The risks of total pancreatectomy and splenic islet autotransplantation

The intraportal site is the most common site for islet transplantation. Many other sites have been tried experimentally, including the spleen, which has successfully lead to insulin independence in a number of animal models. Nevertheless, there are no detailed reports of total pancreatectomy and splenic islet autotransplantation in humans. Five patients underwent total pancreatectomy and splenic islet autotransplantation for chronic pancreatitis. Four patients had a pylorus-preserving total pancreatectomy and one patient a duodenal-preserving pancreatectomy. In three cases islets were embolized into both the portal vein and spleen. Two patients received splenic islet transplants alone. Islets were transplanted by retrograde venous infusion via the short gastric veins (n = 3), splenic vein stump (n = 1), and the left gastroepiploic vein (n = 1). The total volumes of transplanted pancreatic digest in those receiving combined intraportal and splenic autografts (n = 3) were 15.8, 13.0, and 13.5 ml. The volumes in those receiving a splenic-alone autograft (n = 2) were 12.0 and 5 ml. The mean rise in portal pressure was 18 cm of water. Complications related to the splenic autograft included a wedge splenic infarct, an emergency splenectomy, and a portal vein thrombosis in one patient having a combined intraportal and splenic autograft. Two patients developed insulin independence. two patients were still insulin independent at 1-year follow-up, and all had normal HbA1c levels (mean 5.6, range 5.2-6.3). Splenic islet autotransplantation, after total pancreatectomy, does lead to insulin independence. However, in our experience the combined procedure has a high morbidity because of splenic infarction and venous thrombosis.     

Hepatocyte transplantation through the hepatic vein: a new route of cell transplantation to the liver

The efficiency of hepatocyte transplantation into the liver varies with the method of administration. This study investigated whether retrograde infusion via the hepatic vein provides a sufficient number of donor cells for the liver. Donor hepatocytes were isolated from dipeptidyl peptidase IV (DPPIV(+)) rats and transplanted into DPPIV(-) rat livers either by antegrade portal vein infusion or retrograde hepatic vein infusion. Hepatocyte engraftment ratios and localization were evaluated by histological DPPIV enzymatic staining at 1 week and 8 weeks after the transplantation. No significant differences in engraftment efficiency were observed at either 1 week or 8 weeks after transplantation by either route. However, the localization of the transplanted hepatocytes differed with the administration route. Portal vein infusion resulted in predominantly periportal engraftment, whereas hepatic vein infusion led to pericentral zone engraftment. Immunohistochemical analysis showed that the transplanted hepatocytes engrafted in the pericentral zone after retrograde infusion displayed intense CYP2E1 staining similar to the surrounding native hepatocytes. CYP2E1 staining was further enhanced by administration of isosafrole, an inducing agent for various cytochrome P450 enzymes, including CYP2E1. This study demonstrates a novel approach of transplanting hepatocytes into the liver through retrograde hepatic vein infusion as the means to target cell implantation to the pericentral zone.     

Intraportal hepatocyte transplantation in the pig: hemodynamic and histopathological study

BACKGROUND: Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs. METHODS: Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min. RESULTS: The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal. CONCLUSION:. These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.     

Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization

BACKGROUND: Hepatocyte transplantation could be an alternative to whole liver transplantation for the treatment of metabolic liver diseases. However, the results of clinical investigations suggest that the number of engrafted hepatocytes was insufficient to correct metabolic disorders. This may partly result from a lack of proliferation of transplanted hepatocytes. In rodents, portal ligation enhances hepatocyte engraftment after transplantation. We investigated the effects of partial portal ligation and embolization on engraftment and proliferation of transplanted hepatocytes in primates. METHODS: Hepatocyte autotransplantation was performed in Macaca monkeys. The left lateral lobe was resected for hepatocyte isolation. The first group of monkeys underwent surgical ligation of the left and right anterior portal branches; in the second group, the same portal territories were obstructed by embolization with biological glue. To evaluate the proportion of cell engraftment hepatocytes were Hoechst-labeled and transplanted via the portal vein. Cell proliferation was measured by BrdU incorporation. RESULTS: Hepatocyte proliferation was induced by both procedures but it was significantly higher after partial portal embolization (23.5% and 11.2% of dividing hepatocytes on days 3 and 7) than after ligation (3% and 0.8%). Hepatocytes engrafted more efficiently after embolization than after ligation. They proliferated and participated to liver regeneration representing 10% of the liver mass on day seven and their number remained constant on day 15. CONCLUSIONS: These data suggest that partial portal embolization of the recipient liver improves engraftment of transplanted hepatocytes in a primate preclinical model providing a new strategy for hepatocyte transplantation.     

