Impact of hepatic arterial hemodynamics in predicting early hepatic arterial thrombosis in pediatric recipients younger than three yr after living donor liver transplantation

We used Doppler US to evaluate the changes in hepatic arterial hemodynamics that occur following LDLT in pediatric recipients, with a view to assessing the utility of these parameters in predicting early HAT. A retrospective review of 144 pediatric recipients (73 males, 71 females) who underwent routine Doppler US in the first week after LDLT was undertaken, and changes in hepatic arterial hemodynamics were assessed. The HARI and HAPSV were compared in patients with early HAT (defined as occurring in the first postoperative week) and a control group, and the utility of these parameters in predicting early HAT after LDLT was determined. A total of 11 pediatric recipients experienced early HAT, being diagnosed on average four and a half days after LDLT. HARI and HAPSV values were significantly different between the early HAT group and controls. HARI values <0.6 on the day before the onset of early HAT were able to predict HAT development with a sensitivity of 81.8% and specificity of 95.2%. This provides evidence for routine Doppler US examination in these patients and supports consideration of more intensive anticoagulation in these high‐risk patients.     

Clinical features of hepatic artery thrombosis after pediatric liver transplantation

Thrombosis of the hepatic artery (HAT) is a severe complication of liver transplantation, and most cases need regrafting. The aim of this study was to review our experience with this complication. From January 1986 through January 1992, 76 liver transplants were performed in 59 pediatric patients at the Children's Hospital La Paz, Madrid. The diagnosis of HAT was made in 12 cases (15.7%). The common patterns of clinical presentation were: fulminant liver necrosis (5), bile leak due to necrosis of the bile duct (4), and relapsing bacteremia (3). Clinical symptoms of fulminant liver necrosis started within the first 2 weeks after transplantation, with rapid deterioration and steep rises in SGOT and SGPT levels. All these patients were retransplanted on an urgent basis, but only 1 is alive 4 years later. Four patients developed bile leaks 13 to 60 days after transplantation; SGOT, SGPT, and total bilirubin were only slightly increased. Three children were retransplanted electively and are alive with a mean follow-up of 3 years. One exceptional patient had a Roux-en-Y jejunostomy and is doing well 30 months later with his original graft. The 3 remaining children had episodes of septicemia with hepatic abscess, liver infarction, and pleural effusion. Liver function tests were normal, with bilirubin levels below 2 mg/dl. All patients were retransplanted, but only 1 is alive and well 13 months later. In the present series, we found that early HAT produces fulminant clinical deterioration requiring an urgent regraft. Late HAT presenting with either infection or bile leak allows time for treatment by elective retransplantation. The best survival was obtained in the latter group. Correspondence to: J. Vázquez     

Low incidence of hepatic artery thrombosis after pediatric liver transplantation without the use of intraoperative microscope or parenteral anticoagulation

The risk of hepatic artery thrombosis (HAT) after pediatric liver transplantation (PLT) has been reported to range from 0 to 25%. We report our experience focusing on the interrelationships between risk factors, surgical technique and the incidence of HAT after liver transplantation in the pediatric age group. From February 18, 1997 to December 31, 2003, 150 consecutive liver transplants were performed in 132 pediatric patients. There were similar numbers of whole grafts when compared with partial grafts, 80 (53.3%) vs. 70 (46.7%), p = 0.30. Four grafts (2.7%) developed HAT. Of the grafts with HAT, three were successfully revascularized within the first 24 h. Only one graft (0.66%) was lost to HAT. A single surgeon utilizing 3.5-6.0 magnification loupes performed all but one hepatic arterial anastomoses. All patients were followed postoperatively by a daily ultrasound protocol and with anticoagulation of aspirin and alprostadil only. Living and deceased donor left lateral segment grafts had an increased rate of HAT when compared with whole liver grafts. HAT with subsequent graft loss may be minimized in PLT with the use of surgical loupes only, anticoagulation utilizing aspirin, alprostadil, and daily ultrasounds.     

Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18-22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 PM on day 6, and tacrolimus was discontinued at 9:00 PM; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case.     

