular complications were reviewed retrospectively. Analysis was performed of recipient demographics, preoperative imaging, vascular complications (type, time of occurrence, and treatment), and outcome. The study was approved by the ethics committee before this work began, and the protocols conformed with the ethical guidelines of the 1975 Declaration of Helsinki. Written informed consent was obtained from patients or their guardians including approval of the treatment protocol and anonymous use of data for research purposes.

All transplants were performed by the same surgical team. All grafts were right liver lobe grafts without the middle hepatic vein from a living donor. Hepatic vein anastomosis was performed end-to-side with continuous 5-0 polypropylene suture with 3× loupe magnification. Portal vein anastomosis was performed end-to-end with continuous 6-0 polypropylene suture, also with 3× loupe magnification. Hepatic artery anastomosis was done end-to-end with interrupted 8-0 polypropylene sutures using a microscope with 4× to 8× magnification, depending on artery size. Duplex ultrasonography examination was performed intraoperatively immediately after finishing the anastomoses to ensure vascular patency and was repeated daily within the first 3 weeks after transplant. All patients were transferred to the intensive care unit for the first 5 days after surgery and transferred to the ward for the remainder of the first 3 weeks unless there was a major complication. Graft function was monitored by detailed daily biochemical tests. All patients received heparin infusion during the first 5 days; subsequently, they received low molecular weight heparin and aspirin until the end of the first 3 weeks, and aspirin for 6 months.

The diagnosis of vascular complications was established by a minimum of 2 imaging tests and/or surgical confirmation. A multidisciplinary team including microsurgeons, transplant surgeons, interventional radiologists, and hepatologists decided on the treatment protocol.

Technique of intra-arterial thrombolysis
Diagnostic arteriography was performed with standard catheter techniques using right femoral artery access with selective catheterization of the celiac trunk using 5 French Cobra or Simon catheters. After hepatic artery thrombosis (HAT) was confirmed, a microcatheter with side holes was manipulated into the thrombus. Thrombolysis was performed with a bolus dose of streptokinase (150 000 U). If the artery did not recanalize, continuous infusion (100 000 U/h) was performed for maximum 12 hours. If the angiogram after recanalization showed an underlying stricture, balloon angioplasty and stent placement were performed. The endovascular interventions were monitored using duplex ultrasonography to ensure good arterial flow in the graft during the procedures. During continuous infusion, duplex ultrasonography was performed every 2 hours. The infusion was stopped when the duplex scan showed arterial flow in the hepatic artery at the graft hilum and intrahepatic branches, and this was followed by confirmatory angiography. Follow-up was per-formed using daily duplex ultrasonography (every 12 hours for the first 3 days; after 3 days, once daily until hospital discharge). Successful intra-arterial thrombolysis was defined as resolution of the thrombus with delineation of the intrahepatic branches.

Technique of hepatic vein venography and venoplasty
The right internal jugular vein was used for vascular access. Pre- and postanastomotic hepatic venous pressures and pull-through pressures were measured. If a major anastomotic stenosis was identified, then a stiff 0.035-inch guide wire was passed through the stenotic segment, and this was followed by dilation with a balloon (venoplasty). An appropriately sized metallic stent was used in cases with failure of the balloon waist to expand during inflation, persistent pressure gradient (> 5 mm Hg) during balloon dilation, and/or recurrent stenosis with persistent pressure gradient after dilation. Patients received systemic anticoagulation with heparin sodium to maintain partial thromboplastin time 1.5-fold greater than normal level immediately after the procedure.

Results

Patients
There were 226 adult living-donor liver transplant procedures performed for 225 adult recipients between November 2006 and March 2014. Vascular complications developed in 20 patients (8.9%) (Table 1). There were 2 females (10%) and 18 males (90%). The preoperative diagnosis was posthepatitis C liver decompensation in 17 patients (85%) and hepatocellular carcinoma in 3 patients (15%). Their age range was 26 to 68 years, with mean age 49.6 ± 9.4 years. Preoperative triphasic computed tomography (CT) of the abdomen showed portal vein thrombosis (PVT) in 3 of the 7 patients who developed ostoperative PVT. There were 2 patients who had grade II PVT and 1 patient who had grade III PVT.4 Portal vein thrombectomy was performed in these 3 patients before hepatic graft implantation (Figure 1). The correlation between preoperative PVT and the development of postoperative PVT was statistically significant (P = .021) using the McNemar test.

