Acute Hepatic Artery Thrombosis Research Articles

S3145 Severe Transplantation-Mediated Alloimmune Thrombocytopenia After Liver Transplant Treated Successfully With Efgartigimod

Introduction: Transplantation-mediated alloimmune thrombocytopenia (TMAT) is a rare form of passenger lymphocyte syndrome in which lymphocytes from the donor organ produce antibodies against recipient platelets resulting in thrombocytopenia. We describe a novel treatment of TMAT with efgartigimod, a human IgG1 Fc antibody fragment, in a patient with severe, refractory thrombocytopenia following liver transplantation. Case Description/Methods: A 70-year-old man with cirrhosis secondary to non-alcoholic steatohepatitis complicated by hepatocellular carcinoma underwent deceased donor orthotopic liver transplantation. He required emergent retransplantation on post-operative day 7 for acute hepatic artery thrombosis. Seven days after retransplantation, the patient developed severe thrombocytopenia with platelets <1 × 109/L. He responded poorly to platelet transfusion, and two days later developed severe intra-abdominal bleeding requiring exploratory laparotomy. No active bleeding was found, and splenectomy was performed. Testing for heparin induced thrombocytopenia was negative, and the working diagnoses were post transfusion purpura and idiopathic thrombocytopenic purpura. Over the next 8 weeks, the patient had persistent, severe thrombocytopenia despite platelet transfusions and treatment with intravenous immunoglobulin, plasmapheresis, rituximab, romiplostim, and eltrombopag. Notably, two patients who received lung and kidney transplants from the same donor also developed severe thrombocytopenia. Ultimately, testing revealed the presence of serum antibodies to human platelet antigen (HPA) 1a. Genetic testing revealed the genotypes HPA 1a/1b and HPA 1b/1b in the patient and donor respectively, consistent with a mismatch and TMAT. The patient received weekly efgartigimod for 4 doses, and after his third infusion developed sustained improvement in platelets to >100 × 109/L without need for transfusion. Discussion: TMAT is a rare disorder after solid organ transplantation that can lead to severe thrombocytopenia with life threatening bleeding and even death. Although TMAT generally resolves a few months after transplantation as donor lymphocytes are cleared from the circulation, initial management is challenging. Efgartigimod is a novel treatment approved by the food and drug administration for myasthenia gravis that leads to degradation of IgG by binding to the neonatal Fc receptor and should be considered for severe TMAT.

Experience With Donors With Positive Serology for Chagas Disease in Liver Transplantation.

Introduction: Utilization of marginal donors in liver transplant (LTx) has been one of the options to increase the availability of grafts. Incidence of donors with positive serology for Chagas has varied from 0,4 to 1,1% of the donors pool in Brazil. Despite the possibility of disease transmission to recipients, our policy has been to utilize these grafts in hepatocellular carcinoma (HCC) or in urgent clinical conditions. Purpose: To analyze the results of LTx using donors with positive serology for Chagas. Methods and patients: From Sept/1997 to Dec/2013, 5 grafts with positive serology for Chagas disease were transplanted into 5 recipients with negative serology for that disease. Donors and recipients demographic date, waiting time on list (WTL), LTx indicators, patient survival and Chagas disease transmission incidence were analyzed. Serologies for Chagas were collected every 15 days in the first 3 months following the LTx, and monthly after for one year, or if recipients showed any symptom of acute Chagas disease. Results: All 5 recipients were male, age and weight ranging from 44-59 yrs and 74-86 kg, respectively, and WTL (days): 20 -1006. Donors age ranged from 48-72yrs, TGP: 13-69(U/L), Sodium: 142 -170 mMol/L, days on UTI: 3-8. All patients underwent LTx due to cirrhosis and hepatocarcinoma, except for one patient who needed urgent LTx due to acute hepatic artery thrombosis. One patient presented acute Chagas disease 6 months after LTx with good evolution after clinical treatment. 3 patients died after LTx; 1 due to bacterian meningitis (following use of OKT3 for treating steroid-resistant acute rejection) and 2 due to HCC recurrence at 22 and 48 months. The other 2 patients are alive at 9 and 10 years after LTx. Conclusion: Despite the small number of cases (n=5) of LTx using grafts with positive serology for Chagas disease, only 1 patient developed acute Chagas disease with good evolution after clinical treatment. From these still incipient results, our recommendation is that these grafts don't be automatically discarded and be destined preferably to recipients with tumors or in urgent LTx.

Minimally invasive endovascular and biliary treatments of children with acute hepatic artery thrombosis following liver transplantation

Hepatic artery thrombosis is a major problem after pediatric liver transplantation. Ischemia caused by hepatic artery thrombosis results in severe biliary and parenchymal damage and is associated with high rates of graft loss and mortality. We present a case-based pictorial essay to illustrate the role of minimally invasive treatment in the prompt management of acute hepatic artery thrombosis, and the associated biliary complications.

