Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co-localized inside the thrombus.     

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.     

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.     

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver. Received: 15 September 1997 Received after revision: 4 February 1998 Accepted: 2 March 1998     

Simultaneous hepatic artery and portal vein thrombosis after living donor liver transplantation

Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.     

血管内介入治疗肝移植术后门静脉狭窄或闭塞:5例报告

目的 观察血管内介入治疗肝移植术后门静脉狭窄或闭塞的效果。方法 对肝移植后3例门静脉狭窄及2例闭塞患者行血管内介入治疗,观察治疗效果。结果 对3例门静脉狭窄、1例门静脉闭塞行球囊扩张及支架植入术,术后造影示狭窄消失,血流通畅;对1例门静脉闭塞行球囊扩张并置管溶栓术,术后3天造影示门静脉通畅,血栓减少。1例术中发生肋间动脉出血,未见门静脉治疗相关并发症。术后4例症状逐渐消失、肝功能逐步恢复,随访期间门静脉通畅,1例支架内见少许附壁血栓;1例术后胆总管狭窄,植入胆道支架后,因重症肺炎、急性呼吸窘迫综合征、脓毒性休克死亡。结论 血管内介入治疗肝移植术后门静脉狭窄或闭塞效果良好;对移植后急性血栓形成可行球囊扩张术联合置管溶栓。     

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.     

儿童肝移植20例诊治分析

目的 总结儿童肝移植的临床疗效,探讨儿童肝移植在适应证、手术方式及术后处理等方面的特点.方法 2000年8月至2007年7月对20例儿童(＜14岁)施行肝移植手术23次,患儿年龄6个月～13岁,原发疾病主要包括先天性胆道闭锁、Wilson病、肝糖原累积症和尿素循环障碍.手术方式采用亲体部分肝移植4次,多米诺肝移植1次,劈离式肝移植5次,减体积肝移植10次和尸体全肝移植3次.除1例患儿应用环孢霉素外,其余19例患儿均应用他克莫司,联合激素及霉酚酸酯三联免疫抑制方案.结果 患儿围手术期内死亡3例(15.0%),死亡原因分别为移植肝原发无功、心功能衰竭和腹腔感染.9例患儿术后出现不同的并发症,包括肝动脉血栓形成2例、门静脉血栓形成1例、急性排斥反应1例、胆漏3例、胆道狭窄2例、肠瘘2例、腹腔感染3例、肺感染1例和心功能衰竭1例.患儿术后6个月、1年和2年累积生存率分别为80.0%、73.9%和73.9%.结论 肝移植是治疗儿童终末期肝病的有效方法,手术方式可根据患儿的年龄、体重进行选择.     

Portosystemic shunts in children: a 15-year experience

BACKGROUND: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding. STUDY DESIGN: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed. RESULTS: There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty. CONCLUSIONS: PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.     

Improving hepatic and portal venous flows using tissue expander and Foley catheter in liver transplantation

BACKGROUND AND OBJECTIVE: Vascular reconstruction is important in liver transplantation because its obstruction causes graft failure and eventual loss. Vascular outflow obstruction may be due to graft malposition. We describe our experience with liver allograft repositioning using tissue expander and Foley catheter to improve hepatic and portal venous outflows. PATIENTS AND METHODS: A total of seven patients who received liver transplantation at our institution developed hepatic and/or portal venous obstruction during final graft positioning detected by Doppler ultrasonography (hepatic vein flow <10 cm/s; portal vein flow <12 cm/s). Chart and operative records of these patients were reviewed. Technique of operation, donor-recipient characteristics, use of tissue expander or Foley catheter to improve venous outflow, complications, and outcome were analyzed. RESULTS: Hepatic and/or portal venous obstruction were detected after portal reperfusion. We used commercially available tissue expander used in plastic surgery and Foley catheter to reposition the graft. Tissue expanders were used in three recipients (age: 27-46 yr). Foley catheters were used in four recipients (age: 7 months-53 yr). One recipient used both tissue expander and Foley catheter. Expanders were filled with 300-770 mL saline and placed into the right subphrenic space. Foley catheters were filled with 15-75 mL saline. Significant improvements in hepatic and/or portal venous outflow were detected by Doppler ultrasonography post-graft repositioning. Aspiration of expander and Foley catheter contents was started from 6th to 27th postoperative day under sonographic guidance. All expanders and catheters were removed by the 19th-56th postoperative day (mean: 38 d). Complications included chylous ascites (1/7), bile leak (1/7), tube drain infection (2/7), septicemia (2/7). All complications were successfully managed by non-operative interventions. There was no outflow obstruction detected by ultrasonography before and after removal of expanders and catheters. One- and two-year graft and patient survivals were both 100%. CONCLUSION: The use of tissue expanders and Foley catheters to improve hepatic and portal venous outflow in malposed liver allografts is a simple and safe method after liver transplantation.     