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.     

Intimal dissection of the hepatic artery after thrombectomy as a cause of graft loss in pediatric living-related liver transplantation

HAT is the main cause of graft loss in pediatric living-related LTx. Revascularization of the graft by thrombectomy and re-anastomosis has been reported to be effective for graft salvage in cases of HAT and should be attempted when potential donors are not available for emergency re-transplantation. Immediate complications secondary to revascularization attempts in cases of HAT are not described. Late complications are mainly related to biliary tree ischemia. We report a case of child who experienced intimal hepatic artery dissection, which extended into intra-hepatic branches of the artery after a thrombectomy with a Fogarty balloon catheter in an attempt to restore arterial flow after HAT. This complication led to acute deterioration of the graft and the need for emergency re-transplantation.     

Microvascular hepatic artery reconstruction in pediatric abdominal transplantation: pearls and pitfalls

The "back-wall first" hepatic artery microanastomosis in pediatric liver transplantation saves lives and reduces morbidity. We describe our technique of hepatic artery reconstruction and offer a systematic and multi-team collaborative approach that optimizes surgical outcomes.     

Hepatic artery reconstruction in pediatric living donor liver transplantation under 10 kg, without microscope use

Enne M, Pacheco-Moreira L, Balbi E, Cerqueira A, Alves J, Valladares MA, Santalucia G, Martinho J-M. Hepatic artery reconstruction in pediatric living donor liver transplantation under 10 kg, without microscope use.
Pediatr Transplantation 2010: 14: 48–51. © 2009 John Wiley & Sons A/S.
Abstract:  Arterial reconstructions are pivotal, particularly in pediatric LDLT. We describe microsurgical reconstruction technique with 6× loupes and the clinical course of the first 23 less than 10 kg recipients in an initial LDLT program at a developing country. From March 2002 to October 2008, 286 liver transplantation were performed in 279 patients at our unit. There were 73 children and 206 adults. Among the children, 23 weighing less than 10 kg were recipients from living donors. Arterial reconstructions were with end-to-end interrupted suture using a 6× magnification loupe, according to the untied suture technique. All patients were prospectively followed by color Doppler ultrasound protocol. In our initial experience there were no arterial complications. With mean 24 months of follow-up, 19 patients (82%) are alive with good graft function. Hepatic artery in LDLT can be safely reconstructed with microsurgical techniques without microscope using, with 6× loupe magnification, and can achieve good results in patients under 10 kg.     

An alternative method of arterial reconstruction in pediatric living donor liver transplantation with the recipient right gastroepiploic artery

The classical method for arterial reconstruction in pediatric living donor liver transplantation using left lateral segment consists of end-to-end anastomosis between the donor left hepatic artery and the recipient right hepatic artery. In the present case, an intra-operative hepatic artery thrombosis occurred because of extensive intima wall dissection of the recipient hepatic artery. The patient was a 6-yr-old boy with fulminant hepatic failure, who underwent living donor partial liver transplantation with left lateral segment from his father. The graft was irrigated by a left hepatic artery and an accessory left hepatic artery from gastric artery, both arteries with diameter of <2 mm. These arteries were anastomosed to the recipient right and left hepatic arteries, respectively. Before performing the bile duct reconstruction it was noted that these anastomoses were occluded by clots of blood. An extensive subintimal dissection of the recipient hepatic artery was the cause of this problem. The creation of a new anastomosis by using a more proximal part of this artery without subintimal dissection was judged impossible. Then, the right gastroepiploic artery was mobilized and an anastomosis was performed with the donor left hepatic artery in an end-to-end fashion. Arterial blood flow to the graft was established successfully and the patient's postoperative recovery was excellent. Fifteen days after the transplantation, an angiotomography demonstrated a good hepatic arterial blood flow. The patient is now alive and well, 4 months after the transplantation. In conclusion, the method of hepatic graft arterialization described here is an important option for patients who undergo living donor or split liver transplantation.     

Reducing the incidence of hepatic artery thrombosis in pediatric liver transplantation: Effect of microvascular techniques and a customized anticoagulation protocol

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986‐2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008‐2012, microvascular techniques were introduced. In E3, 2012‐2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post‐liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.     