Incidence
Vascular complications were identified by duplex ultrasonography and confirmed by hepatic CT angiography and percutaneous transarterial angiography when diagnosis was not definite. In the 20 recipients who had vascular complications, isolated HAT occurred in 7 patients (35%), isolated PVT in 6 patients (30%), isolated hepatic vein stenosis (HVS) in 3 patients (15%), and isolated hepatic artery stenosis (HAS) in 1 patient (5%). Multiple com­plications occurred in 3 patients: combined PVT and HAT in 2 patients (10%) and combined PVT and HVS in 1 patient (5%) (Table 2). Time of occurrence of vascular complications ranged from 0 to 14 days (mean, 5.6 ± 3.4 d) (Table 3).

Treatment
Isolated HAT was treated by percutaneous trans­arterial thrombolysis alone in 2 patients (Figure 2) with additional balloon dilation and stenting in 2 other patients. The reason for the stenting was the appearance of an anastomotic stricture in 1 patient (Figure 3) and a kink in the other patient after the thrombus had resolved. The stricture was caused by > 2:1 size mismatch between the recipient and graft arteries. Another case occurred on day 1 and was treated with surgical exploration and thrombectomy, but HAT recurred and was treated with percutaneous transarterial thrombolytic infusion. In 1 patient, HAT developed during a severe rejection episode with graft failure and was treated with retransplant, but HAT recurred; the patient received percutaneous transarterial thrombolytic infusion unsuccessfully and died because of biliary problems. Another patient had graft artery intimal dissection intraoperatively and the arterial anastomosis was repeated 6 times, finally with a saphenous vein graft, but there still was no flow because of intrahepatic arterial dissection. The patient with isolated HAS was treated with percutaneous transfemoral balloon angioplasty and stent.

The 6 patients with isolated PVT were treated with surgical exploration and thrombectomy through a small transverse venotomy in the accessible main portal vein. Care was taken not to disrupt the arterial and biliary anastomoses which were anterior to the vein. Fogarty balloon catheters were used to extract intrahepatic thrombi proximally and distally. However, some segmental branches remained occluded (Figure 4), and thrombolytic therapy was considered life-threatening because of the abnormal coagulation profile.

In the 3 patients who had isolated HVS, 1 patient had a redundant hepatic vein anastomosis inverted into the vein lumen and underwent percutaneous transjugular hepatic vein stent placement (Figure 5). The other 2 patients had received middle hepatic vein dominant grafts with small right hepatic veins and a segment 8 vein that was not reconstructed, which caused congestion, and they were treated non­operatively.

There were 2 patients who had combined PVT and HAT. Surgical thrombectomy was done for PVT in both patients, and HAT was treated with balloon angioplasty and stent in 1 patient and saphenous vein interposition graft in the other patient. The patient who had combined PVT and HVS was treated nonoperatively (Table 4).

Prognosis
Survival ranged from 6 days (0.2 mo) to 70 months; least survival was observed in patients who had PVT and longest survival in patients who had HAT (Table 5). Survival was 70% at 1 mo, 25% at 6 mo, 25% at 1 y, and 10% at 5 y. Death occurred in 15 of 20 patients (75%) because of different causes (Table 6). The most common cause of death was graft failure in 8 patients (40%). There were 5 patients who were considered censored because they were lost to follow-up during the study.