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.     

Long-term hyperalimentation in children through saphenous central venous catheterization

During a 3.5 year period, 151 Silastic central venous catheters were inserted into the inferior vena cava through the saphenous vein in 132 children younger than age 19 years at UCLA Hospital. The major indications for catheter insertion included inflammatory bowel disease, cancer or bone marrow transplantation, and short bowel syndrome. The 151 catheters were used for a total of 13,288 days of fluid administration (mean 88 days). Complications requiring removal of the catheter occurred in 31 patients, but there were no deaths attributable to complications from the catheters. The total incidence of complications was one per 225 days of catheter use, less than that occurring in catheters placed in the external jugular and cephalic veins in young children in our hospital. The ease of insertion, the low complication rate and the simplicity of patient management when catheters are placed into the vena cava through the saphenous vein appear to make this an optimal site for administering parenteral nutrition in infants and children.     

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.     

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.     

原发性肝癌切除术后复发的肝移植治疗

目的总结原发性肝癌切除术后复发行肝移植治疗的经验。方法2002年8月至2004年11月上海交通大学医学院附属瑞金医院对4例肝癌切除术后复发病例（其中1例合并急性肝功能衰竭）行同种异体肝移植治疗。结果3例移植术后已分别无瘤存活17个月、12个月和27个月至今。1例术后第3天死于多器官功能衰竭。结论对原发性肝癌切除术后复发病例的肝移植治疗，小肝癌切除后复发肿瘤仍符合Milan标准者有着良好的预后；个别合并门静脉癌栓者预后较好；合并急性肝功能衰竭者应相当谨慎。     

肝移植治疗肝硬化门静脉高压症的临床疗效

目的 探讨肝移植治疗肝硬化门静脉高压症的临床疗效.方法 回顾性分析2000年1月至2012年1月北京大学人民医院收治的181例肝硬化门静脉高压症患者的临床资料.肝移植手术适应证为反复发作上消化道大出血,经内、外科和介入治疗无效,或合并肝功能失代偿的门静脉高压症患者.根据患者情况选择行经典原位肝移植或背驼式肝移植.术中于移植肝植入前后分别经胃网膜右血管置入套管针,连接测压管测压.观察手术前后门静脉压力变化情况,术后并发症的发生情况.术后通过肝移植随访中心定期随访,并根据具体指标调整用药,随访时间截至2012年12月,监测患者食管静脉曲张再出血及生存情况.Kaplan-Meier法计算生存率,计量资料采用（x）±s表示,均值比较采用t检验.结果 181例患者中,65例行经典原位肝移植,116例行背驮式肝移植.手术时间为（485±97） min,术中出血量为（4 380±1 993） mL,无肝期时间为（56±24） min.157例患者留置T管,24例患者未留置T管.102例患者术中经胃网膜右静脉测量了肝移植前后的门静脉压力,术前门静脉压力为（32±11）cmH2O（1 cmH2O =0.098 kPa）,术后门静脉压力为（21±6）cmH20,手术前后门静脉压力比较,差异有统计学意义（t=2.412,P＜0.05）.肝移植术后严重感染23例、急性肾衰竭20例、严重腹腔内出血6例、血管相关并发症5例和移植物原发无功能2例.181例患者均获得随访,随访时间为6 ～131个月.138例患者术后1年复查内镜或行上消化道造影检查,112例曲张静脉完全消失,其余26例较术前明显减轻,总改善率为85.71％（138/161）.术后1年内4例患者出现了上消化道再出血,再出血率为3.70％（4/108）,其中3例经止血药物或内镜治疗后得到缓解,1例死于再次出血导致的肝衰竭.随访患者术后1个月、1年及5年生存率分别为86.8％、84.9％、77.4％.23例死亡患者中,15例死于MODS,5例死?     