Biliary complications of living related pediatric liver transplant patients

Patients who undergo living related left lateral segment liver transplants have been reported to have a high incidence of biliary complications and some studies suggest that most patients will ultimately need operative revision. We reviewed our experience with living related transplantation in pediatric recipients to examine the occurrence of biliary complications and the utility of percutaneous biliary procedures in their management. Over a 10-yr period, 48 living donor transplants were performed in 47 patients. Sixteen patients (33%) had biliary complications. Complications included 10 leaks (20%) and eight strictures (17%). Although leaks were treated predominantly with operation, other biliary complications were treated almost exclusively non-operatively. Self limited leaks that lead to biloma accumulation were most often treated via percutaneous catheter drainage and all strictures were treated using percutaneous transhepatic biliary cholangioplasty and stenting. Sixty-seven percent of biliary complications underwent non-operative biliary intervention. Most strictures were focal anastomotic strictures and were successfully treated with cholangioplasty although multiple interventions were necessary and patients required stenting for an average of 13 months. Three of eight strictures were diffuse in nature and these included the only patient who required retransplantation. Graft survival with respect to biliary complications was 94%; 1 yr, 5 yr and overall patient survival for those with biliary complications was 88, 88 and 81%, and for the entire living related group was 84, 81 and 77%, respectively. Although biliary complications are frequent in pediatric living related transplantation, they are not associated with decreased patient survival. Excepting significant bile leaks, the majority can be treated non-operatively via biliary cholangioplasty and stenting. Strictures are especially amenable to this technique which, in our experience, has been successful at decreasing or postponing the need for retransplantation.     

From living related to in-situ split liver transplantation: how to reduce waiting-list mortality

The insufficient number of suitable cadaveric organs for pediatric recipients is the cause of high pretransplant mortality rates and long waiting times. With the introduction of split and living related liver transplantation, the waiting list mortality rate has dropped from greater than 15% to less than 5% and children are transplanted more rapidly. A 5-year patient and graft survival rate of greater than 80% has been obtained in those centers where split and living related liver transplantations are routinely performed. The data analyzed in this paper show that the only current solution to cadaveric organ shortage is a 'multimodal' approach, where whole liver cadaveric transplantation is associated with split and living related liver transplantation.     

Modified triangular hepatic vein reconstruction for preventing hepatic venous outflow obstruction in pediatric living donor liver transplantation using left lateral segment grafts

HVOO can be a critical complication in pediatric LDLT. The aim of this study was to evaluate a modified triangular technique of hepatic vein reconstruction for preventing HVOO in pediatric LDLT. A total of 298 pediatric LDLTs were performed using a left lateral segment graft by 2 methods for reconstruction of the hepatic vein. In 177 recipients, slit‐shaped anastomosis was indicated with partial clamp of the IVC. A total of 121 recipients subjected to the modified triangular anastomosis with total clamp of the IVC. We compared the incidence of hepatic vein anastomotic complications between these 2 methods. Nine of the 177 cases (5.3%) treated with the conventional technique were diagnosed with outflow obstruction. All 9 cases underwent hepatic vein reconstruction with the slit‐shaped hepatic vein anastomosis. In contrast, there were no cases of outflow obstruction in the 121 cases treated with the modified triangular anastomosis. The modified triangular technique of hepatic vein reconstruction with total clamping of the IVC was useful for preventing HVOO in pediatric LDLT.     

Hepatic artery reconstruction with inferior mesenteric vein graft in pediatric living donor liver transplantation

Abstract:  We report a transplant of the left lateral liver segments with two arteries for a pediatric recipient from a live donor. A six-month-old female patient was diagnosed with liver cirrhosis secondary to biliary atresia and scheduled for LDLT (father as donor). Left lateral hepatectomy was performed at the donor site. The dissection of the left HA, which divided immediately after its origin, showed two branches for segments II and III. The artery for segment III was anastomosed to the recipient HA. The artery for segment II was too short for direct anastomosis with the gastroduodenal artery. After an unsuccessful attempt to use of the recipient's saphenous vein, the recipient's IMV was used as an interposition graft. No post-operative complications were observed. The outcome of this case demonstrates that left lateral segments with two arteries can be successfully used if proper surgical techniques are applied. From this experience we can recommend the IMV as an alternative to the saphenous vein for an interposition graft.     