Percutaneous Endovascular Treatment of Hepatic Artery Stenosis in Adult and Pediatric Patients After Liver Transplantation

The purpose of this study was to evaluate the efficacy of percutaneous endovascular techniques for the treatment of hepatic artery stenosis (HAS) occurring after liver transplantation (LT) in adult and pediatrics patients. From February 2003 to March 2009, 25 patients (15 adults and 10 children) whose developed HAS after LT were referred to our interventional radiology unit. Technical success was achieved in 96% (24 of 25) of patients. Percutaneous transluminal angioplasty (PTA) was performed in 13 patients (7 children), and stenting was performed in 11 patients (2 children). After the procedure, all patients were followed-up with liver function tests, Doppler ultrasound, and/or computed tomography. Mean follow-up was 15.8 months (range 5 days to 58 months). Acute hepatic artery thrombosis occurred immediately after stent deployment in 2 patients and was successfully treated with local thrombolysis. One patient developed severe HA spasm, which reverted after 24 h. After the procedure, mean trans-stenotic pressure gradient decreased from 30.5 to 6.2 mmHg. Kaplan-Meyer curve of HA primary patency was 77% at 1 and 2 years. During the follow-up period, 5 patients (20%) had recurrent stenosis, and 2 patients (8.3%) had late thrombosis. Two of 7 patients with stenosis/thrombosis underwent surgical revascularization (n = 1) and liver retransplantation (n = 1). Six (25%) patients died during follow-up, but overall mortality was not significantly different when comparing patients having patent hepatic arteries with those having recurrent stenosis/thrombosis. There were no significant differences in recurrent stenosis/thrombosis and mortality comparing patients treated by PTA versus stenting and comparing adult versus pediatric status. Percutaneous interventional treatment of HAS in LT recipients is safe and effective and decreases the need for surgical revascularization and liver retransplantation. However, the beneficial effects for survival are not clear, probably because the clinical complexity of many of these cases.

A single center experience of combined liver kidney transplantation

With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.

Intraarterial Thrombolytic Treatment for Hepatic Artery Thrombosis Immediately After Living Donor Liver Transplantation

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) remains one of the major causes of graft failure and mortality in liver transplant recipients. This complication requires early diagnosis and revascularization to avoid graft loss. We have reported herein two cases of successful urokinase intraarterial thrombolytic treatment for HAT in the immediate postoperative period after LDLT. Significant elevation of liver transaminases was noted 6 and 4 hours after LDLT and HAT confirmed by three-dimensional computed tomogram and angiogram. Both patients were treated successfully with intraarterial thrombolysis using an urokinase infusion (a total dose of 200,000 to 250,000 IU over 20 to 25 minutes) immediately after HAT was confirmed. One patient underwent laparotomy and bleeder ligation owing to hepatic arterial anastomotic site bleeding after thrombolysis. These two patients remain in good condition without any ischemic graft sequelae at 7 and 8 months follow-up. In conclusion, intraarterial thrombolysis using an urokinase infusion could be considered as one of the treatment modalities of acute HAT following LDLT even in the immediate postoperative period.

Pediatric Liver Transplantation: Preliminary Results at Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione

Between July 2003 and November 2004 14 pediatric liver transplantations (LTx) have been performed in 12 children using cadaveric donors. The primary diseases were as follows biliary atresia in 9 cases, whereas the other 3 children were affected by cystic fibrosis, Langherans cells histiocytosis, and hepatoblastoma, respectively. Median patient waiting time was 103 days (range, 2–158); no patient died while on the waiting list. Patients who underwent transplantation included 7 boys and 5 girls, ranging in age from 6 months to 14 years (median age, 5 years). Recipient median weight was 16 kg (range, 6–38). Donor median age was 19 years (range, 3–47), whereas donor median weight was 74 kg (range, 15–90). All children who underwent primary LTx were United Network for Organ Sharing (UNOS) status 2B. Of the 12 transplanted patients, 9 received a left lateral segment (LLS) from an in situ split liver, whereas 3 received a whole graft. Two children developed an episode of acute cellular rejection on the seventh postoperative day, which was treated successfully with a course of intravenous steroids for 3 days. After a median follow-up of 245 days, 10 children are alive but 2 children died due to primary nonfunction (PNF) on the second postoperative day and septic shock on the fifth postoperative day after retransplantation for acute hepatic artery thrombosis, respectively. One child who underwent retransplantation for hepatic artery thrombosis on the 31st postoperative day after primary LTx is currently alive. Evaluation of our initial data suggests that the split liver technique has the potential to meet the needs of pediatric LTx allowing grafting early in the course of the original disease and reducing waiting time.

