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Arterial Complications After Transplantation
CHAPTER 77
Arterial Complications After Transplantation Ali Cheaito • Ronald W. Busuttil
CHAPTER OUTLINE MEDIAN ARCUATE LIGAMENT
PEDIATRIC HEPATIC ARTERY THROMBOSIS
HEPATIC ARTERY THROMBOSIS
HEPATIC ARTERY STENOSIS
Clinical Presentation Diagnosis Management
HEPATIC ARTERY PSEUDOANEURYSM
Vascular complications continue to be a major source of morbidity and mortality after orthotopic liver transplantation (OLT). Arterial complications of OLT threaten outcomes for patients and allografts.1-3 Hepatic arterial thrombosis (HAT) interrupts the allograft's blood supply and produces early graft loss, long-term dysfunction, or patient death, making these surgical complications life threatening. Considering the ongoing scarcity of hepatic allografts, vascular complications can have a profound impact on the application of OLT. Any strategies to prevent these technical complications, reduce graft loss, and decrease retransplantation will have far-reaching effects on the treatment of end-stage liver disease. Hepatic artery stenosis and HAT both carry high rates of morbidity and mortality.4-6 In addition, HAT is a major indication for retransplantation. HAT is the most common hepatic arterial complication and has been reported in 4% to 11% of adult transplants and 11% to 26% of pediatric transplants.1-3,7 Hepatic artery stenosis occurs in 5% to 13% of transplants.5 Hepatic artery aneurysm and hepatic artery rupture are rare vascular complication that can develop after OLT, with a reported incidence of 0.3% to 1.2%,6 but can be life threatening if not recognized and managed appropriately. This chapter will focus of the management of these arterial complications following liver transplantation.
MEDIAN ARCUATE LIGAMENT Median arcuate ligament (MAL) syndrome results from luminal narrowing of the celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous bands of the celiac nervous plexus (Fig. 77-1). In 10% to 50% of cases it
is responsible for significant angiographic celiac trunk compression (Fig. 77-2).8,9 In OLT the presence of celiac compression by MAL is considered to be a risk factor for HAT8,10 and may lead to graft loss. Compression of the celiac axis by the muscular fibers of the diaphragm results in a decrease in celiac artery blood flow. Under normal circumstances, collateral circulation via the superior mesenteric/pancreaticoduodenal system prevents the development of foregut ischemia. However, dissection with ligation of collateral flow in hepatic artery reconstruction during OLT may accentuate the effect of celiac axis compression, which would preclude adequate hepatic arterial flow. Arcuate ligament syndrome in association with OLT was first reported by the University of California at Los Angeles (UCLA) and Mount Sinai transplant centers in 1993.11 The incidence varied from 1.6% to 10%.8,10,12 Intraoperative measurement of donor hepatic arterial blood flow demonstrated a spectrum ranging from significant reduction to complete disruption of flow during the expiratory phase of the respiratory cycle. Paulsen and Klintmalm13 recorded the blood flow through the recipient hepatic artery during OLT. It was found to be 425.7 ± 25.6 mL/min. With the presence of celiac compression, hepatic artery blood flow decreased to values of 200 mL/min through expiration. Surgical division of the MAL resulted in relief of the compression with uniform and adequate blood flow as documented by the flowmeter recordings. In addition to surgical division of the MAL or reconstruction via aortoceliac grafting, retrograde transsplenic celiac dilation has been attempted by several authors, with varying degrees of success. More recently, preoperative endovascular stenting for recipient celiac trunk stenosis has been proposed before pancreaticoduodenectomy or after OLT. This radioguided interventional procedure may be an interesting approach for the 997
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TABLE 77-1 A rterial Complication After Liver Transplant AO Total transplant Adult Pediatric
MAL
LG HA
SA
FIGURE 77-1 n Median arcuate ligament (MAL). AO, Aorta; HA, hepatic artery; LG, left gastric; SA, splenic artery.
N
%
HAT
%
4234 3368 866
80 20.5
203 134 69
5 3.9 7.9
From 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. HAT, Hepatic arterial thrombosis.
TABLE 77-2 F actors Affecting Hepatic Arterial Thrombosis Technical
Medical
HA < 3 mm HA anastomosis other than common HA/branch patch Multiple anastomotic attempts Anomalous HA anatomy (donor or recipient) with reconstruction HA angulation Intimal flap Aggressive HA clamping
Previous HAT Polycythemia/acquired or coagulable state ABO incompatibility Multiple ACR episodes CMV infection Hypotension/ Vasopressors Infection
From 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. ACR, Acute cellular rejection; CMV, cytomegalovirus; HA, hepatic artery; HAT, hepatic arterial thrombosis.
FIGURE 77-2 n Median arcuate ligament causing narrowing of the celiac trunk (arrow).
preoperative management of MAL before OLT, but data are still rare in the literature. Although the clinical importance of the celiac compression syndrome is unclear in the general population, it is critical to recognize the existence of this type of obstruction in liver transplant patients. Proper surgical measures must be taken to restore adequate arterial blood supply to the liver to prevent potential graft loss.
HEPATIC ARTERY THROMBOSIS The liver is unique in that it has a dual blood supply. Although any obstruction to the native liver's arterial flow is followed by development of collateral vessels, in the
newly transplanted liver, attachments that might have served as collaterals have been divided. As a consequence the graft suffers an ischemic injury in the setting of acute HAT that can ultimately lead to loss of the allograft. In a small percentage of patients the clinical course of HAT is more benign. HAT is reported to complicate 4% to 15% of OLTs (Table 77-1) and is generally more frequent after pediatric liver transplantation. Factors associated with HAT include dissection of the hepatic arterial wall, technical imperfections with the anastomosis, celiac stenosis or compression by the MAL, aberrant donor or recipient arterial anatomy, complex back-table arterial reconstruction of the allograft, and high-resistance microvascular arterial outflow caused by rejection or severe ischemia-reperfusion injury (Table 77-2). Although advances in surgical technique have reduced the incidence of HAT, it still remains a serious threat to patient and graft survival. With the use of transarterial chemoembolization as treatment for hepatocellular carcinoma, the hepatic artery can be traumatized, resulting in increased periarterial inflammation, friability, and a predisposition to HAT. In 2002 a technique of early common hepatic arterial vascular occlusion was introduced at UCLA.1 This technique consisted of controlling the common hepatic artery with an atraumatic vascular clamp and ligating the gastroduodenal artery; after this was accomplished, the lobar hepatic arteries were occluded. It was hypothesized that early occlusion of the hepatic arterial inflow would decrease retrograde dissection of the hepatic artery. In addition, up to 20% of OLTs are now performed for
77 Arterial Complications After Transplantation
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TABLE 77-3 F eatures of Hepatic Arterial Thrombosis Early
Late
Fulminant hepatic necrosis Transaminitis Biliary stricture Primary nonfunction Fever
Fever Transaminitis Relapsing bacteremia Cholangitis Bile leak Hepatic abscess
From 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. FIGURE 77-3 n Biliary disruption secondary to hepatic artery thrombosis.
