Objectives: Vascular complications after liver trans-plant can be lethal. High levels of suspicion and aggressive use of diagnostic tools may help with early diagnosis and treatment. Here, we share our experiences regarding this topic.
Materials and Methods: Adult and pediatric patients who had liver transplant between February 1997 and June 2018 in our clinic were included in the study. Patients were grouped according to age (pediatric patients were those under 18 years old), male versus female, indication for transplant, type of liver transplant, type of vascular complication, treatment, and survival after treatment. We analyzed the statistical incidence of vascular complications according to age, male versus female, and type of liver transplant.
Results: Our analyses included 607 liver transplant procedures, including 7 retransplants, with 349 (57.4%) from living donors and 258 (42.6%) from deceased donors. Of total patients, 539 were adults (89.8%) and 61 were children (10.2%). Vascular complications occurred in 25 patients (4.1%), with hepatic artery complications seen in 13 patients (2.1%) (10 adults [1.8%] and 3 children [4.9%]), portal vein com-plications seen in 9 patients (1.5%) (6 adults [1.1%] and 3 children [4.9%]), and hepatic vein complications seen in 3 patients (0.5%) (2 adults [0.36%] and 1 child [1.6%]). Rate of vascular complications was statistically higher in pediatric patients (11.4% vs 3.3%; P = .007) and higher but not statistically in recipients of livers from living donors (5.2% vs 2.7%; P = .19). Twelve patients (48.8%) were treated with endovascular approach, and 11 (0.44%) required surgical treatment. Two patients underwent immediate retransplant due to hepatic artery thrombosis.
Conclusions: Because vascular complications are the most severe complications after liver transplant, there must be close follow-up of vascular anastomoses, particularly early postoperatively, with radiologic methods. In cases of vascular complications, emergent treatment, including endovascular interventions, surgery, and retransplant, must be performed.
Key words : Endovascular intervention, Hepatic artery, Portal vein, Thrombectomy
Liver transplant (LT) is a lifesaving treatment that is mainly used for end-stage liver disease, acute liver failure, and in selected liver cancer patients.1-4 Currently, 1-year survival in LT is around 80% to 90% due to improvements in surgical technique, anesthesia, and postoperative care and organ preservation as well as new immunosuppressive medication options.5,6 These improvements have led to 3-year and 5-year survival rates of 80% and 74%.7 However, with increased survival, the number of reported cases of both early- and late-stage complications has increased.
Occlusive vascular complications, including thrombosis and stenosis, are serious complications, resulting in mortality and graft loss.8,9 The rate of vascular complications after LT has been reported to range from 7% to 15%; however, the rate has been as high as 25% to 30% in living-donor LT (LDLT), pediatric LT, and split deceased-donor LT (DDLT).10-14 Vascular complications may include hepatic artery, portal vein, and hepatic vein problems. In particular, early postoperative hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) can result in graft dysfunction, graft failure, and mortality due to decreased vascular supply in the graft.9,15 Therefore, early diagnosis and treatment are vital in terms of graft viability and patient survival.11,16-21 Options of treatment include endo-vascular interventions like percutaneous trans-luminal angioplasty with stent (PTAS) or without stent (PTA), surgical repair (thrombectomy, resection, and reanastomosis), and retransplant. In this study, we present both adult and pediatric LT patients, operated in our clinic, their vascular complications, and the treatment choices and results.
Materials and Methods
Our study included adult and pediatric patients who had liver transplant procedures between February 1997 and June 2018. Patient data had been collected prospectively, with data analysis made retro-spectively. Patients were grouped according to age, male versus female, indication for LT, type of LT, type of vascular complication, treatment, and survival after treatment. Patients under 18 years old were grouped as pediatric patients.
Every transplant recipient received 100 IU/kg/day of intravenous heparin, to keep activated pro-tromboplastin time 2 times higher than the upper limit of normal. For cases of heparin-induced thrombocytopenia, we used low-molecular-weight heparin. After discharge, patients were prescribed acetylsalicylic acid with doses according to their weight. Intraoperatively, we performed Doppler ultrasonography to check whether the anastomoses were intact. After transplant, patients received Doppler ultrasonography daily for 10 days, with selected patients receiving multiple Doppler scans per day. Ten days after transplant, anastomoses were checked weekly by Doppler ultrasonography. In cases of possible stenosis or thrombosis shown by Doppler scans, results were confirmed with com-puted tomography angiography (CTA) or magnetic resonance angiography.