肝移植术中门静脉血栓和瘤栓的处理

目的 探讨肝移植时门静脉血栓和瘤栓的处理方法和临床效果.方法 2000年8月至2004年底我院施行的150例肝移植患者中5例为肝硬化伴门静脉血栓形成,21例为肝癌伴门静脉瘤栓及/或血栓形成,共26例.这些病例在术中清除了门静脉内的栓子,3例又行门静脉壁部分切除及低位门静脉对端吻合术,1例行门腔静脉半转位吻合术.结果 26例中1例术后门静脉又再发血栓形成.21例肝癌合并门静脉瘤栓者,术后近期死亡3例,分别死于：门静脉继发性血栓形成,移植肝原发性无功能和多器官衰竭.18例得到长期随访,术后1、2、3年生存率分别为：66.7%,38.9%,27.8%.结论 肝移植时受体门静脉合并血栓/瘤栓者在清除栓子后再行肝移植仍然可取得较好的疗效.     

Acute portal vein thrombosis secondary to donor/recipient portal vein diameter mismatch after orthotopic liver transplantation: a case report

The incidence of portal vein thrombosis in end-stage liver disease is estimated as varying between 5% and 21%, whereas in candidates undergoing liver transplantation, this is 3-13%. Portal vein thrombosis occurring after liver transplantation can be managed surgically by thrombectomy, retransplantation, splenorenal shunt, or Wall-stent placement, or nonsurgically by angioplasty, local high-dose infusion of thrombolytic agents, combination of portal thrombolysis, or embolization of a pre-existing spontaneous splenorenal shunt. We report a case of portal vein thrombosis after liver transplantation diagnosed on postoperative day 1 in a 57-year-old patient who received a liver from an 8-year-old donor. The patient was successfully treated surgically with portal vein thrombectomy and systemic anticoagulation. Portal vein thrombosis, in this case, was considered to be secondary to size discrepancy between the donor and the recipient portal veins. Routine use of daily Doppler ultrasound was the key factor in early diagnosis.     

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

肝移植术后迟发性门静脉血栓形成12例

目的 总结肝移植术后迟发性门静脉血栓形成的治疗方法,并分析其预后.方法 单中心3100例次尸体全肝移植中发生迟发性门静脉血栓形成12例,发生时间平均为移植术后29.8个月.12例中,2例合并严重胆道并发症(肝内胆道狭窄),2例表现为移植肝功能衰竭,1例影像学检查可见肝门部肿物致门静脉受压,均接受再次肝移植;2例表现为急性上消化道出血,分别行经胃镜下套扎、注射硬化剂治疗;余5例无任何临床表现,口服抗凝或抗血小板药物治疗.结果 12例中,除1例失访外,其他患者至随访结束时存活8例,包括2例行再次肝移植者.存活者肝功能检查结果均正常.结论 肝移植术后发生迟发性门静脉血栓形成,应根据患者的临床表现不同采用不同的治疗方法.

Abstract：

Objective To summary therapeutic method for delayed portal vein thrombosis after liver transplantation. Methods In 3100 cases undergoing cadaveric whole liver transplantation in a single center, there were 12 cases of delayed portal vein thrombosis after liver transplantation.Average occurring time was 29. 8 months after liver transplantation. Among these 12 patients, 2 cases were complicated with severe biliary complication (intrahepatic stricture) , 2 cases presented with liver failure of transplanted liver, and one case had portal vein compression by hepatic hilum tumor under the image examination, who received liver re-transplantation; two patients presented upper gastrointestinal bleeding, and they experienced endoscopic ligation and sclerotherapy respectively; the rest five patients without any clinical presentation were subjected to anticoagulation and antiplatelet therapy. Results Among 12 cases, 8 patients survived by the time of follow-up, including two patients undergoing re-transplantation; one patient lost follow-up. The liver function tests of the patients who survived were all normal. Conclusion The individualized therapeutic methods should be adopted for the patients with delayed portal vein thrombosis after liver transplantation.     