hepatocellular carcinoma,14 a malignancy associated with a generalized hypercoagulable state.3
Clinical Presentation The time of onset of HAT has been correlated with the severity of subsequent complications. HAT is most commonly diagnosed less than 1 month after transplantation. Clinical presentations range from fulminant hepatic failure, recurrent biliary sepsis, or delayed biliary leaks to an asymptomatic presentation with abnormal liver function tests. Arterial thrombosis occurring early after transplantation is more likely to be associated with an aggressive course and a higher rate of allograft loss and patient mortality in comparison to late-onset HAT, which has been described as having a more benign course. Clinical presentations varied from increased serum transaminase level with or without cholestasis to liver abscess and such biliary complications as ischemic biliary lesions, cholangitis, bile duct stenosis, or necrosis. In addition, HAT was associated with initial nonfunction and allograft dysfunction leading to retransplantation. In patients with late HAT, biliary complications (Fig. 77-3) occur more frequently than in patients with early HAT. The complications of HAT vary, depending in part on when in the posttransplant course HAT occurs (Table 77-3). HAT occurring within the first 2 months after transplantation can present with one of three classic syndromes, with the number of patients equally divided among the three groups. First, HAT can cause fulminant hepatic necrosis with sharp rises in the serum transaminase levels leading to secondary hepatic infection, usually cholangitis progressing to the development of liver abscesses or gangrene. HAT in this setting has an overall mortality rate of approximately 75%, with only the retransplanted patients surviving.1,2,15,16 Second, HAT can lead to ischemic necrosis of the bile ducts, resulting in a bile leak, bile peritonitis, and sepsis with a 50% mortality rate. Patients with HAT in the setting of massive hepatic necrosis or bile duct leak usually require retransplantation. Third, HAT can lead to the development of relapsing bacteremia, presumably from recurrent cholangitis and disruption of the “bile-blood” barrier, and requires retransplantation in roughly 60% of cases and is fatal in
30%. Interestingly, survival with normal liver function without the need for retransplantation has been described in this subgroup of patients. Late HAT, occurring more than 6 months after transplantation, has been reported and is responsible for roughly 10% of late graft losses.1,15
Diagnosis Early diagnosis with immediate surgical intervention of HAT is critical for improving the survival of grafts and the prognosis of patients. In clinical practice, arteriography is the gold standard for diagnosing HAT after liver transplantation. However, its application has been restricted because of the high risk involved in transporting patients in critical condition from the intensive care unit to the radiology department. In addition, arteriography is an invasive procedure with potential complications. Doppler ultrasonography has become the primary imaging technique in the initial screening and follow-up of hepatic artery complications due to its portable, inexpensive, and noninvasive nature. Although Doppler ultrasonography has high sensitivity (75% to 100%) in HAT screening17 and is able to detect HAT even before clinical indications arise, it is not yet an ideal tool for diagnosis. The diagnostic accuracy is strongly influenced by many variables, including gastrointestinal gas interference, respiration, diminished hepatic artery flow, and the degree of instrument sensitivity (Fig. 77-4). The judgment of thrombosis can be difficult using Doppler ultrasonography, especially when the hepatic artery is thin or has low-velocity flow. Contrast-enhanced ultrasonography provides quantitative assessment of vascular flow and allows the accurate diagnosis of arterial diseases. Computed tomography (CT) angiography also has proven to be accurate and satisfactory as a second-step examination after duplex ultrasonography in the diagnostic algorithm of adult OLT arterial complications (Fig. 77-5). With the recent availability of multiphase, multislice, CT angiography with multidetector reconstruction at certain institutions, the sensitivity of this examination approaches that of conventional angiography (Fig. 77-6). Decreased invasiveness and contrast injection result in fewer vascular and renal complications when compared with angiography. Finally, gadolinium-enhanced magnetic resonance angiography (MRA) is a noninvasive option that is increasingly more often used for patients capable of
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CHA
SMA
FIGURE 77-4 n Celiomesenteric trunk compression that deve loped hepatic artery stenosis (white arrow). Black arrow, Celiac artery; CHA, common hepatic artery; SMA. superior mesenteric artery.
FIGURE 77-5 n Computed tomography scan shows hepatic arte rial thrombosis at the area of anastomosis (large arrow) with patency of some distal vessels (small arrow), probably due to formation of collateral vessels.
breath-holding. Sadick et al18 report 95% concordance between MRA and operative findings in patients suspected of having mesenteric vascular disease.
Management Treatment of HAT is dependent on the clinical status of the patient. There are three subsets of HAT patients who have been demonstrated to benefit from operative management.
FIGURE 77-6 n Volume-rendered reconstruction image (anterosu perior view) shows hepatic artery thrombosis (arrow).
Patients in fulminant hepatic failure with early HAT require resuscitation, broad-spectrum antibiotics, and expeditious retransplantation. In the United States, acute HAT within the first week after OLT is an absolute indication for relisting a recipient as a status 1 candidate.19 In cases in which a recipient is rapidly decompensating and a replacement graft is not immediately available, anhepatic maneuvers such as allograft hepatectomy with supportive venovenous bypass or end-to-side portacaval shunting with preservation of the retrohepatic inferior vena cava have been applied at our center with success. The metabolic demands of a patient in fulminant liver failure as a result of HAT mandate that the choice of replacement graft be maximally optimized. Reduced-size and extended criteria grafts should be used judiciously to minimize potential morbidity and maximize survival. Recipients with early HAT who are asymptomatic or mildly symptomatic are candidates for graft salvage with operative exploration and arterial reconstruction. The choice of technique for hepatic arterial revascularization is critical. If inflow from the recipient celiac axis is adequate, thrombectomy with revision of the offending segment, whether it is hepatic artery anastomosis or reconstructed replaced graft vasculature, is an option. Revision may require adhesiolysis and foreshortening of a segment of donor artery to prevent kinking and recurrent HAT. If celiac inflow is inadequate, our preference is to use the supraceliac aorta. In adults a primary end-to-side anastomosis or interposition iliac artery graft is used. In infants an interposition graft is necessary. The exploration is not complete until the surgeon is satisfied with the arterial Doppler signal and the adequacy of venous outflow. Consideration may be given to resecting ischemic or necrotic portions of the graft. In addition, we routinely perform biopsy on grossly normal liver. Patients in whom late HAT develops but who have biliary sepsis as a consequence are also best served by retransplantation. Nonoperative techniques address the vascular complication but do not reverse the potentially lethal infectious complications seen in these recipients. These patients may require percutaneous abscess
77 Arterial Complications After Transplantation
drainage or even partial hepatectomy as a temporizing measure to control ischemic necrosis and biliary sepsis while awaiting retransplantation. The use of thrombolytic agents at the time of thrombectomy, with or without continuous hepatic artery infusion postoperatively, has been described; however, there are insufficient data to allow evaluation of its efficacy. Few authors advocate wide application of nonoperative management of minimally symptomatic HAT lesions, whether early or late. As the shortage of deceased donor organs persists, however, nonoperative management in appropriate candidates may have to be given added consideration. Catheter-directed thrombolysis with or without angioplasty or stenting (or both) by an experienced interventional radiologist in lieu of surgery has been effective in some patients with HAT and minimal symptoms. Acute and intermediate lesions have the best response rate. Chronic lesions have been demonstrated to exhibit an initial response; however, long-term patency rates are suboptimal.20 Many centers offering nonoperative therapy administer lytic agents such as tissue plasminogen activator via a celiac artery catheter left in situ for approximately 48 hours. A repeat angiogram to ensure patency is often performed before catheter removal. The patient then receives systemic anticoagulation such as intravenous heparin or low-molecular-weight dextran throughout the hospitalization. The duration and dose of systemic anticoagulation are dependent on the patient’s propensity for the development of recurrent HAT. Life-threatening intraprocedure or postprocedure hemorrhage remains a significant complication of the thrombolytic approach. It is of interest to note that the recent development of stents capable of continuous delivery of local antithrombotic or antiproliferative gene therapy may result in increased efficacy and durability of nonoperative HAT management in the future. Finally, expectant management based on the development of symptoms is proposed for select cases of silent late HAT in which it is presumed that neovascularization has provided arterial inflow and obviates the need for urgent intervention.