Antithrombotic management and thrombosis rates in children post–liver transplantation: A case series and literature review

Thrombosis is a major postoperative complication in pediatric liver transplantation. There is marked heterogeneity in prophylactic antithrombotic therapies used, without established guidelines. This review summarizes current worldwide incidence of thrombotic events and compares antithrombotic therapies in children post–liver transplant, with comparison to our institution's experience. Of the twenty‐three articles with sufficient detail to compare antithrombotic regimens, the overall incidence of thrombosis ranged from 2.4% to 17.3%. Incidence of HAT ranged from 0% to 28.1%, of HVT from 0% to 4.7%, of PVT from 1.5% to 11.2%, and of IVC thrombosis from 0% to 2.8%. Re‐transplantation due to thrombosis ranged from 0% to 4.8%. Prophylactic antithrombotic therapies varied between studies, and bleeding complications were infrequently reported. Since 2010, 96 children underwent 100 liver transplants at our institution with thrombosis incidence comparable to international literature (HAT 6%, PVT 5%, IVC 1%, and HVT 0%). Re‐transplantation due to thrombosis occurred in 2% and major bleeding occurred in 10%. The prophylactic antithrombotic therapies used post–liver transplantation in children remain varied. Low rates of thrombosis have been reported with antiplatelet use both with and without anticoagulation. Standard definitions and consistent reporting of bleeding complications are required, in addition to thrombosis rates, so that true risk‐benefit assessment of reported regimes can be understood.     

Perioperative anticoagulation practices for pediatric liver transplantation

Despite continued advancements in perioperative care for pediatric liver transplant (LT), graft‐threatening vascular occlusion events including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) remain a source of significant morbidity and mortality. Perioperative anticoagulation is commonly used for the prevention of HAT and PVT, but evidence‐based guidelines are lacking. The goals of this survey were to determine the frequency of use of an anticoagulation protocol and to describe variation in anticoagulation practices among pediatric LT centers. The study consisted of an online survey distributed to members of SPLIT. The survey focused on institutional anticoagulation practices employed to reduce the incidence of graft and life‐threatening vascular occlusion events. Responses were received from 31 of 39 SPLIT centers. All respondents report using anticoagulation after pediatric LT, and approximately 90% have institutional anticoagulation protocols. Subgroup analysis of high volume pediatric LT centers revealed similar variability in anticoagulation patterns. All participating SPLIT centers reported the use of post‐transplant anticoagulation and nearly all use a protocol. However, there is marked variability in the type and dose of anticoagulation as well as the timing of initiation and duration of therapy across centers.     

Pneumatosis intestinalis following pediatric live‐related liver transplant: A case report and successful conservative approach

PI has been rarely reported following pediatric live‐related liver transplantation. Such a disorder is characterized by accumulation of gas in the bowel wall. The cause of PI has not been yet established; however, it has been strongly linked with steroid therapy. In this report, we present a case of PI following pediatric live‐related liver transplantation that has been successfully managed conservatively.     

A central approach to splenorenal shunt in pediatric living donor liver transplantation

The management of LSRS is a crucial problem to ensure a sufficient PV flow during pediatric LT. Although several techniques have been indicated to solve this problem, a more appropriate approach to LSRS is still needed in pediatric LT. We herein present a modified surgical approach to the ligation of LSRS via the left side of the IVC for a nine‐month‐old boy with severe portal hypertension and a history of Kasai portoenterostomy. LSRS was identified and exposed through the left side of the IVC and the dorsal surface of the pancreas from the superior side of the body of the pancreas. The post‐operative course was uneventful with an excellent PV flow. The central approach for the ligation of LSRS is worth considering as an alternative procedure for a patient with collateral vessels and a history of multiple laparotomies.