Use of the middle colic vein for liver cell transplantation in infants and small children

INTRODUCTION: Because it is less invasive, intraportal liver cell transplantation (LCT) is an interesting alternative to whole organ transplantation. The inferior mesenteric vein is usually chosen for portal vein access. However, anatomical variations are common in children, so we investigated catheter insertion into the middle colic vein. PATIENTS AND METHODS: Three children (3 weeks to 3 years; 3 to 14 kg) underwent LCT in our center for acute liver failure or severe neonatal urea cycle disorders. Small 4.2-French Hickman lines were surgically introduced into the middle colic vein and advanced to the portal vein stem. The patients received repetitive infusions of liver cells over a period of 4-11 days. RESULTS: Catheter insertion was feasible and tolerated well despite the poor clinical condition of 1 patient and the metabolic instability in the other 2 patients. Blood could be drawn from all catheters, and measurement of portal vein pressure was possible in 2 children. The patient with acute liver failure died after 11 days from complications of the underlying disease. In the other 2 children, portal vein catheters stayed patent for several months. CONCLUSIONS: The middle colic vein can be recommended for placement of intraportal LCT catheters even in small and critically ill infants.     

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.     

Rescue of Acute Portal Vein Thrombosis After Liver Transplantation Using a Cavoportal Shunt at Re-transplantation

BACKGROUND: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options. METHODS: We successfully re-transplanted a 46-year-old female patient who developed acute portal vein thrombosis 19 d after orthotopic liver transplantation. Vascular reconstruction included a cavoportal shunt to augment portal blood flow. RESULTS: Twelve months after re-transplantation this patient lives independently and enjoys excellent liver allograft function. CONCLUSIONS: Cavoportal shunt can augment portal blood flow in adult recipients of orthotopic liver transplants. This technique can be successfully employed during re-transplantation when portal blood flow is inadequate to maintain patency.     

Postshunt encephalopathy in liver transplanted children with portal vein thrombosis

BACKGROUND: Surgical portosystemic shunting has been reported to alleviate successfully portal hypertension in liver transplanted recipients with portal vein thrombosis. METHODS: We report two liver transplanted children with portal vein thrombosis who developed post-shunt acute encephalopathy. In one child, a mesocaval H-type shunt was created surgically because of bleeding related to Roux-en-Y loop varices at 3 months posttransplantation; in the other, a large spontaneous splenorenal shunt was discovered at the time of diagnosis of portal vein thrombosis on day 34 posttransplantation and was preserved. RESULTS: Post-shunt encephalopathy developed 6 months and 2.7 years after transplantation, causing death in one child. CONCLUSIONS: This report illustrates the risk and the possible dismal outcome of post-shunt encephalopathy in liver transplanted children. Therapeutic procedures other than portosystemic shunting that will restore an hepatopetal portal flow to the liver graft should be considered in liver-transplanted children with portal vein thrombosis.     

Current status of hepatocyte transplantation

Hepatocyte transplantation (HT) has been performed in patients with liver-based metabolic disease and acute liver failure as a potential alternative to liver transplantation. The results are encouraging in genetic liver conditions where HT can replace the missing enzyme or protein. However, there are limitations to the technique, which need to be overcome. Unused donor livers to isolate hepatocytes are in short supply and are often steatotic, although addition of N-acetylcysteine improves the quality of the cells obtained. Hepatocytes are cryopreserved for later use and this is detrimental to metabolic function on thawing. There are improved cryopreservation protocols, but these need further refinement. Hepatocytes are usually infused into the hepatic portal vein with many cells rapidly cleared by the innate immune system, which needs to be prevented. It is difficult to detect engraftment of donor cells in the liver, and methods to track cells labeled with iron oxide magnetic resonance imaging contrast agents are being developed. Methods to increase cell engraftment based on portal embolization or irradiation of the liver are being assessed for clinical application. Encapsulation of hepatocytes allows cells to be transplanted intraperitoneally in acute liver failure with the advantage of avoiding immunosuppression. Alternative sources of hepatocytes, which could be derived from stem cells, are needed. Mesenchymal stem cells are currently being investigated particularly for their hepatotropic effects. Other sources of cells may be better if the potential for tumor formation can be avoided. With a greater supply of hepatocytes, wider use of HT and evaluation in different liver conditions should be possible.     

Liver repopulation after hepatocellular transplantation: integration and interaction of transplanted hepatocytes in the host