PEDIATRIC HEPATIC ARTERY THROMBOSIS Most pediatric OLT recipients have biliary atresia and have undergone a previous surgical procedure before OLT. Some patients have congenital vascular anomalies associated with low weight and malnutrition.1,3,21 The incidence of vascular complications following OLT is higher in children than in adults. HAT is the most common one, having a high mortality particularly when it takes place early after OLT (Fig. 77-7). HAT occurs in 10% to 25% of pediatric recipients.3,17,22 Tan et al23 report that HAT is the leading cause of death in pediatric recipients in the postcyclosporine era. They also note an increased risk in recipients younger than 3 years or those weighing less than 15 kg, as well as with livers obtained from donors weighing less than 15 kg. The clinical
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FIGURE 77-7 n Maximum-intensity-projection image from threedimensional contrast-enhanced magnetic resonance angiogra phy of hepatic arterial thrombosis (arrow).
presentation depends on the timing during the posttransplant course. Early HAT may cause fulminant hepatic necrosis with recipient death unless the child receives another OLT. Several factors have been reported to play a part in the occurrence of HAT, including fluctuations in the coagulation parameters in the days after OLT, cytomegalovirus infection, acute rejection, prolonged cold ischemia time, type of graft (whole, reduced, split or living donor) and type of arterial anastomosis (end-toend arterial or on the aorta with an iliac graft). In children the small size of the arteries is an obvious factor to take into consideration. In isolated HAT the main complications are of two types, sometimes combined in the same patient: acute hepatic necrosis, and ischemic biliary complications resulting in bile leaks and strictures of the extrahepatic or intrahepatic bile ducts. Both complications may be combined with severe sepsis and be life threatening: acute hepatic necrosis may result in liver cell failure or refractory sepsis, and ischemic biliary complications, in refractory bacterial cholangitis and biliary cirrhosis. Because of the severe complications that are the rule after HAT, early detection of thrombosis has become an essential part of the management of children after OLT. Doppler ultrasound examinations of the liver twice daily during the first week and daily examinations during the following week allow detection of thrombosis that can be confirmed by CT scan, arteriography, or surgery. Urgent surgical unclogging of the thrombosed artery has been reported with encouraging results both in adults and in children, with deceased donor grafts and with living donors. The long-term results reported confirm that without successful revascularization of the thrombosed artery, graft survival is only about 30% but indicate that graft survival of nearly 80% can be obtained when revascularization is successful. Although revascularization did not prevent acute necrosis or ischemic biliary complications, it reduced the risk for acute necrosis and liver failure and enabled the consequences of ischemic biliary complications to be treated by
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A
B
FIGURE 77-8 n Axial maximum-intensity-projection (A) and coronal volume-rendering (B) computed tomography angiographic images show a stenosis (arrows) of the hepatic artery, with periportal edema and parenchymal infarcts in the left lobe (diffuse and inhomo geneously hypodense regions).
interventional radiology and biliary surgery. This outcome, combined with retransplantation in case of refractory complications, resulted in a 20-year survival rate of 90% in the population of children whose revascularization proved effective. Similarly, in children with failed or unattempted revascularization, the combination of retransplantation, biliary interventional radiological procedures, and surgery adapted to each child's situation, together with assiduous medical care, enabled the entire population of children with HAT to experience survival identical to that of the population of transplanted children without HAT. Urgent revascularization therefore improves graft survival without hampering patient survival, and best results of successful revascularization are observed when it can be performed within 3 days after OLT. The magnitude of graft salvage by urgent surgical revascularization has been a matter of debate. One third of grafts experiencing HAT before day 15 can be salvaged by emergency surgical revascularization. This strongly supports an active approach to the problem. Substantial progress has been made in reducing the incidence of HAT. The minute diameter of the hepatic artery in small children, which is often less than 3 mm, confronted surgeons with the problem of how to avoid what was predominantly a surgical complication. Microsurgical techniques, the operating microscope, and the avoidance of vascular grafts, combined with growing expertise, have been responsible for a drop in the HAT rate from 11% to 26% in the 1980s to as low at 1.7% in the 1990s. Although various methods of medical management after transplantation, such as anticoagulation, the use of antiplatelet agents, and avoidance of overtransfusion, are commonly practiced, none has proven to be important in the prevention of HAT.
HEPATIC ARTERY STENOSIS Hepatic artery stenosis is one of the most common vascular complications after liver transplantation. Most commonly the stenosis occurs in the donor arteries (Fig. 77-8).
Hepatic artery stenosis may cause graft ischemia, with deterioration of liver function and formation of biliary strictures. Surgical reconstruction has traditionally been the first choice for treatment, but improving interventional radiological technique makes it possible to repair the stenosis without surgery. Its incidence is estimated to be between 1.6% and 8% in adults. The progression of hepatic artery stenosis may result in HAT, which is associated with high morbidity, graft loss, and mortality. Hepatic artery stenosis at or near the site of the hepatic artery anastomosis (Fig. 77-9) may be due to operative technique or vascular clamp injury and predisposes to subsequent HAT. Other causes may include allograft rejection or microvascular injury associated with cold preservation injury. The clinical presentation is usually graft dysfunction or biliary tract complication related to the decreased hepatic blood flow. Interventional vascular procedures are used increasingly as a therapeutic alternative for the treatment of hepatic artery stenosis. Fibrinolysis for early HAT was reported. Several series of balloon dilation with fibrinolysis have been reported for hepatic artery stenosis. However, the success rate of the balloon dilation is questionable. Fibrinolysis and percutaneous transluminal angioplasty have a high early success rate in recanalizing the hepatic artery with relatively few complications compared to surgery. However, when performed alone, they do not ensure adequate mid- to long-term patency, which is needed to ensure a good long-term outcome. Abbasoglu et al24 reported that normal liver function was obtained in 67% of patients after hepatic artery revision by either surgical revision or endovascular intervention. The superiority of vascular stenting over balloon angioplasty alone in patients with coronary artery stenosis after cardiac transplantations has been reported. This technology can be applied to hepatic artery stenosis. The progressive improvements of materials and stent design have produced stents with higher flexibility. Stenting together with improved percutaneous interventional techniques may improve the outcome of arterial complications after liver transplantation. However, only a few cases have been reported so far. In multiple series the
77 Arterial Complications After Transplantation
A
B
1003
C
D FIGURE 77-9 n A, Digital subtraction angiogram (DSA) of the hepatic artery shows a focal hepatic artery stenosis of greater than 70% at the anastomosis (arrow). B, After balloon angioplasty, DSA shows suboptimal results with residual stenosis of greater than 30% and possible dissection (arrow). C, DSA after bare-metal self-expanding stent placement (Xpert stent; Abbott Vascular, Redwood City, California) showing improved flow with no residual stenosis (arrow). D, Early arterial phase demonstrates a pseudoaneurysm of the hepatic artery (arrow).
overall patient survival rate was 78%, similar to the 80% survival rate after surgical hepatic artery revision after liver transplantation reported in the literature.5,8 The invasive radiological approach can be considered for short stenosis, for intrahepatic stenosis not accessible by surgery, and for patients with hostile abdomen following multiple surgeries. In most patients the initial suggestion of hepatic artery stenosis was liver enzyme level elevation. However, 27% of the patients did not show liver enzyme level elevation. Duplex ultrasonography is an important screening tool for hepatic artery stenosis, but it is not diagnostic. An angiogram must be performed for accurate diagnosis and to plan the treatment of a hepatic artery stenosis. Stenting requires minimal lengths of hospital stay and carries a relatively low risk for complications. Most patients are treated with acetylsalicylic acid or clopidogrel bisulfate (Plavix) following the stenting procedure to prevent thrombosis. Nevertheless, restenosis develops in some patients. Combinations of acetylsalicylic acid and clopidogrel bisulfate (Plavix) treatment were seen more often in the patients who had subsequent arterial complication than in patients without complication. Restenosis after hepatic artery revision was reported in up to 26% of patients. Percutaneous stenting can also be used as an adjunct to surgical repair for hepatic artery stenosis. Patients with severe arterial stenosis have a
tendency to develop biliary complications such as strictures or biloma even after successful stenting. In conclusion, percutaneous stenting is an effective treatment of hepatic artery stenosis after liver transplantation. Stenting is well tolerated. It requires short admissions and has excellent short-term success rates. Hepatic artery stenting is useful not only for primary stenosis but also as an adjunct treatment after surgical hepatic artery revision.