门静脉动脉化在肝脏外科的应用

门静脉动脉化是一种为防止肝脏缺血导致的肝损害而将动脉血灌注入门静脉的方法.本文就其在肝移植、肝门部肿瘤和门脉高压症外科治疗、急性肝功能衰竭治疗中的临床应用情况及存在的问题做一综述.     

Reversal of portal flow after acute rejection in living-donor liver transplantation

Portal hepatofugal flow is rare after liver transplantation. We experienced a case in which hepatofugal portal flow was observed in acute rejection. A 6-year-old boy with glycogen storage disease type Ia underwent living-donor liver transplantation. On postoperative day 7, portal venous peak velocity was markedly decreased without portal thrombosis and obstruction of the hepatic vein, and hepatic arterial peak velocity increased reciprocally. Based on a diagnosis of acute rejection, made on postoperative day 8, we initiated steroid pulse therapy. Despite the employment of this therapy, continuous hepatofugal portal flow was observed in the entire liver on postoperative day 8. On day 12, as the liver disorder progressed, the Doppler waveform in the portal vein changed from continuous to pulsatile hepatofugal flow. The patient died of liver failure on day 14. The histological findings of a biopsy specimen on day 9 showed centrilobular necrosis, while total hepatocellular necrosis was seen at autopsy. Hepatofugal flow after liver transplantation is considered to be an ominous sign caused by several factors, and its appearance indicates a fatal condition. Received: December 22, 2000 / Accepted: September 26, 2001     

Liver Ischemia Contributes to Early Islet Failure Following Intraportal Transplantation: Benefits of Liver Ischemic-Preconditioning

Early graft failure following intraportal islet transplantation (IPIT) represents a major obstacle for successful islet transplantation. Here, we examined the role of islet emboli in the induction of early graft failure and utilized a strategy of ischemic-preconditioning (IP) to prevent early islet destruction in a model of syngeneic IPIT in STZ-induced diabetic mice. Numerous focal areas of liver necrosis associated with the islet emboli were observed within 24 h post-IPIT. Pro-inflammatory cytokines, IL-1beta and IL-6, were significantly increased 3 h after IPIT, while TNF-alpha was elevated for up to 5 days post-IPIT. Caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells were observed in the transplanted islets trapped in areas of necrotic liver at 3 h and 1 day post-IPIT. Hyperglycemia was corrected immediately following IPIT of 200 islets, but recurrence of hyperglycemia was observed within 14 days associated with a poor response to glucose challenge. IP, a procedure of pre-exposure of the liver to transient ischemia and reperfusion, protected the liver from embolism-induced ischemic injury and prevented early islet graft failure. These data suggest that islet embolism in the portal vein is a major cause of functional loss following IPIT that can be prevented by liver IP.     

No‐Touch Hepatic Hilum Technique to Treat Early Portal Vein Thrombosis After Pediatric Liver Transplantation

A ‘no‐touch’ hilum technique used to treat early portal vein complications post‐liver transplantation in five children with body weight <10 kg is described. Four patients developed thrombosis and one portal flow absence secondary to collateral steal flow. A vascular sheath was placed through the previous laparotomy in the ileocolic vein (n = 2), inferior mesenteric vein (n = 1) or graft umbilical vein (n = 1). Portal clots were mechanically fragmented with balloon angioplasty. In addition, coil embolization of competitive collaterals (n = 3) and stent placement (n = 1) were performed. The catheter was left in place and exteriorized through the wound (n = 2) or a different transabdominal wall puncture (n = 3). A continuous transcatheter perfusion of heparin was subsequently administered. One patient developed recurrent thrombosis 24 h later which was resolved with the same technique. Catheters were removed surgically after a mean of 10.6 days. All patients presented portal vein patency at the end of follow‐up. Three patients are alive after 5 months, 1.5 and 3.5 years, respectively; one patient required retransplantation 18 days postprocedure and the remaining patient died of adenovirus infection 2 months postprocedure. In conclusion, treatment of early portal vein complications following pediatric liver transplantation with this novel technique is feasible and effective.