Vascular complications following liver transplantation: A literature review of advances in 2015

Table 1 Vascular complications following orthotopic liver transplantation

Type	Delay (incidence)	Clinical presentation	Diagnosis	Treatment
Arterial complications
HAT incidence: 3.5%	Early HAT (2.9%)	Abnormal transaminase	DUS	Emergent revascularization
		Fever	ce-MDCT	by endovascular intervention
		Biliary complications	Angiography	or surgical revascularization
		Graft failure		or rLT
		Coagulopathy
	Late HAT (2.2%)	Asymptomatic
		Fever
		Abnormal transaminase
		Bile leak
		Hepatic abscess
		Cholangitis
HAS incidence: 2%-13%	Early HAS	Graft failure	DUS	Endovascular intervention
		Biliary complications	ce-MDCT	or surgical revascularization
			Angiography
	Late HAS	Asymptomatic	DUS	Endovascular intervention
		Fever	ce-MDCT	or surgical revascularization
		Abnormal liver function	Angiography
HAP incidence: 2.5%		Asymptomatic	DUS	Endovascular intervention
		Abdominal pain	ce-MDCT	or surgical resection and revascularization
		Fever	Angiography
HAR incidence: 0.64%		Gastrointestinal bleeding	None in emergency	Emergent surgical hemostasis
		Massive bleeding through abdominal drains		and surgical repair
		Hemorrhagic shock
Portal vein complications
PVT incidence: < 3%	Early	Abnormal transaminase	DUS	rLT
		Graf dysfunction	ce-MDCT	or surgical repair
		Multi-organe failure	(portal phase)	or endovascular interventions
		Variceal bleeding	Portography
	Late	Ascite	DUS	Curative anticoagulant therapy
		Portal vein hypertension	ce-MDCT
		Splenomegaly	(portal phase)
		Variceal bleeding	Portography
PVS incidence: 2%-3%	Early	Asymptomatic	DUS	Endovascular interventions
		Portal vein hypertension	ce-MDCT
		Abnormal transaminase	(portal phase)
			Portography
	Late	Asymptomatic	DUS	Anticoagulant therapy
		Ascite	ce-MDCT	and/or
		Abnormal liver test function	(portal phase)	Endovascular interventions
			Portography
Caval anastomosis complications
Caval resection and end-to-end	Early	Acute Budd-Chiari syndrome	DUS	Endovascular intervention
cavo-caval anastomosis		Graf failure	ce-MDCT	or surgical repair
		Intestinal congestion	Cavography	or rLT
		Renal dysfunction
		Lower limb edema
	Late	Moderate Budd-Chiari syndrome	DUS	Endovascular intervention
		Ascite	ce-MDCT
			Cavography
Piggy-back	Early	Acute Budd Chiari	DUS	Surgical repair
		Graf failure	ce-MDCT	or rLT
		Intestinal congestion	Cavography
		Renal dysfunction
		Lower extremity edema
	Late	Moderate Budd-Chiari	DUS	Endovascular intervention
		Ascite	ce-MDCT
		Lower extremity edema	Cavography
		Renal dysfunction
		Abdormal liver test function

Clinical characteristics of arterial and caval complications. rLT: Re-liver transplantation; DUS: Doppler ultrasound; HAT: Hepatic artery thrombosis; HAS: Hepatic artery stenosis; HAP: Hepatic artery pseudoaneurysm; HAR: Hepatic artery rupture; PVT: Portal vein thombosis; PVS: Portal vein stenosis; MDCT: Multi-detector computed tomography.

Table 2 Hepatic artery thrombosis highlights

Summary of the clinical characteristics about HAT
HA supplies exclusively the bile duct, so HAT is associated with a high frequency of biliary complications
HAT represents more than 50% of all arterial complications following OL
The incidence of HAT following OLT is 3.5% with early and late HAT incidences of 2.9% and 2.2%, respectively
HAT carries an incidence of graft failure and mortality of more than 50% without prompt treatment
The median time to detection of early and late HAT was 6.9 d (range: 1-17.5 POD) and 6 mo (range: 1.8-79 mo), respectively
No differences in HAT incidences were observed between DDLT and LDLT
Clinical presentation spectrum: Mild elevation of serum transaminase and bilirubin levels (75%), biliary complications (15%), fever and sepsis (6%), graft dysfunction or failure (4%)
Risk factors of early HAT are mainly represented by technical problems, LDLT, cigarette smoking and hypercoagulability state, while late HAT is usually related to ischemic or immunologic injury: CMV positive donor, female donor and male recipient and hepatitis C seropositive recipient
Early diagnosis is achieved by assessing the serum transaminase level and performing Doppler ultrasound monitoring in the postoperative period and confirmed by contrast-enhanced abdominal CT scan and/or visceral angiography
Currently, the literature on the curative management of early HAT suggests the following procedures: First endovascular radiological intervention (IAT, PTA and stent placement), secondly open surgical revascularization, and finally retransplantation, which is associated with the best survival rate compared with revision or thrombolysis, but is a limited therapeutic option due to organ shortage