HEPATIC ARTERY PSEUDOANEURYSM A hepatic artery aneurysm (HAA) is a rare vascular complication that can develop after OLT, with a reported incidence of 0.3% to 1.2%.25,26 Although the occurrence of HAA is rare after OLT, it is associated with a high mortality rate. The clinical manifestation of HAA is varied, and varied management strategies have been employed. Most HAAs were pseudoaneurysms originating from the anastomosis of the native donor and recipient hepatic artery. Risk factors for the development of intrahepatic pseudoaneurysm were interventional procedures such as liver biopsy, percutaneous transhepatic cholangiography, and the placement of transhepatic drainage catheters. For extrahepatic pseudoaneurysm the most important risk factor was local sepsis. This is
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frequently associated with the formation of a Roux-en-Y hepaticojejunostomy, which creates the potential for colonization of the subhepatic space by enteric organisms. The presence of adhesions or severe portal hypertension is associated with a higher incidence of bowel perforation following OLT and represents a further source of infection. Fungal septicemia, usually from an enteric source, has been identified as a specific risk factor, occurring more frequently in patients with bowel perforation and those with fulminant hepatic failure. Other risk factors include pancreatitis and technical difficulties with the arterial anastomosis. The reported clinical manifestation of HAA varies from asymptomatic to sudden hypovolemic shock from rupture of the HAA. Most intrahepatic HAAs are asymptomatic and are detected incidentally during ultrasound scanning but can cause hemobilia. Intra-abdominal or gastrointestinal hemorrhages from rupture are the most common presentations of extrahepatic HAAs. Various rare presentations have been reported, such as a dropping hematocrit, back pain, fever, obstructive jaundice or abnormal liver function test results, cardiac failure from an arteriovenous fistula, or associated incidental finding in HAT following OLT. Bonham et al27 reported that infected HAAs presented within the first 2 months of OLT and noninfected HAAs presented later. Because the onset and presentation of HAA are unpredictable, the diagnosis is often determined at laparotomy or autopsy. Surgical repair of intrahepatic HAAs is impossible, and retransplantation is usually required. Superselective arterial embolization may be used as a bridging procedure while regrafting is awaited. Long-term antibiotic use is required, and this should be based on microbiological findings if possible. Retransplantation for infected intrahepatic and extrahepatic HAAs is associated with high mortality. Various management strategies have been reported for extrahepatic HAAs, including excision of HAA without revascularization, ligation or embolization without revascularization, and ligation or excision of HAA with immediate revascularization. Ligation, embolization, or excision of the HAA without hepatic artery revascularization will lead to death, liver failure, retransplantation, or an ischemic biliary stricture in up to 70% of cases.
Pearls and Pitfalls • Hepatic arterial complications remain dreadful after orthotopic liver transplantation. They should be suspected in cases of fulminant liver failure, delayed bile leak, or intermittent sepsis of unknown cause after liver transplantation. Accurate diagnosis is assisted by ultrasonography and computed tomography scans. Many factors have contributed to the improved survival of recipients of liver transplants. Among the remaining causes of mortality and serious morbidity, those resulting from technical failures continue to pose serious challenges to surgeons undertaking the procedure. The most common and potentially the most devastating of these technical failures is thrombosis of the arterial supply of the hepatic allograft. Many patients have a fulminant clinical course; there are also patients in whom the course is subtle and indolent.
Regardless of the presentation, recognition of the cause is important to patient survival. • The importance of technical perfection cannot be overemphasized. Simplified methods of reconstruction should help in avoiding technical errors. Recently at UCLA early arterial clamping has proven to be successful in reducing technical errors. Patients at highest risk are pediatric patients and those requiring complex vascular reconstructions. • Advances in imaging as well as in interventional radiology have helped in diagnosis and therapeutic approaches to various complications.
REFERENCES 1. 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 May;208(5):896-903. 2. Geissler I, Lamesch P, Witzigmann H, et al. Splenohepatic arterial steal syndrome in liver transplantation: Clinical features and management. Transpl Int. 2002;15:139-141. 3. Vivarelli M, LaBarba G, Legnani C, et al. Repeated graft loss caused by recurrent hepatic artery thrombosis after liver transplantation. Liver Transpl. 2003;9:629-631. 4. Sopher M, Braunfeld M, Shackleton C, et al. Fatal pulmonary embolism during liver transplantation. Anesthesiology. 1997;87: 429-432. 5. Inomoto T, Nishizawa F, Sasaki H, et al. Experiences of 120 microsurgical reconstructions of hepatic artery in living related transplantation. Surgery. 1996;119:20-26. 6. Raby N, Karani J, Thomas S, et al. Stenosis of vascular anastomoses after hepatic transplantation: Treatment with balloon angioplasty. Am J Radiol. 1991;157:167-171. 7. Yanaga K, Lebeau G, Marsh W, et al. Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation. Arch Surg. 1990;125:628-631. 8. Fukuzawa K, Schwartz ME, Katz E, et al. The arcuate ligament syndrome in liver transplantation. Transplantation. 1993;56:223-224. 9. Szilagyi DE, Rian RL, Elliot JP, et al. The celiac artery compression syndrome: Does it exist? Surgery. 1972;72:849-863. 10. Lindner HH, Kemprud E. A clinicoanatomic study of the arcuate ligament of the diaphragm. Arch Surg. 1971;103:600-605. 11. Drazan K, Shaked A, Olthoff KM, et al. Etiology and management of symptomatic adult hepatic artery thrombosis after orthotopic liver transplantation. Am Surg. 1996;62:237-240. 12. Reuter SR. Accentuation of celiac compression by the median arcuate ligament of the diaphragm during deep expiration. Radiology. 1971;98:561-564. 13. Paulsen AW, Klintmalm GB. Direct measurement of hepatic blood flow in native and transplanted organs, with accompanying systemic hemodynamics. Hepatology. 1992;16(1):100-111. 14. Lallier M, Dickens S, Dubois J, et al. Vascular complications after pediatric liver transplantation. J Pediatr Surg. 1995;30: 1122-1126. 15. Hong JC, Yersiz H, Farmer DG, et al. Longterm outcomes for whole and segmental liver grafts in adult and pediatric liver transplant recipients: a 10-year comparative analysis of 2,988 cases. J Am Coll Surg. 2009 May;208(5):682-689. discussion 689-91. doi: 10.1016/j. jamcollsurg.2009.01.023. Epub 2009 Mar 26. 16. Tzakis AG, Gordon RD, Shaw BW, et al. Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation. 1985;40:667-671. 17. Bhattacharjya S, Gunson B, Mirza D, et al. Delayed hepatic artery thrombosis in adult liver transplantation—a 12-year experience. Transplantation. 2001;71:1592-1596. 18. Sadick M, Diehl SJ, Lehmann KJ, et al. Evaluation of breath-hold contrast-enhanced 3D magnetic resonance angiography technique for imaging visceral abdominal arteries and veins. Invest Radiol. 2000;5:111-117. 19. Hashikura Y, Kawasaki S, Okumura N, et al. Prevention of hepatic artery thrombosis in pediatric liver transplantation. Transplantation. 1995;60:1109-1112.
77 Arterial Complications After Transplantation 20. McDiarmid SV, Hall TR, Grant EG. Failure of duplex sonography to diagnose hepatic artery thrombosis in a high-risk group of pediatric liver transplant recipients. Transplant Proc. 1990;22: 1529-1530. 21. Nakazato PZ, Cox KL, Concepcion W, et al. Revascularization technique for reduced-size liver transplantation for infants weighing less than 10 kg. J Pediatr Surg. 1993;28:923-926. 22. Hall T, McDiarmid S, Grant E, et al. False-negative duplex Doppler studies in children with hepatic artery thrombosis after liver transplantation. AJR Am J Roentgenol. 1990;154:573-575. 23. Tan KC, Yandza T, de Hemptinne B, et al. Hepatic artery thrombosis in pediatric liver transplantation. J Pediatr Surg. 1988;23: 927-930.
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24. Abbasoglu O, Levy MF, Vodapally MS, et al. Hepatic artery stenosis after liver transplantation--incidence, presentation, treatment, and long term outcome. Transplantation. 1997;63(2):250-255. 25. Rolando N, Harvy F, Brahm J, et al. Fungal infection: a common, unrecognised complication of acute liver failure. J Hepatol. 1991;12: 1-9. 26. Zajko AB, Chablani V, Bron KM, et al. Haemobilia complicating transhepatic catheter drainage in liver transplant recipients: management with selective embolization. Cardiovasc Intervent Radiol. 1990;13:285-288. 27. Bonham CA, Kapur S, Geller D, et al. Excision and immediate revascularization for hepatic artery pseudoaneurysm following liver transplantation. Transplant Proc. 1999;31(1-2):43.