Cases of hepatic artery thrombosis diagnosed in the first month after LT were grouped as “early complications,” and cases after the first month were grouped as “late complications.” We analyzed the statistical incidence of vascular complications among age groups, male versus female, and type of liver transplant.
All statistical analyses were performed using IBM SPSS Statistics software version 18.0 (IBM, Chicago, IL, USA). All data are shown as means ± standard deviation. P < .05 was considered statistically significant.
From February 1997 to June 2018, our center performed liver transplant procedures in 600 patients, including 7 retransplant procedures: 349 (57.4%) were from living donors and 258 (42.6%) were from deceased donors. In total, we performed 607 LT procedures. Of total patients, 539 (89.8%) were adults, which included 153 female patients (28.3%) and 386 male patients (71.7%). Sixty-one LT recipients (10.1%) were pediatric patients, which included 38 male patients (62.3%) and 23 female patients (37.7%).
Of 539 adult and 61 pediatric LT recipients, 18 (3.3%) and 7 (11.4%), respectively, had vascular complications in the perioperative period. Eleven patients (1.8%) were diagnosed with HAT, and 2 patients (0.3%) were diagnosed with hepatic artery stenosis (HAS). Among adult patients, 8 (1.4%) developed HAT (5 early and 2 late); among pediatric patients, 3 (4.9%) developed HAT (Figure 1). The 2 patients who developed HAS were both adults. Portal vein thrombosis developed in 3 patients (0.5%) in the adult group and in 3 patients (4.9%) in the pediatric group.
Two adult LT recipients (0.3%) developed portal vein stenosis (PVS). None of the patients who developed PVT or PVS had preoperative PVT, and none had interposition graft used intraoperatively.
Hepatic vein thrombosis (HVT) developed in only 1 adult patient (0.2%), whereas hepatic vein stenosis developed in 1 adult (0.2%) and 1 (1.6%) pediatric patient.
Among 18 adult LT recipients with vascular complications, 12 were men (66.6%) and 6 were women (33.3%). Thirteen (72.2%) of these patients had LDLT, and 5 (27.7%) had DDLT. Of the 18 adult patients who developed vascular complications, 14 (77.7%) died.
In 7 pediatric LT recipients with vascular com-plications, 3 were boys (4.9%) and 4 were girls (6.5%). Five (8.2%) of these patients had LDLT, and 2 (3.2%) had DDLT (1 had split segment 2+3, 1 had whole liver transplant). Of 7 patients with vascular complications, 2 patients (28.5%) had LT due to indication of cirrhosis secondary to Wilson disease. Three of the 7 patients with vascular complications (42.8%) died post-operatively. Data on vascular complications in pediatric and adult LT recipients are shown in Table 1.
When we compared the incidence of vascular complications, the pediatric group (11.4%) had significantly more complications than the adult group (3.3%) (P = .007). The incidence of vascular complication in those who underwent LDLT was 5.2%, whereas the incidence in those who had DDLT was 2.7% (not significantly different; P = .19). Similarly, we observed no significant differences in incidence in male versus female patients (P = .37).
Among 8 patients who developed early HAT (5 in LDLT [2 adults/3 children] and 3 in DDLT), 2 patients were treated with PTA, 4 were treated with emergency surgery, and 2 were treated with retransplant. During PTA, anastomosis rupture occurred in 1 patient who was treated with emergency surgery. Another patient treated with PTA developed rethrombosis, and 2 patients died due to irreversible graft ischemia. Four patients who developed HAT were not successfully treated with revascularization techniques and died from graft dysfunction. Successful treatment was shown in the 2 retransplant patients, who showed no further complications or problems at follow-up.
All 3 patients with late HAT were adults (2 with DDLT, 1 with LDLT); these patients were diagnosed at 4 months, 5 months, and 6 years posttransplant. One patient had history of graft rejection before developing HAT. Three patients developed biliary stricture and cholangitis attacks secondary to biliary ischemia and multiple pericholangitic abscesses. In these patients, we performed percutaneous trans-hepatic biliary drainage. However, all 3 patients died due to recurrent cholangitis attacks resulting in biliary sepsis. Two adult patients (LDLT) who developed HAS at postoperative days 6 and 10 were successfully treated with PTAS (Figure 2).