Discussion

Vascular complications are a major cause of morbidity and mortality after liver transplant. The complication HAT is a serious problem, with a reported incidence 3% to 5% in adults and 8% to 12% in pediatric recipients.^5,6 The complication HAT usually occurs early within the first 2 weeks after transplant and is associated with major graft loss and mortality.² In our series, the overall incidence of HAT was 4% of 226 living-donor liver transplant procedures performed. Potential risk factors for HAT have been identified in many studies and may be surgical (technical) or nonsurgical.⁷ We encountered an underlying anastomotic stricture in 1 patient who developed HAT (Figure 3). The arterial anatomy of both recipient and donor graft can affect the incidence of HAT. Smaller arteries are associated with higher incidence of HAT, evidenced by the higher rate in pediatrics.⁸ A common problem is the discrepancy in size between the graft and recipient arteries. We encountered a > 2:1 size mismatch between the recipient and graft arteries. Different techniques have been described for an anastomosis in such cases, such as spatulation of the smaller artery.⁷ In our series, 1 patient developed HAT because of a major kink. Before starting the anastomosis, we presently try to estimate where the final arterial position will be located after removal of the abdominal retractors and descent of the diaphragm and liver caudally, and we excise any excess artery. Intimal dissection is another risk factor that is problematic especially in the graft artery where the flap is located along the direction of blood flow, but some recipient artery dissections may be amenable to repair by tacking the intima to the separated media/adventitia while placing the interrupted anastomotic stitches.

After declamping the antegrade blood flow will coapt the layers. We encountered dissection on the graft side in 1 patient who developed HAT intraoperatively and the anastomosis was repeated 6 times, finally using a saphenous vein graft interposition because of the short graft artery after repeated attempts, but there was no flow after all attempts. This is a catastrophic event and we do not insert a cannula into the artery during back table perfusion to prevent this complication. Nonsurgical potential risk factors include hypercoagulable disorders (thrombophilias) in the recipient and donor, cytomegalovirus mismatch, ABO incom­patibility, and the arterial reperfusion time.⁷ Prolonged operative times also are suggested as a risk factor. Another important risk factor is acute rejection episodes, which increase the capillary bed resistance and impede arterial flow.^5,8-10 We encountered 1 patient who developed HAT because of acute rejection on postoperative day 14, for which retransplant was done because of graft failure, but HAT recurred because of recurrence of acute rejection after retransplant. Interrupted sutures are associated with fewer hepatic arterial complications.¹¹ The use of magnification microscopes with continuous zoom and high magnification loupes reduces the incidence.¹² The complication HAS is a risk factor for HAT and should be corrected when detected during routine duplex ultrasonography surveillance.⁷

Complications related to the portal vein are less common than those of the hepatic artery but are associated with high graft loss incidence.¹³ In our series, we observed that preoperative PVT significantly correlated with posttransplant PVT (P = .021). Our protocol in patients who have preoperative PVT and who undergo thrombectomy during the transplant before portal anastomosis is to administer heparin infusion for 5 days, followed by low molecular weight heparin for three weeks and warfarin for 6 months. The 3 patients who underwent thrombectomy developed PVT despite being on the protocol; therefore, we are considering routinely inserting an inferior mesenteric vein catheter during transplant in these patients that can be used for anticoagulation or thrombolysis if PVT develops. Prompt detection and aggressive surgical treatment are required to reduce mortality and graft loss.¹⁴

The complication HVS should be suspected whenever there is unexplained increasing ascites or graft dysfunction. Percutaneous transjugular angioplasty usually is an effective method to relieve hepatic vein or inferior vena cava stenosis.^15,16 In 1 of our patients, there was a redundant hepatic vein internally inverted anastomosis that was treated successfully with a stent. To avoid HVS, we recommend performing a large venotomy in the inferior vena cava to anastomose to the graft right hepatic vein. We do not use anterior patches. Furthermore, we recommend reconstruction of segment 8 vein if the right hepatic vein is small, even if the graft is of adequate size, to avoid congestion.

Reported survival rates for recipients with vascular complications is 88.9% at 1 mo, 66.7% at 6 mo, and 33.3% at 12 mo.¹⁷ In our series, survival rate was 70% at 1 mo, 25% at 6 mo, 25% at 12 mo, and 10% at 5 y; least survival was observed in patients who had PVT and longest survival was in patients who had HAT.