Arterial Complications After Transplantation Ali Cheaito • Ronald W. Busuttil
CHAPTER OUTLINE MEDIAN ARCUATE LIGAMENT
PEDIATRIC HEPATIC ARTERY THROMBOSIS
HEPATIC ARTERY THROMBOSIS
HEPATIC ARTERY STENOSIS
Clinical Presentation Diagnosis Management
HEPATIC ARTERY PSEUDOANEURYSM
Vascular complications continue to be a major source of morbidity and mortality after orthotopic liver transplantation (OLT). Arterial complications of OLT threaten outcomes for patients and allografts.1-3 Hepatic arterial thrombosis (HAT) interrupts the allograft's blood supply and produces early graft loss, long-term dysfunction, or patient death, making these surgical complications life threatening. Considering the ongoing scarcity of hepatic allografts, vascular complications can have a profound impact on the application of OLT. Any strategies to prevent these technical complications, reduce graft loss, and decrease retransplantation will have far-reaching effects on the treatment of end-stage liver disease. Hepatic artery stenosis and HAT both carry high rates of morbidity and mortality.4-6 In addition, HAT is a major indication for retransplantation. HAT is the most common hepatic arterial complication and has been reported in 4% to 11% of adult transplants and 11% to 26% of pediatric transplants.1-3,7 Hepatic artery stenosis occurs in 5% to 13% of transplants.5 Hepatic artery aneurysm and hepatic artery rupture are rare vascular complication that can develop after OLT, with a reported incidence of 0.3% to 1.2%,6 but can be life threatening if not recognized and managed appropriately. This chapter will focus of the management of these arterial complications following liver transplantation.
MEDIAN ARCUATE LIGAMENT Median arcuate ligament (MAL) syndrome results from luminal narrowing of the celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous bands of the celiac nervous plexus (Fig. 77-1). In 10% to 50% of cases it
is responsible for significant angiographic celiac trunk compression (Fig. 77-2).8,9 In OLT the presence of celiac compression by MAL is considered to be a risk factor for HAT8,10 and may lead to graft loss. Compression of the celiac axis by the muscular fibers of the diaphragm results in a decrease in celiac artery blood flow. Under normal circumstances, collateral circulation via the superior mesenteric/pancreaticoduodenal system prevents the development of foregut ischemia. However, dissection with ligation of collateral flow in hepatic artery reconstruction during OLT may accentuate the effect of celiac axis compression, which would preclude adequate hepatic arterial flow. Arcuate ligament syndrome in association with OLT was first reported by the University of California at Los Angeles (UCLA) and Mount Sinai transplant centers in 1993.11 The incidence varied from 1.6% to 10%.8,10,12 Intraoperative measurement of donor hepatic arterial blood flow demonstrated a spectrum ranging from significant reduction to complete disruption of flow during the expiratory phase of the respiratory cycle. Paulsen and Klintmalm13 recorded the blood flow through the recipient hepatic artery during OLT. It was found to be 425.7 ± 25.6 mL/min. With the presence of celiac compression, hepatic artery blood flow decreased to values of 200 mL/min through expiration. Surgical division of the MAL resulted in relief of the compression with uniform and adequate blood flow as documented by the flowmeter recordings. In addition to surgical division of the MAL or reconstruction via aortoceliac grafting, retrograde transsplenic celiac dilation has been attempted by several authors, with varying degrees of success. More recently, preoperative endovascular stenting for recipient celiac trunk stenosis has been proposed before pancreaticoduodenectomy or after OLT. This radioguided interventional procedure may be an interesting approach for the 997
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TABLE 77-1 A rterial Complication After Liver Transplant AO Total transplant Adult Pediatric
MAL
LG HA
SA
FIGURE 77-1 n Median arcuate ligament (MAL). AO, Aorta; HA, hepatic artery; LG, left gastric; SA, splenic artery.
N
%
HAT
%
4234 3368 866
80 20.5
203 134 69
5 3.9 7.9
From 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. HAT, Hepatic arterial thrombosis.
TABLE 77-2 F actors Affecting Hepatic Arterial Thrombosis Technical
Medical
HA < 3 mm HA anastomosis other than common HA/branch patch Multiple anastomotic attempts Anomalous HA anatomy (donor or recipient) with reconstruction HA angulation Intimal flap Aggressive HA clamping
Previous HAT Polycythemia/acquired or coagulable state ABO incompatibility Multiple ACR episodes CMV infection Hypotension/ Vasopressors Infection
From 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. ACR, Acute cellular rejection; CMV, cytomegalovirus; HA, hepatic artery; HAT, hepatic arterial thrombosis.
FIGURE 77-2 n Median arcuate ligament causing narrowing of the celiac trunk (arrow).
preoperative management of MAL before OLT, but data are still rare in the literature. Although the clinical importance of the celiac compression syndrome is unclear in the general population, it is critical to recognize the existence of this type of obstruction in liver transplant patients. Proper surgical measures must be taken to restore adequate arterial blood supply to the liver to prevent potential graft loss.
HEPATIC ARTERY THROMBOSIS The liver is unique in that it has a dual blood supply. Although any obstruction to the native liver's arterial flow is followed by development of collateral vessels, in the
newly transplanted liver, attachments that might have served as collaterals have been divided. As a consequence the graft suffers an ischemic injury in the setting of acute HAT that can ultimately lead to loss of the allograft. In a small percentage of patients the clinical course of HAT is more benign. HAT is reported to complicate 4% to 15% of OLTs (Table 77-1) and is generally more frequent after pediatric liver transplantation. Factors associated with HAT include dissection of the hepatic arterial wall, technical imperfections with the anastomosis, celiac stenosis or compression by the MAL, aberrant donor or recipient arterial anatomy, complex back-table arterial reconstruction of the allograft, and high-resistance microvascular arterial outflow caused by rejection or severe ischemia-reperfusion injury (Table 77-2). Although advances in surgical technique have reduced the incidence of HAT, it still remains a serious threat to patient and graft survival. With the use of transarterial chemoembolization as treatment for hepatocellular carcinoma, the hepatic artery can be traumatized, resulting in increased periarterial inflammation, friability, and a predisposition to HAT. In 2002 a technique of early common hepatic arterial vascular occlusion was introduced at UCLA.1 This technique consisted of controlling the common hepatic artery with an atraumatic vascular clamp and ligating the gastroduodenal artery; after this was accomplished, the lobar hepatic arteries were occluded. It was hypothesized that early occlusion of the hepatic arterial inflow would decrease retrograde dissection of the hepatic artery. In addition, up to 20% of OLTs are now performed for
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TABLE 77-3 F eatures of Hepatic Arterial Thrombosis Early
Late
Fulminant hepatic necrosis Transaminitis Biliary stricture Primary nonfunction Fever
Fever Transaminitis Relapsing bacteremia Cholangitis Bile leak Hepatic abscess
From 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. FIGURE 77-3 n Biliary disruption secondary to hepatic artery thrombosis.