Six patients who developed PVT were treated with surgical revascularization. Two pediatric patients were treated successfully with surgical thrombectomy. However, the other 4 patients died because of early graft necrosis and dysfunction after unsuccessful treatment. Three patients with PVS were treated by interventional radiology with PTAS, and the vein was successfully recanalized (Figure 3). In 1 of these 3 patients, a second endovascular intervention was performed due to restenosis. The 2 patients (1 adult and 1 child, both with LDLT) who developed HVS were treated with PTAS (Figure 4). One of these patients developed restenosis, and we performed a second endovascular intervention; no further complications were shown in follow-up. One patient who developed HVT was treated with surgical revascularization unsuccessfully, and the patient died. Types of vascular com-plications, treatment ap-proaches, and outcomes are summarized in Table 2.
Vascular complications after LT can result in increased morbidity and mortality. A hypercoagulable state after LT increases the risk of life-threatening occlusive vascular complications. Transplant centers suggest different strategies to prevent hypercoagulability after LT.22 In our clinic, all LT patients receive heparin or low-molecular-weight heparin early posttransplant; after discharge, we stop heparin use and prescribe oral acetylsalicylic acid.
The state of vascular anastomoses early after transplant should be closely followed radiologically. For this purpose, the first suggested method is Doppler ultrasonography.23,24 Doppler ultrasono-graphy is a highly sensitive and efficient method for examination of vascular complications.25 Although clinical signs and symptoms and laboratory results are predictive in the diagnosis of vascular com-plications, radiologic tests are vital in diagnosis because they show actual vascular flow. However, in case of possible vascular pathology, more sensitive and specific methods, including CTA or magnetic resonance angiography, are recommended.26,27 In our clinic, when possible vascular pathology is shown via Doppler scans, we use CTA routinely.
As shown in our study, minor and in some cases multiple vascular structures are more common in LDLT than in DDLT.16,28 Among 257 patients with DDLT, 7 patients (2.7%) developed vascular com-plications; in 343 LDLT patients, 17 (4.7%) developed complications (P = .19). Therefore, it is necessary to perform more complicated reconstructions in these cases.
Liver transplant in pediatric recipients also has increased risk of vascular complications, owing to smaller vascular diameters.9,29 These results correlate with our results in which pediatric patients had significantly more vascular complications than adult patients (11.4% vs 3.3%; P = .007).
Male sex has also been shown to be a risk factor for vascular complications, particularly for portal vein complications.30 In our study, we did not find any statistical difference between males and females in terms of vascular complications (P = .37).
Although overall rate of vascular complications after LT has been shown to be 7% to 30%,10-19 in our sample, the rate was 4.1%. We assume that our lower incidence was because of relatively fewer pediatric patients (10.1%), who require more complex vascular reconstruction. Regarding type of vascular pathology, the literature has reported 4.8% to 16.6% among portal vein, 1.2% to 12.3% among hepatic vein, and 1.2% overall complication rate.10,13,14 The incidence of arterial complications also varies, with rates ranging from 3% to 9%.31-33 Arterial com-plications are reported as more common than venous complications after LT, causing more graft loss and mortality.6,10 Many factors have been defined as risk factors for hepatic artery complications.34-36
Early HAT can result in graft loss and mortality if not immediately treated; in late HAT, prognosis has become significantly better thanks to collateral vessels.13,37 In late HAT cases, recurrent cholangitis attacks and pericholangitic abscesses as well as biliary sepsis resulting from biliary leakage are more common due to progressive biliary ischemia.38-40 Similar to other vascular complications, arterial complications can be treated with endovascular interventions, surgical revascularization, or retransplant.15,40 However, for cases of irreversible graft injury, retransplant is the only option.9 In most HAT cases, the only treatment option may depend on organ supply.35 Traditionally, surgical revas-cularization techniques are the first line of treatment with arterial complications. However, interventional techniques (PTA/PTAS) have become the treatment of choice due to their success rate.35,41-44 In early HAT cases, endovascular techniques are not preferred due to risk of rupture.45 Boyvat and associates reported that graft-covered stents may be placed safely and effectively in early posttransplant cases.46
In our study, incidence of arterial complications was 2.1% (13/600), which is lower than shown in the literature. Similar to the literature, arterial comp-lications were the major component of vascular complications in our sample (50%). In the literature, HAT rate ranges from 0.8% to 9.3%; our sample showed a comparable HAT rate of 1.8%. Of 11 HAT cases, 8 patients were classified as early and 3 were classified as late complications. In early HAT cases, 5 (0.9%) were adults and 3 (4.9%) were children. In comparison, Bekker and associates reported an early HAT incidence of 2.9%, with incidence in pediatric patients of 8.3%.33 In 2 of the patients with HAT, we tried endovascular intervention, with 1 patient having anastomotic rupture and emergency surgical repair and the other developing rethrombosis after PTA; both of these patients died. Four patients received unsuccessful surgical revascularization, and the patients died from irreversible graft dysfunction. Two patients with HAT were treated with retransplant and were discharged without any complications and no further problems at follow-up. Two patients who developed HAS were treated successfully with PTAS. In total, 69% of patients who developed hepatic artery complications died. The main reason for the high mortality was an inability to perform retransplant due to lack of graft supply. The only valid treatment after irreversible graft ischemia is retransplant.