Endoscopic management of the liver transplant patient

Endoscopic management of the liver transplant patient

Right lobe living related graft loss due to intrahepatic multiple arterio-portal fistulas

We report a case of a 38-year-old Caucasian female with ileal carcinoid and bilobar hepatic metastases. After resection of the primary tumor, octreotide therapy was prescribed. Carcinoid histology was positive for chromogranin A and sinaptophsine and negative for MIB1. At 1-year, a follow-up computed tomography scan, Octreoscan, and PET scan were negative for extrahepatic involvement. The patient underwent right lobe living related liver transplantation donated by her sister. Acute hepatic artery thrombosis was successfully revascularized 24 hours after transplantation. Extrahepatic biliary ischemia was treated by a bilio-digestive anastomosis. Eight months later, ascites and clinical and serologic signs of liver failure developed; a liver biopsy revealed fibrosis. Spiral computed tomography scan and hepatic angiography showed multiple intrahepatic arterio-portal fistulas resulting in arterialization and inversion of the portal flow in the absence of graft outflow obstruction.

Early postoperative complications in recipients of living donor liver transplantation

Purpose Complications are common in the early postoperative period after living donor liver transplantation (LDLT). The aims of this analysis were to describe and identify risk factors for early postoperative complications. Methods Between June 1994 and June 2003, 140 consecutive LDLT patients were divided into 3 groups: group I was small infants <9 kg (n = 30); group II, pediatric patients (n = 63); and group III, adult patients (n = 47). The complications within 3 months after operation were analyzed. Results The mortality rate was 1.4%. Surgical complications requiring relaparotomy occurred in 7.9% of patients. Intraoperative portal vein thrombosis requiring immediate thrombectomy, which occurred in 10 patients, was significantly more frequent in the small infant group (23.1% vs 3.2% vs 2.1%; P < .01). Acute hepatic artery thrombosis that occurred in 2 patients was remedied successfully using operative rearterilization. Hepatic outflow obstruction requiring radiological interventions developed in 5 subjects. Medical complications included the following: pulmonary (14.3%), renal (19.3%), bacteremia (10.7%), cytomegalovirus infection (9.3%), and drain-related infections (20.7%). The incidence of hospital-acquired renal insufficiency was significantly higher in adult patients (3.3% vs 14.3% vs 36.2%; P < .01). There was no significant difference in the incidence of acute cellular rejection between members of the 3 groups (10.0% vs 17.5% vs 17%; P = .63). Conclusions Sophisticated postoperative care with multiple disciplinary involvements may achieve a low early mortality rate in LDLT. Small infants weighing <9 kg may carry a greater risk of intraoperative portal vein thrombosis. Pulmonary complications and renal function impairments were the most troublesome in pediatric and adult recipients, respectively.

Liver transplantation with reduced-size donor organs.

Orthotopic liver transplantation (OLT) of the pediatric patient is often limited by the availability of a size-matched donor organ. Use of reduced liver transplantation (RLT) can increase the proportion of candidates transplanted and may reduce overall mortality. We report herein the initial clinical application of RLT in the United States. Indications for RLT included fulminant hepatic failure (n = 2), acute hepatic artery thrombosis (n = 3), and chronic liver disease unresponsive to inpatient support and more than 30 days on transplant list (n = 4). Donor hepatectomy was performed using standard techniques. Formal hepatic resection was performed ex-vivo to create a size-matched graft, from the larger donor organ, which was implanted in the orthotopic position. Between 11/84 and 4/87, 70 pediatric patients were evaluated for OLT, and 33 of these were transplanted. During this period only 5 patients (7%) died awaiting OLT. Of 33 patients treated at the University of Chicago, 5 received RLT. Donor: recipient weight ratios ranged from 2:1 to 8.1:1. For RLT median operative blood loss was 1.7 blood volumes (range 0.5-11.7) with an operative time of 9.3 + 3.5 hr. Acceptable early graft function was observed in five patients, all of whom were discharged from the hospital. Four of these five patients are alive between 2 and 48 months after transplantation. Marginal graft function with cholestasis and coagulopathy was associated with acute intracranial hemorrhage and neurologic death in one case. One patient died intraoperatively with non-function caused by the use of a liver from a donor with steatosis and a poor size match. Another patient died on day 5 with primary nonfunction and persistent hemorrhage. Systemic cytomegalovirus infection was the cause of death in the other two cases. RLT can provide life-sustaining liver function in urgent clinical settings. The graft can serve as a temporary or permanent liver replacement. With evolution of the technique RLT could eventually be offered to more elective candidates and increase the utilization of available donors by reducing size limitations in OLT.