hepatocellular carcinoma,14 a malignancy associated with a generalized hypercoagulable state.3
Clinical Presentation The time of onset of HAT has been correlated with the severity of subsequent complications. HAT is most commonly diagnosed less than 1 month after transplantation. Clinical presentations range from fulminant hepatic failure, recurrent biliary sepsis, or delayed biliary leaks to an asymptomatic presentation with abnormal liver function tests. Arterial thrombosis occurring early after transplantation is more likely to be associated with an aggressive course and a higher rate of allograft loss and patient mortality in comparison to late-onset HAT, which has been described as having a more benign course. Clinical presentations varied from increased serum transaminase level with or without cholestasis to liver abscess and such biliary complications as ischemic biliary lesions, cholangitis, bile duct stenosis, or necrosis. In addition, HAT was associated with initial nonfunction and allograft dysfunction leading to retransplantation. In patients with late HAT, biliary complications (Fig. 77-3) occur more frequently than in patients with early HAT. The complications of HAT vary, depending in part on when in the posttransplant course HAT occurs (Table 77-3). HAT occurring within the first 2 months after transplantation can present with one of three classic syndromes, with the number of patients equally divided among the three groups. First, HAT can cause fulminant hepatic necrosis with sharp rises in the serum transaminase levels leading to secondary hepatic infection, usually cholangitis progressing to the development of liver abscesses or gangrene. HAT in this setting has an overall mortality rate of approximately 75%, with only the retransplanted patients surviving.1,2,15,16 Second, HAT can lead to ischemic necrosis of the bile ducts, resulting in a bile leak, bile peritonitis, and sepsis with a 50% mortality rate. Patients with HAT in the setting of massive hepatic necrosis or bile duct leak usually require retransplantation. Third, HAT can lead to the development of relapsing bacteremia, presumably from recurrent cholangitis and disruption of the “bile-blood” barrier, and requires retransplantation in roughly 60% of cases and is fatal in
30%. Interestingly, survival with normal liver function without the need for retransplantation has been described in this subgroup of patients. Late HAT, occurring more than 6 months after transplantation, has been reported and is responsible for roughly 10% of late graft losses.1,15
Diagnosis Early diagnosis with immediate surgical intervention of HAT is critical for improving the survival of grafts and the prognosis of patients. In clinical practice, arteriography is the gold standard for diagnosing HAT after liver transplantation. However, its application has been restricted because of the high risk involved in transporting patients in critical condition from the intensive care unit to the radiology department. In addition, arteriography is an invasive procedure with potential complications. Doppler ultrasonography has become the primary imaging technique in the initial screening and follow-up of hepatic artery complications due to its portable, inexpensive, and noninvasive nature. Although Doppler ultrasonography has high sensitivity (75% to 100%) in HAT screening17 and is able to detect HAT even before clinical indications arise, it is not yet an ideal tool for diagnosis. The diagnostic accuracy is strongly influenced by many variables, including gastrointestinal gas interference, respiration, diminished hepatic artery flow, and the degree of instrument sensitivity (Fig. 77-4). The judgment of thrombosis can be difficult using Doppler ultrasonography, especially when the hepatic artery is thin or has low-velocity flow. Contrast-enhanced ultrasonography provides quantitative assessment of vascular flow and allows the accurate diagnosis of arterial diseases. Computed tomography (CT) angiography also has proven to be accurate and satisfactory as a second-step examination after duplex ultrasonography in the diagnostic algorithm of adult OLT arterial complications (Fig. 77-5). With the recent availability of multiphase, multislice, CT angiography with multidetector reconstruction at certain institutions, the sensitivity of this examination approaches that of conventional angiography (Fig. 77-6). Decreased invasiveness and contrast injection result in fewer vascular and renal complications when compared with angiography. Finally, gadolinium-enhanced magnetic resonance angiography (MRA) is a noninvasive option that is increasingly more often used for patients capable of
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CHA
SMA
FIGURE 77-4 n Celiomesenteric trunk compression that deve loped hepatic artery stenosis (white arrow). Black arrow, Celiac artery; CHA, common hepatic artery; SMA. superior mesenteric artery.
FIGURE 77-5 n Computed tomography scan shows hepatic arte rial thrombosis at the area of anastomosis (large arrow) with patency of some distal vessels (small arrow), probably due to formation of collateral vessels.
breath-holding. Sadick et al18 report 95% concordance between MRA and operative findings in patients suspected of having mesenteric vascular disease.
Management Treatment of HAT is dependent on the clinical status of the patient. There are three subsets of HAT patients who have been demonstrated to benefit from operative management.
FIGURE 77-6 n Volume-rendered reconstruction image (anterosu perior view) shows hepatic artery thrombosis (arrow).
Patients in fulminant hepatic failure with early HAT require resuscitation, broad-spectrum antibiotics, and expeditious retransplantation. In the United States, acute HAT within the first week after OLT is an absolute indication for relisting a recipient as a status 1 candidate.19 In cases in which a recipient is rapidly decompensating and a replacement graft is not immediately available, anhepatic maneuvers such as allograft hepatectomy with supportive venovenous bypass or end-to-side portacaval shunting with preservation of the retrohepatic inferior vena cava have been applied at our center with success. The metabolic demands of a patient in fulminant liver failure as a result of HAT mandate that the choice of replacement graft be maximally optimized. Reduced-size and extended criteria grafts should be used judiciously to minimize potential morbidity and maximize survival. Recipients with early HAT who are asymptomatic or mildly symptomatic are candidates for graft salvage with operative exploration and arterial reconstruction. The choice of technique for hepatic arterial revascularization is critical. If inflow from the recipient celiac axis is adequate, thrombectomy with revision of the offending segment, whether it is hepatic artery anastomosis or reconstructed replaced graft vasculature, is an option. Revision may require adhesiolysis and foreshortening of a segment of donor artery to prevent kinking and recurrent HAT. If celiac inflow is inadequate, our preference is to use the supraceliac aorta. In adults a primary end-to-side anastomosis or interposition iliac artery graft is used. In infants an interposition graft is necessary. The exploration is not complete until the surgeon is satisfied with the arterial Doppler signal and the adequacy of venous outflow. Consideration may be given to resecting ischemic or necrotic portions of the graft. In addition, we routinely perform biopsy on grossly normal liver. Patients in whom late HAT develops but who have biliary sepsis as a consequence are also best served by retransplantation. Nonoperative techniques address the vascular complication but do not reverse the potentially lethal infectious complications seen in these recipients. These patients may require percutaneous abscess
77 Arterial Complications After Transplantation
drainage or even partial hepatectomy as a temporizing measure to control ischemic necrosis and biliary sepsis while awaiting retransplantation. The use of thrombolytic agents at the time of thrombectomy, with or without continuous hepatic artery infusion postoperatively, has been described; however, there are insufficient data to allow evaluation of its efficacy. Few authors advocate wide application of nonoperative management of minimally symptomatic HAT lesions, whether early or late. As the shortage of deceased donor organs persists, however, nonoperative management in appropriate candidates may have to be given added consideration. Catheter-directed thrombolysis with or without angioplasty or stenting (or both) by an experienced interventional radiologist in lieu of surgery has been effective in some patients with HAT and minimal symptoms. Acute and intermediate lesions have the best response rate. Chronic lesions have been demonstrated to exhibit an initial response; however, long-term patency rates are suboptimal.20 Many centers offering nonoperative therapy administer lytic agents such as tissue plasminogen activator via a celiac artery catheter left in situ for approximately 48 hours. A repeat angiogram to ensure patency is often performed before catheter removal. The patient then receives systemic anticoagulation such as intravenous heparin or low-molecular-weight dextran throughout the hospitalization. The duration and dose of systemic anticoagulation are dependent on the patient’s propensity for the development of recurrent HAT. Life-threatening intraprocedure or postprocedure hemorrhage remains a significant complication of the thrombolytic approach. It is of interest to note that the recent development of stents capable of continuous delivery of local antithrombotic or antiproliferative gene therapy may result in increased efficacy and durability of nonoperative HAT management in the future. Finally, expectant management based on the development of symptoms is proposed for select cases of silent late HAT in which it is presumed that neovascularization has provided arterial inflow and obviates the need for urgent intervention.