HA: Hepatic artery; HAT: Hepatic artery thrombosis; OLT: Orthotopic liver transplantation; DDLT: Deceased donor liver transplantation; LDLT: Living donor liver transplantation; CMV: Cytomegalovirus; IAT: Intra-arterial thrombolysis; PTA: Percutaneous transluminal angioplasty; CT: Computed tomography.

Table 3 Hepatic artery stenosis highlights

Summary of the clinical characteristics about HAS
Significant HAS is defined as a narrowing of the transverse diameter > 50% on the angiogram associated with clinical suspicion, with a resistive index < 0.5 and a peak systolic velocity > 400 cm/s detected by DUS
HAS occurs in 2% to 13% of transplants, at the level of the anastomosis (59% of cases), graft HA (41%) or recipient HA (2.6%)
HAS has been speculated to progress to HAT in 65% of cases at 6 mo for untreated HAS
The median time to diagnosis is 100 (range: 1-1220) d following OLT
Most of patients with HAS are asymptomatic and most commonly present only with abnormal liver function tests and in rare cases with graft failure
Routine screening by DUS during the postoperative period is mandatory because of the insidious clinical presentation
The risk factors are not really known, but among these, technical and surgical factors (vascular injury such as clamp injury, intimal dissection, faulty placement of anastomotic sutures, excessive length with kinking and angulation, differences in the vessel caliber that require and oblique anastomosis, vasa vasorum disruption) or acute cellular rejection
DUS is a non-invasive method for the assessment of HA patency, but a contrast-enhanced CT scan and angiography are required to confirm the diagnosis
Radiological endovascular intervention by PTA with or without stent placement is often used to treat post-transplant HAS and are both efficacious, with 7% to 12% of complications including dissection and arterial rupture, restenosis or thrombosis (25%) and 12% failed attempts
Surgical revision and retransplant showed a high rate of success, but the overall mortality rate was as high as 20%. In some case, HAS may be an early sign of chronic rejection

DUS: Doppler ultrasound; HA: Hepatic artery; HAT: Hepatic artery thrombosis; HAS: Hepatic artery stenosis; OLT: Orthotopic liver transplantation; PTA: Percutaneous transluminal angioplasty; CT: Computed tomography.

Table 4 Hepatic artery pseudoaneurysm highlights

Summary of the clinical characteristics about HAP
The reported incidence of HAP is ranging from 0.27% to 3% following OLT
In most cases, HAP is localized extra-hepatic and occurred in the early postoperative period around 1 mo post-OLT (69% within 20 d and 81% within 35 POD)
Clinical presentation varies from the asymptomatic state and incidental diagnosis to abdominal pain with fever and gastrointestinal bleeding (25% of cases, massive bleeding through the abdominal drain or acutely with hemorrhagic shock)
Risk factors include peritoneal infection, biliary leak, bilbo-digestive anastomosis and digestive leak
Diagnosis of HAP is confirmed by DUS (with lower performance), contrast-enhanced CT scan, magnetic resonance angiography or angiography
Treatment of HAP includes reoperation (urgent laparotomy for HA ligation: Mortality rate 60%; HAP excision and immediate revascularization with a cryopreserved arterial allograft: Mortality rate 28%) or interventional radiology (HA embolization with a coil or HAP exclusion with a covered stent)
HAP has a worse prognosis with an overall mortality of more than 50% (ranging from 53% to 100%)
Early recognition of HAP in the population at high risk is mandatory and allows for a successful therapeutic outcome in 100% of cases

DUS: Doppler ultrasound; HA: Hepatic artery; HAP: Hepatic artery pseudoaneurysm; OLT: Orthotopic liver transplantation; CT: Computed tomography.