In conclusion, major vascular complications in living-donor liver transplant recipients have poor outcome with major graft and patient loss. Detailed preoperative preparation, refining surgical technique and decision making, identifying risk factors, early diagnosis with routine surveillance, and prompt multidisciplinary treatment are needed to reduce the incidence of vascular complications and associated graft loss and patient mortality.

References:

1. Khalaf H. Vascular complications after deceased and living donor liver transplantation: a single-center experience. Transplant Proc. 2010;42(3):865-870.
2. Duffy JP, Hong JC, Farmer DG, et al. Vascular complications of orthotopic liver transplantation: experience in more than 4,200 patients. J Am Coll Surg. 2009;208(5):896-903.
3. Someda H, Moriyasu F, Fujimoto M, et al. Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US. J Hepatol. 1995;22(6):623-632.
4. Lladó L, Fabregat J, Castellote J, et al. Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality. Clin Transplant. 2007;21(6):716-721.
5. Bekker J, Ploem S, de Jong KP. Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors. Am J Transplant. 2009;9(4):746-757.
6. Lisman T, Porte RJ. Hepatic artery thrombosis after liver transplantation: more than just a surgical complication? Transpl Int. 2009;22(2):162-164.
7. Abdelaziz O, Hosny K, Amin A, Emadeldin S, Uemoto S, Mostafa M. Endovascular management of early hepatic artery thrombosis after living donor liver transplantation. Transpl Int. 2012;25(8):847-856.
8. Proposito D, Loinaz Segurola C, Garcia Garcìa I, et al. Assessment of risk factors in the incidence of hepatic artery thrombosis in a consecutive series of 687 liver transplantations [in Italian]. Ann Ital Chir. 2001;72(2):187-205.
9. Ayala R, Martínez-López J, Cedena T, et al. Recipient and donor thrombophilia and the risk of portal venous thrombosis and hepatic artery thrombosis in liver recipients. BMC Gastroenterol. 2001;11: 130.
10. Warner P, Fusai G, Glantzounis GK, et al. Risk factors associated with early hepatic artery thrombosis after orthotopic liver transplantation - univariable and multivariable analysis. Transpl Int. 2011;24(4):401-408.
11. Coelho GR, Leitao AS Jr, Cavalcante FP, et al. Continuous versus interrupted suture for hepatic artery anastomosis in liver transplantation: differences in the incidence of hepatic artery thrombosis. Transplant Proc. 2008;40(10):3545-3547.
12. Amin AA, Kamel R, Hatata Y,et al. Crucial issues of hepatic artery reconstruction in living donor liver transplantation: our experience with 133 cases at Dar El-Fouad Hospital, Egypt. J Reconstr Microsurg. 2009;25(5):307-312.
13. Mitchell A, John PR, Mayer DA, Mirza DF, Buckels JA, De Ville De Goyet J. Improved technique of portal vein reconstruction in pediatric liver transplant recipients with portal vein hypoplasia. Transplantation. 2002;73(8):1244-1247.
14. Corno V, Torri E, Bertani A, et al. Early portal vein thrombosis after pediatric split liver transplantation with left lateral segment graft. Transplant Proc. 2005;37(2):1141-1142.
15. Kawano Y, Akimaru K, Taniai N, et al. Successful transjugular balloon dilatation of the hepatic vein stenosis causing hypoalbuminemia after pediatric living-donor liver transplantation. Hepatogastroenterology. 2007;54(78):1821-1824.
16. Miraglia R, Luca A, Marrone G, et al. Percutaneous transhepatic venous angioplasty in a two-yr-old patient with hepatic vein stenosis after partial liver transplantation. Pediatr Transplant. 2007;11 (2):222-224.
17. Steinbrück K, Enne M, Fernandes R, et al. Vascular complications after living donor liver transplantation: a Brazilian, single-center experience. Transplant Proc. 2011;43(1):196-198.