PEDIATRIC HEPATIC ARTERY THROMBOSIS Most pediatric OLT recipients have biliary atresia and have undergone a previous surgical procedure before OLT. Some patients have congenital vascular anomalies associated with low weight and malnutrition.1,3,21 The incidence of vascular complications following OLT is higher in children than in adults. HAT is the most common one, having a high mortality particularly when it takes place early after OLT (Fig. 77-7). HAT occurs in 10% to 25% of pediatric recipients.3,17,22 Tan et al23 report that HAT is the leading cause of death in pediatric recipients in the postcyclosporine era. They also note an increased risk in recipients younger than 3 years or those weighing less than 15 kg, as well as with livers obtained from donors weighing less than 15 kg. The clinical
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FIGURE 77-7 n Maximum-intensity-projection image from threedimensional contrast-enhanced magnetic resonance angiogra phy of hepatic arterial thrombosis (arrow).
presentation depends on the timing during the posttransplant course. Early HAT may cause fulminant hepatic necrosis with recipient death unless the child receives another OLT. Several factors have been reported to play a part in the occurrence of HAT, including fluctuations in the coagulation parameters in the days after OLT, cytomegalovirus infection, acute rejection, prolonged cold ischemia time, type of graft (whole, reduced, split or living donor) and type of arterial anastomosis (end-toend arterial or on the aorta with an iliac graft). In children the small size of the arteries is an obvious factor to take into consideration. In isolated HAT the main complications are of two types, sometimes combined in the same patient: acute hepatic necrosis, and ischemic biliary complications resulting in bile leaks and strictures of the extrahepatic or intrahepatic bile ducts. Both complications may be combined with severe sepsis and be life threatening: acute hepatic necrosis may result in liver cell failure or refractory sepsis, and ischemic biliary complications, in refractory bacterial cholangitis and biliary cirrhosis. Because of the severe complications that are the rule after HAT, early detection of thrombosis has become an essential part of the management of children after OLT. Doppler ultrasound examinations of the liver twice daily during the first week and daily examinations during the following week allow detection of thrombosis that can be confirmed by CT scan, arteriography, or surgery. Urgent surgical unclogging of the thrombosed artery has been reported with encouraging results both in adults and in children, with deceased donor grafts and with living donors. The long-term results reported confirm that without successful revascularization of the thrombosed artery, graft survival is only about 30% but indicate that graft survival of nearly 80% can be obtained when revascularization is successful. Although revascularization did not prevent acute necrosis or ischemic biliary complications, it reduced the risk for acute necrosis and liver failure and enabled the consequences of ischemic biliary complications to be treated by
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A
B
FIGURE 77-8 n Axial maximum-intensity-projection (A) and coronal volume-rendering (B) computed tomography angiographic images show a stenosis (arrows) of the hepatic artery, with periportal edema and parenchymal infarcts in the left lobe (diffuse and inhomo geneously hypodense regions).
interventional radiology and biliary surgery. This outcome, combined with retransplantation in case of refractory complications, resulted in a 20-year survival rate of 90% in the population of children whose revascularization proved effective. Similarly, in children with failed or unattempted revascularization, the combination of retransplantation, biliary interventional radiological procedures, and surgery adapted to each child's situation, together with assiduous medical care, enabled the entire population of children with HAT to experience survival identical to that of the population of transplanted children without HAT. Urgent revascularization therefore improves graft survival without hampering patient survival, and best results of successful revascularization are observed when it can be performed within 3 days after OLT. The magnitude of graft salvage by urgent surgical revascularization has been a matter of debate. One third of grafts experiencing HAT before day 15 can be salvaged by emergency surgical revascularization. This strongly supports an active approach to the problem. Substantial progress has been made in reducing the incidence of HAT. The minute diameter of the hepatic artery in small children, which is often less than 3 mm, confronted surgeons with the problem of how to avoid what was predominantly a surgical complication. Microsurgical techniques, the operating microscope, and the avoidance of vascular grafts, combined with growing expertise, have been responsible for a drop in the HAT rate from 11% to 26% in the 1980s to as low at 1.7% in the 1990s. Although various methods of medical management after transplantation, such as anticoagulation, the use of antiplatelet agents, and avoidance of overtransfusion, are commonly practiced, none has proven to be important in the prevention of HAT.
HEPATIC ARTERY STENOSIS Hepatic artery stenosis is one of the most common vascular complications after liver transplantation. Most commonly the stenosis occurs in the donor arteries (Fig. 77-8).
Hepatic artery stenosis may cause graft ischemia, with deterioration of liver function and formation of biliary strictures. Surgical reconstruction has traditionally been the first choice for treatment, but improving interventional radiological technique makes it possible to repair the stenosis without surgery. Its incidence is estimated to be between 1.6% and 8% in adults. The progression of hepatic artery stenosis may result in HAT, which is associated with high morbidity, graft loss, and mortality. Hepatic artery stenosis at or near the site of the hepatic artery anastomosis (Fig. 77-9) may be due to operative technique or vascular clamp injury and predisposes to subsequent HAT. Other causes may include allograft rejection or microvascular injury associated with cold preservation injury. The clinical presentation is usually graft dysfunction or biliary tract complication related to the decreased hepatic blood flow. Interventional vascular procedures are used increasingly as a therapeutic alternative for the treatment of hepatic artery stenosis. Fibrinolysis for early HAT was reported. Several series of balloon dilation with fibrinolysis have been reported for hepatic artery stenosis. However, the success rate of the balloon dilation is questionable. Fibrinolysis and percutaneous transluminal angioplasty have a high early success rate in recanalizing the hepatic artery with relatively few complications compared to surgery. However, when performed alone, they do not ensure adequate mid- to long-term patency, which is needed to ensure a good long-term outcome. Abbasoglu et al24 reported that normal liver function was obtained in 67% of patients after hepatic artery revision by either surgical revision or endovascular intervention. The superiority of vascular stenting over balloon angioplasty alone in patients with coronary artery stenosis after cardiac transplantations has been reported. This technology can be applied to hepatic artery stenosis. The progressive improvements of materials and stent design have produced stents with higher flexibility. Stenting together with improved percutaneous interventional techniques may improve the outcome of arterial complications after liver transplantation. However, only a few cases have been reported so far. In multiple series the
77 Arterial Complications After Transplantation
A
B
1003
C
D FIGURE 77-9 n A, Digital subtraction angiogram (DSA) of the hepatic artery shows a focal hepatic artery stenosis of greater than 70% at the anastomosis (arrow). B, After balloon angioplasty, DSA shows suboptimal results with residual stenosis of greater than 30% and possible dissection (arrow). C, DSA after bare-metal self-expanding stent placement (Xpert stent; Abbott Vascular, Redwood City, California) showing improved flow with no residual stenosis (arrow). D, Early arterial phase demonstrates a pseudoaneurysm of the hepatic artery (arrow).
overall patient survival rate was 78%, similar to the 80% survival rate after surgical hepatic artery revision after liver transplantation reported in the literature.5,8 The invasive radiological approach can be considered for short stenosis, for intrahepatic stenosis not accessible by surgery, and for patients with hostile abdomen following multiple surgeries. In most patients the initial suggestion of hepatic artery stenosis was liver enzyme level elevation. However, 27% of the patients did not show liver enzyme level elevation. Duplex ultrasonography is an important screening tool for hepatic artery stenosis, but it is not diagnostic. An angiogram must be performed for accurate diagnosis and to plan the treatment of a hepatic artery stenosis. Stenting requires minimal lengths of hospital stay and carries a relatively low risk for complications. Most patients are treated with acetylsalicylic acid or clopidogrel bisulfate (Plavix) following the stenting procedure to prevent thrombosis. Nevertheless, restenosis develops in some patients. Combinations of acetylsalicylic acid and clopidogrel bisulfate (Plavix) treatment were seen more often in the patients who had subsequent arterial complication than in patients without complication. Restenosis after hepatic artery revision was reported in up to 26% of patients. Percutaneous stenting can also be used as an adjunct to surgical repair for hepatic artery stenosis. Patients with severe arterial stenosis have a
tendency to develop biliary complications such as strictures or biloma even after successful stenting. In conclusion, percutaneous stenting is an effective treatment of hepatic artery stenosis after liver transplantation. Stenting is well tolerated. It requires short admissions and has excellent short-term success rates. Hepatic artery stenting is useful not only for primary stenosis but also as an adjunct treatment after surgical hepatic artery revision.