Table 5 Hepatic artery rupture highlights

Summary of the clinical characteristics about HAR
HAT is defined as a severe hemorrhage from the trunk or from a main branch of the HA, resulting in disruption of graft arterial blood supply
This is a very rare (incidence of 0.64%) but a dramatic complication following OLT with a high mortality rate
In most cases, HAR complicates a pseudoaneurysm of the HA
The median time of HAR is 29 d (range: 2-92 d) following OLT
The clinical presentation is always a sudden hemorrhage: Hemoperitoneum, gastrointestinal bleeding, hematoma and hemobilia
Treatment comprises urgent laparotomy with definitive ligation of the HA, anastomotic revision and aortohepatic grafting or interventional radiology with percutaneous embolization

HA: Hepatic artery; HAT: Hepatic artery thrombosis; OLT: Orthotopic liver transplantation; HAR: Hepatic artery rupture.

Table 6 Portal vein thombosis highlights

Summary of the clinical characteristics about PVT
The incidence of PVT is uncommon and ranges from < 3% following OLT
PVT incidence is higher in pediatric transplantation, LDLT and split liver transplantation
Early PVT is more frequent than late PVT with a median time to diagnosis of 5 d following OLT (range: 1 to 15 d)
The clinical presentation of early PVT ranges from portal hypertension manifestations (abdominal pain, ascites, gastrointestinal bleeding, splenomegaly) to severe allograft dysfunction and multiorgan failure
The most common causes leading to PVT are technical errors and anatomic complications such as venous redundancy, kinking and/or stenosis of the anastomosis
Risk factors are the presence of portal thrombosis prior OLT, small diameter of the portal vein, previous splenectomy, large portosystemic collaterals and the use of cryopreserved venous conduits for PV reconstruction
DUS, CEUS, contrast-enhanced CT, MRI and portography are imaging tools used for a positive diagnosis
PVT treatment includes systemic anticoagulation therapy, catheter-based thrombolytic therapy by percutaneous radiological intervention (transhepatic or transjugular access depending of the coagulation state) with or without stent placement to portosystemic shunting (TIPS) to retransplantation in highly unresolvable cases
PVT is associated with poor survival without treatment, but with prompt management, outcomes in terms of morbidity and mortality are satisfying

DUS: Doppler ultrasound; PVT: Portal vein thombosis; OLT: Orthotopic liver transplantation; LDLT: Living donor liver transplantation; CEUS: Contrast enhanced ultrasound; MRI: Magnetic resonance imaging; CT: Computed tomography; TIPS: Transjugular intrahepatic portosystemic shunt.

Table 7 Portal vein stenosis highlights

Summary of the clinical characteristics about PVS
The true incidence of PVS is not really known, but is thought to be < 3%
The major complication of PVS is the evolution to PVT if not treated
The majority of patients with PVS are asymptomatic and the diagnosis of stenosis is an incidental finding detected on routine DUS screening
Risk factors of PVS are almost exclusively represented by technical errors, particularly if a tapered anastomosis is required in the case of a vessel size mismatch between donor and recipient
Pre-OLT radiotherapy is another major predisposing factor of PVS
DUS with the finding of a stenosis ratio > 50% or a portal velocity ratio > 3:1 defines PVS. Contrast-enhanced CT and portography are used to confirm the diagnosis
If PVS is asymptomatic, no therapeutic intervention with close surveillance is possible, but anticoagulation therapy is recommended
In patients with clinical manifestations, percutaneous radiological intervention is the method of choice by transhepatic or transjugular access to perform angioplasty with our without stent placement; this prevents recurrence with a high rate of success and low rate of complications

PVT: Portal vein thombosis; PVS: Portal vein stenosis; DUS: Doppler ultrasound; OLT: Orthotopic liver transplantation; CT: Computed tomography.

Table 8 Caval anastomosis complication highlights

Summary of the clinical characteristics about CAC
The incidence of CAC is not known and is thought to be less than 3%
CAC is represented by stenosis, thrombosis and kinking depending on the type of caval anastomosis (cava resection or PB)
Clinical presentation of CAC ranges from lower limb edema, hepatomegaly, ascites, pleural effusions, Budd-Chiari syndrome, liver and renal failure, and hypotension, leading to allograft loss and even death
The main risk factor is a technical error in the creation of the anastomosis, which leads to kinking stenosis and thrombosis
Modified-PB with the three-hepatic vein seems to offer better outcomes because it has been demonstrated to be an efficient and safe method
Diagnosis tools include DUS, contrast-enhanced CT and cavography
Percutaneous radiological intervention is the method of choice via a transjugular approach or transhepatic approach if the anastomosis cannot be catheterized
It includes angioplasty by balloon dilatation and recurrences should be prevented by stent placement

CAC: Caval anastomosis complication; DUS: Doppler ultrasound; CT: Computed tomography; PB: Piggyback.