The mechanisms of donor hepatocyte integration into recipient liver are not fully understood. We investigated mechanisms of both the integration and interaction of transplanted hepatocytes with host liver cells as well as the repopulation of the host organ following intraportal transplantation. Mature hepatocytes were injected into the portal vein of dipeptidylpeptidase IV (DPPIV)-deficient rats pretreated with retrorsine and subjected to 30% partial hepatectomy to ensure selective donor growth. The degree of integration and proliferation was studied by colocalizing transplanted cells (DPPIV positive) with connexin 32, MMP-2, and OX-43 (multilayer immunofluorescence imaging). FACS analysis was established to assess the extent of repopulation quantitatively. Transplanted hepatocytes reached the distal portal spaces and sinusoids within 1 h after injection. A small proportion of cells succeeded in traversing the endothelial barrier through mechanical disruption in both locations. Transplanted hepatocytes lost their membrane-bound gap junctions (connexin 32) during this process. Successful integration of the donor cells required up to 5 days, heralded by gap junction reconstitution and the specific basolateral membrane expression of DPPIV. MMP-2 degraded the extracellular matrix in close proximity to donor cells, providing space for cell division. FACS analysis revealed that more than 37% of the liver was repopulated by cells derived from donors at 2 months after transplantation. Our data demonstrate a high degree of donor cell repopulation of the host organ and provide valuable insight into the specific mechanisms of donor cell integration. Connexin 32 expression in transplanted hepatocytes may serve as an indicator of their effective incorporation and communication within the recipient liver. FACS analysis reveals an accurate method to determine quantitatively the extent of liver repopulation.     

Hepatic artery vs. portal vein infusion of microbeads: a large animal pre‐clinical model evaluating the intrahepatic capacity for cell infusion and imaging

Wang W, Liu S, Zheng W, Gao F, Hawthorne WJ, Yi S. Hepatic artery vs. portal vein infusion of microbeads: a large animal pre‐clinical model evaluating the intrahepatic capacity for cell infusion and imaging. Xenotransplantation 2010; 17: 207–214. © 2010 John Wiley & Sons A/S. Abstract: Background: Islet xeno‐transplantation via the portal vein has been proposed as an alternative of islet allo‐transplantation for treatment of type 1 diabetes. However, the precise hepatic capacity has not been addressed. Methods: We mimicked cell transplantation by infusion of dogs with alginate/poly‐1‐lysine/alginate (APA) microbeads via either the portal vein (PV) or hepatic artery (HA). The maximal adaptable capacity for infused microbeads was evaluated by examination of vasculature, microvasculature, hepatic hemodynamics, portal vein, and hepatic artery pressures and liver function in the microbead recipient dogs. Results: PV but not HA dogs demonstrated elevated portal pressure during the infusion procedure in a dose‐dependent manner. Four out of twelve PV dogs infused with 32 000 microbeads/kg developed acute liver infarction within 24 h after infusion with four of the remaining eight animals developing portal venous thrombosis within 24 h following infusion. All PV animals demonstrated abnormal alanine aminotransferase (ALT) values, and the extent and duration of increased ALT levels correlated with the increase in the number of microbeads infused. In contrast, HA animals infused with as many as 32 000 microbeads/kg had neither portal thrombosis nor abnormal liver function. Conclusions: The capacity for intrahepatic cell infusion is finite and the intrahepatic artery may have a less hemodynamic interference impact on transplantation of cells into the liver when a larger volume of cells is required to achieve curable outcomes in both allo‐ and xeno‐transplantation.     

Human Serum Albumin Microspheres Approximate Initial Organ-Specific Biodistributions of Transplanted Hepatocytes and Are Effective Cell Surrogates for Safety Studies

Liver repopulation with transplanted hepatocytes will generate novel cell-based therapies, although translocation of transplanted cells into lungs through portasystemic shunts has the potential for embolic complications. To facilitate safety analysis of hepatocyte transplantation, we wished to obtain effective cell surrogates and analyzed biodistributions of similarly sized ^99mTc-labeled human serum albumin microspheres and rat hepatocytes. Image analysis with dual ^99mTc and ¹¹¹In labels indicated that cells and microspheres were similarly distributed in the liver when injected into normal rats via the spleen. Also, their distributions were similar when injected via a femoral vein or the superior mesenteric vein with cells and microspheres localizing in lungs or liver, respectively. Upon intraportal injection in rats with portal hypertension, microspheres localized in both liver and lungs, consistent with portasystemic shunting. These data demonstrate that human serum albumin microspheres are effective cell surrogates for approximating the safety of hepatocyte transplantation and should be clinically useful.     