Our incidence of portal vein complications was 1.5%, which is similar to the literature.47,48 Many factors have been defined as risk factors for portal vein complications.15,30 In our study, 6 patients (1%) developed PVT and 2 developed PVS. Three of these 6 patients were children, and 1 of these had portosystemic shunt before surgery. In 1 of the 3 adult patients with PVT, we observed slow blood flow during intraoperative ultrasonography, and we performed splenic artery ligation. In the remaining 2 patients, 1 had LT due to Budd-Chiari syndrome and the other had LT due to hepatocellular carcinoma, which were considered risk factors.
Endovascular interventions and thrombolytic agents are successful options in treatment of PVT; however, these cases are quite rare. Surgical throm-bectomy and reanastomosis are better known as first-line treatment in PVT.8 In our study, all 6 patients with PVT had emergency surgical revascularization, which was unsuccessful for 4 patients. The other 2 patients who received thrombectomy had no additional problems at follow-up.
In cases with PVS, endovascular interventions (PTA/PTAS) can result in high success rates.45,46 In cases when endovascular interventions are not suitable, surgical treatment should include resection of stenotic segment and reanastomosis with or without vascular graft. In our study, 3 patients with PVS were treated with PTAS, with 1 patient requiring endovascular revision due to restenosis. In our sample, we had 3 hepatic vein complications (2 HVS and 1 HVT). Two patients with HVS were treated with PTAS, with 1 patient requiring endovascular revision due to restenosis. One patient with HVT was treated with surgical thrombectomy, but the patient died due to graft dysfunction.
Vascular complications after LT are significant causes of morbidity and mortality. During the early postoperative period, vascular anastomosis must be closely followed with radiologic methods. In cases of vascular complications, emergent treatment options, including endovascular interventions, surgery, and retransplant, must be considered.
DOI : 10.6002/ect.2018.0240
From the 1Department of General Surgery, Hepatopancreaticobiliary Surgery and
Liver Transplantation Unit, the 2Department of Radiology, Division of
Interventional Radiology, Dokuz Eylul University Faculty of Medicine, Narlıdere,
Izmir, Turkey; and the 3Department of General Surgery, Hepatopancreaticobiliary
Surgery and Liver Transplantation Unit, Guven Hospital Ankara, Turkey
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare. The authors thank Dr. Aylin Bacakoglu for valuable contributions.
Corresponding author: Tufan Egeli, Dokuz Eylul University School of Medicine Department of General Surgery, Hepatopancreaticobiliary Surgery and Liver Transplantation Unit, Narlıdere, Izmir, Turkey
Phone: +90 232 412 2901
Figure 1. Coronal Multiplanar Reformat Computed Tomography Angiography Image
Figure 2. Hepatic Angiogram of Transplanted Liver
Figure 3. Portal Venogram of Transplanted Liver
Figure 4. Hepatic Vein Stenosis
Table 1. Characteristics of Patients and Vascular Complications Among Adult and Pediatric Liver Transplant Recipients
Table 2. Type of Vascular Complication, Treatment Approach, and Outcome