HEPATIC ARTERY PSEUDOANEURYSM A hepatic artery aneurysm (HAA) is a rare vascular complication that can develop after OLT, with a reported incidence of 0.3% to 1.2%.25,26 Although the occurrence of HAA is rare after OLT, it is associated with a high mortality rate. The clinical manifestation of HAA is varied, and varied management strategies have been employed. Most HAAs were pseudoaneurysms originating from the anastomosis of the native donor and recipient hepatic artery. Risk factors for the development of intrahepatic pseudoaneurysm were interventional procedures such as liver biopsy, percutaneous transhepatic cholangiography, and the placement of transhepatic drainage catheters. For extrahepatic pseudoaneurysm the most important risk factor was local sepsis. This is
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frequently associated with the formation of a Roux-en-Y hepaticojejunostomy, which creates the potential for colonization of the subhepatic space by enteric organisms. The presence of adhesions or severe portal hypertension is associated with a higher incidence of bowel perforation following OLT and represents a further source of infection. Fungal septicemia, usually from an enteric source, has been identified as a specific risk factor, occurring more frequently in patients with bowel perforation and those with fulminant hepatic failure. Other risk factors include pancreatitis and technical difficulties with the arterial anastomosis. The reported clinical manifestation of HAA varies from asymptomatic to sudden hypovolemic shock from rupture of the HAA. Most intrahepatic HAAs are asymptomatic and are detected incidentally during ultrasound scanning but can cause hemobilia. Intra-abdominal or gastrointestinal hemorrhages from rupture are the most common presentations of extrahepatic HAAs. Various rare presentations have been reported, such as a dropping hematocrit, back pain, fever, obstructive jaundice or abnormal liver function test results, cardiac failure from an arteriovenous fistula, or associated incidental finding in HAT following OLT. Bonham et al27 reported that infected HAAs presented within the first 2 months of OLT and noninfected HAAs presented later. Because the onset and presentation of HAA are unpredictable, the diagnosis is often determined at laparotomy or autopsy. Surgical repair of intrahepatic HAAs is impossible, and retransplantation is usually required. Superselective arterial embolization may be used as a bridging procedure while regrafting is awaited. Long-term antibiotic use is required, and this should be based on microbiological findings if possible. Retransplantation for infected intrahepatic and extrahepatic HAAs is associated with high mortality. Various management strategies have been reported for extrahepatic HAAs, including excision of HAA without revascularization, ligation or embolization without revascularization, and ligation or excision of HAA with immediate revascularization. Ligation, embolization, or excision of the HAA without hepatic artery revascularization will lead to death, liver failure, retransplantation, or an ischemic biliary stricture in up to 70% of cases.
Pearls and Pitfalls • Hepatic arterial complications remain dreadful after orthotopic liver transplantation. They should be suspected in cases of fulminant liver failure, delayed bile leak, or intermittent sepsis of unknown cause after liver transplantation. Accurate diagnosis is assisted by ultrasonography and computed tomography scans. Many factors have contributed to the improved survival of recipients of liver transplants. Among the remaining causes of mortality and serious morbidity, those resulting from technical failures continue to pose serious challenges to surgeons undertaking the procedure. The most common and potentially the most devastating of these technical failures is thrombosis of the arterial supply of the hepatic allograft. Many patients have a fulminant clinical course; there are also patients in whom the course is subtle and indolent.
Regardless of the presentation, recognition of the cause is important to patient survival. • The importance of technical perfection cannot be overemphasized. Simplified methods of reconstruction should help in avoiding technical errors. Recently at UCLA early arterial clamping has proven to be successful in reducing technical errors. Patients at highest risk are pediatric patients and those requiring complex vascular reconstructions. • Advances in imaging as well as in interventional radiology have helped in diagnosis and therapeutic approaches to various complications.
REFERENCES 1. 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 May;208(5):896-903. 2. Geissler I, Lamesch P, Witzigmann H, et al. Splenohepatic arterial steal syndrome in liver transplantation: Clinical features and management. Transpl Int. 2002;15:139-141. 3. Vivarelli M, LaBarba G, Legnani C, et al. Repeated graft loss caused by recurrent hepatic artery thrombosis after liver transplantation. Liver Transpl. 2003;9:629-631. 4. Sopher M, Braunfeld M, Shackleton C, et al. Fatal pulmonary embolism during liver transplantation. Anesthesiology. 1997;87: 429-432. 5. Inomoto T, Nishizawa F, Sasaki H, et al. Experiences of 120 microsurgical reconstructions of hepatic artery in living related transplantation. Surgery. 1996;119:20-26. 6. Raby N, Karani J, Thomas S, et al. Stenosis of vascular anastomoses after hepatic transplantation: Treatment with balloon angioplasty. Am J Radiol. 1991;157:167-171. 7. Yanaga K, Lebeau G, Marsh W, et al. Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation. Arch Surg. 1990;125:628-631. 8. Fukuzawa K, Schwartz ME, Katz E, et al. The arcuate ligament syndrome in liver transplantation. Transplantation. 1993;56:223-224. 9. Szilagyi DE, Rian RL, Elliot JP, et al. The celiac artery compression syndrome: Does it exist? Surgery. 1972;72:849-863. 10. Lindner HH, Kemprud E. A clinicoanatomic study of the arcuate ligament of the diaphragm. Arch Surg. 1971;103:600-605. 11. Drazan K, Shaked A, Olthoff KM, et al. Etiology and management of symptomatic adult hepatic artery thrombosis after orthotopic liver transplantation. Am Surg. 1996;62:237-240. 12. Reuter SR. Accentuation of celiac compression by the median arcuate ligament of the diaphragm during deep expiration. Radiology. 1971;98:561-564. 13. Paulsen AW, Klintmalm GB. Direct measurement of hepatic blood flow in native and transplanted organs, with accompanying systemic hemodynamics. Hepatology. 1992;16(1):100-111. 14. Lallier M, Dickens S, Dubois J, et al. Vascular complications after pediatric liver transplantation. J Pediatr Surg. 1995;30: 1122-1126. 15. Hong JC, Yersiz H, Farmer DG, et al. Longterm outcomes for whole and segmental liver grafts in adult and pediatric liver transplant recipients: a 10-year comparative analysis of 2,988 cases. J Am Coll Surg. 2009 May;208(5):682-689. discussion 689-91. doi: 10.1016/j. jamcollsurg.2009.01.023. Epub 2009 Mar 26. 16. Tzakis AG, Gordon RD, Shaw BW, et al. Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation. 1985;40:667-671. 17. Bhattacharjya S, Gunson B, Mirza D, et al. Delayed hepatic artery thrombosis in adult liver transplantation—a 12-year experience. Transplantation. 2001;71:1592-1596. 18. Sadick M, Diehl SJ, Lehmann KJ, et al. Evaluation of breath-hold contrast-enhanced 3D magnetic resonance angiography technique for imaging visceral abdominal arteries and veins. Invest Radiol. 2000;5:111-117. 19. Hashikura Y, Kawasaki S, Okumura N, et al. Prevention of hepatic artery thrombosis in pediatric liver transplantation. Transplantation. 1995;60:1109-1112.
77 Arterial Complications After Transplantation 20. McDiarmid SV, Hall TR, Grant EG. Failure of duplex sonography to diagnose hepatic artery thrombosis in a high-risk group of pediatric liver transplant recipients. Transplant Proc. 1990;22: 1529-1530. 21. Nakazato PZ, Cox KL, Concepcion W, et al. Revascularization technique for reduced-size liver transplantation for infants weighing less than 10 kg. J Pediatr Surg. 1993;28:923-926. 22. Hall T, McDiarmid S, Grant E, et al. False-negative duplex Doppler studies in children with hepatic artery thrombosis after liver transplantation. AJR Am J Roentgenol. 1990;154:573-575. 23. Tan KC, Yandza T, de Hemptinne B, et al. Hepatic artery thrombosis in pediatric liver transplantation. J Pediatr Surg. 1988;23: 927-930.
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24. Abbasoglu O, Levy MF, Vodapally MS, et al. Hepatic artery stenosis after liver transplantation--incidence, presentation, treatment, and long term outcome. Transplantation. 1997;63(2):250-255. 25. Rolando N, Harvy F, Brahm J, et al. Fungal infection: a common, unrecognised complication of acute liver failure. J Hepatol. 1991;12: 1-9. 26. Zajko AB, Chablani V, Bron KM, et al. Haemobilia complicating transhepatic catheter drainage in liver transplant recipients: management with selective embolization. Cardiovasc Intervent Radiol. 1990;13:285-288. 27. Bonham CA, Kapur S, Geller D, et al. Excision and immediate revascularization for hepatic artery pseudoaneurysm following liver transplantation. Transplant Proc. 1999;31(1-2):43.