Comparison of Blood Glucose Concentrations After Administration of a Glucose Solution via the Jugular Vein and Portal Vein in Cows

The goals of the present study were to determine whether the infusion of a glucose solution into the portal vein is tolerated in cows and whether the glucose concentration differs after administration of glucose into the jugular vein and portal vein. Fifteen healthy Swiss Braunvieh cows were used. An indwelling catheter was placed in both jugular veins and a balloon‐tipped indwelling catheter with a diameter of 2 mm was placed in the portal vein under the guidance of ultrasonography. Three cows received 500 ml of 20% glucose solution over 60 min via the left jugular vein. Three other cows received the same solution over 60 min via the portal vein. Blood samples were collected from the right jugular vein before and for 24 h after the infusion of glucose for the determination of the concentrations of glucose and bilirubin and the activities of glutamate dehydrogenase, sorbitol dehydrogenase and γ‐glutamyl transferase. Infusion via the portal vein did not result in abnormalities in the general condition of the cows or increases in the concentration of bilirubin or the activities of liver enzymes. The blood glucose concentration increased to the same extent after both intraportal and intrajugular infusion. Over a 12‐h period, three cows received 10 l of 20% glucose solution via the left jugular vein and three others received the same solution over a 12‐h period via the portal vein. Blood samples were collected from the right jugular vein before and for 30 h after the start of infusion. Infusion via the portal vein did not affect the general condition of the cows or the activities of the liver enzymes. There was no significant difference in the blood glucose concentration between the two groups throughout the study.     

Orthotopic liver transplantation: nonoperative management of early, acute portal vein thrombosis

We report a case of acute portal vein thrombosis that occurred 1 week after orthotopic liver transplantation in a patient with sclerosing cholangitis. Unlike other patients reported in the literature who were first seen with variceal bleeding or acute hepatic failure, this patient initially had mild clinical signs, consisting of an abnormal prothrombin time, an increase in liver function test values, and enlarging but nonbleeding gastroesophageal varices. Whereas patients with more extreme symptoms often die or require retransplantation, this patient was managed nonoperatively. Spontaneous lysis of the portal vein thrombus occurred over the ensuing 2 weeks. The diagnosis and management of this milder form of early, acute portal vein thrombosis are discussed.     

Intraportal infusion of 99mtechnetium-macro-aggregrated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes

BACKGROUND: Partial correction of metabolic liver disease by hepatocyte transplantation requires infusion of a large number of cells into the portal vein. Uncontrolled infusion of cells leads to extrahepatic shunting. Obstruction of the sinusoidal space may result in hemodynamic changes and impairment of liver function. METHODS: Catheters connected to a port were placed into the caudal mesenteric vein of rabbits. After injection of 99mtechnetium-macroaggregated albumin (99mTc-MAA) surrogates or 99mTc-MAA/hepatocyte (Hc) mixtures (1:125), shunting into the lung was scintigraphically monitored. Volume flow (mL/min) and maximum velocity of the portal vein were recorded by color-coded Doppler ultrasound during intraportal application of 2.5 x 10(7) MAA particles, 2.5 x 10(7) isolated hepatocytes, and saline solution without particles or cells. RESULTS: 99mTc-MAA particles (2.5 x 10(7)) or equivalent MAA/Hc mixtures were completely retained in the liver. With additional application of 2.5 x 10(7) particles, shunting into the lung was observed in two animals of the MAA group. All animals in the hepatocyte group have received 5 x 10(7) MAA/Hc mixtures, and three of these received 10(8) mixtures without shunting. Maximum velocity and volume flow increased with saline infusion. Hepatocyte suspended in the same volume blunted the increase observed in the control group, but parameters remained normal. Liver enzymes increased after hepatocyte application but returned to normal values within 5 days. CONCLUSIONS: Sinusoidal uptake capacity for hepatocyte or MAA particles varies at a wide range in normal rabbits. Scintigraphic monitoring of transplanted cells allows efficient monitoring of cell translocation into the lungs. No significant impairments of portal hemodynamics and liver function were detected.     

Management of Acute Portal Vein Thrombosis With Serial Mechanical Thrombectomy and tPA in a Pediatric Liver Transplant Recipient: A Case Report

BackgroundAcute portal vein thrombosis is a major cause of fulminant allograft failure in pediatric liver transplantation. Timely intervention is critical to save the graft and patient. Serial interventional radiologic management of this condition is scarcely reported in the literature.Case SummaryA recently transplanted 17-year-old male presented to the emergency department with abdominal pain. Rising liver enzymes prompted discovery of a diffuse portal thrombus, which precipitated fulminant liver failure. The adolescent developed respiratory failure, vasodilatory shock, acute kidney injury, and hepatic encephalopathy, complicating treatment. Multiple interventions attempted to clear the thrombus, including interventional radiologic and medical therapies. Uniquely, a continuous infusion catheter was placed at the thrombosis, delivering local tissue plasminogen activator during a 5-day period. Upon thrombus clearance, the patient made a full recovery with no complications during 12 months of follow-up.ConclusionsWhen used as a component of multidisciplinary management, continuous locally directed tissue plasminogen activator may be a useful tool for clearance of persistent portal vein thrombosis.