History Of Orthotopic Liver Transplantation Research Articles

S3212 Very Late Hepatic Artery Thrombosis After Orthotopic Liver Transplantation

Introduction: Hepatic artery thrombosis (HAT) is a serious complication after orthotopic liver transplantation (OLT) and is the most common vascular complication. It is often categorized into early HAT which is defined as occurring < 30 days after liver transplantation & late HAT defined as occurring > 30 days post transplantation. The etiology of HAT is often related to surgical factors, such as vessel kinking, anastomotic stenosis, and intimal dissection, but can factors such as hypercoagulability, elderly donors, and rejection episodes can contribute. Symptoms can often be vague with common complaints being abdominal pain, fever, nausea, & emesis. Case Description/Methods: A 68-year-old male with OLT (20 years prior to presentation) for primary sclerosing cholangitis (PSC), ulcerative colitis presented with 1 month history of nausea, emesis, and weakness. He was afebrile & hemodynamically stable. On physical exam, abdomen was soft, nontender, nondistended, and patient was jaundice. Laboratory data was notable for a two-month elevation of alkaline phosphatase, ALT, AST, direct bilirubin. An ultrasound of the liver with doppler evaluation was obtained that demonstrated an absence of flow in the left and right hepatic arteries within the liver. A computed tomography angiography (CTA) of the abdomen was obtained that confirmed these findings (Figure 1). Due to the history of PSC, a magnetic resonance cholangiopancreatography was obtained that showed no biliary dilation or evidence of recurrent PSC. A liver biopsy demonstrated paucicellular ductopenia with cholestasis consistent with chronic arterial insufficiency and no significant fibrosis. Transplant surgery and interventional radiology were consulted for potential recanalization. However, due to prolonged elevations in liver enzymes >4 weeks, both teams determined that recanalization would likely provide no benefit yet held greater risk. Discussion: This case highlights an uncommon, very late presentation of HAT. In the literature, late HAT has been described in the order of months, not years as it was in this case. It is usually associated with a less fulminant presentation and a milder course, in comparison to cases of HAT that present earlier in the post-transplant course. This case highlights the importance of considering HAT as a diagnosis in a patient with history of OLT who presents with abdominal pain, nausea, and emesis.Figure 1.: Focal filling defect in the hepatic artery seen in this venous phase CTA.

Transcatheter arterial embolisation of a haemorrhagic renal cyst

An 86-year-old woman with a history of orthotopic liver transplantation from non-alcoholic steatohepatitis, stage 4 chronic kidney disease secondary to calcineurin inhibitor toxicity and paroxysmal atrial fibrillation on apixaban presented...

Low Sensitivity to Thrombomodulin Correlates with Liver Stiffness in Advanced Chronic Liver Disease

Advanced chronic liver disease (ACLD) is characterized by changes in the coagulation system that embrace not only hypo-, but also hyper-coagulability. Global hemostatic tests such as thrombin generation (TG) assays are used to evaluate the hemostatic balance, in order to better assess bleeding and thrombotic risks. In addition, procoagulant state in ACLD patients has been demonstrated using modified TG assays with thrombomodulin (TM), a cofactor for protein C activation. Evaluation of the liver stiffness by transient elastography (Fibroscan) is a reliable method for the diagnosis of cirrhosis and disease staging. Increased liver stiffness is associated with clinically significant portal hypertension (PVT) in patients with ACLD. Here, we aimed to investigate whether TG parameters in patients with ACLD could be associated to liver stiffness. Of 147 enrolled patients with ACLD, we excluded 69 patients (5 patients received anticoagulation, 3 were on chemotherapy, 48 with other liver diseases and 13 had a history of orthotopic liver transplantation), leaving a study sample of 78 patients. Liver stiffness measurement (LSM) was performed by transient elastography in each patient. Cut-offs of 13 and 21 kPa were used to subgroup the studied ACLD patients sample, as a LSM of ≥13 kPa has been associated with the diagnosis of cirrhosis and ≥21 kPa with the development of a clinically significant PVT (Deillon et al., 2019). TG was evaluated by ST Genesia® Thrombin Generation System (STG) using Thromboscreen with/without TM (TS-TM/+TM) assay and the Calibrated Automated Thrombography (CAT) using PPP reagent low (Stago) with/without TM. TG was measured by STG in 50 patients with ACLD. ETP inhibition by TM correlated with LSM (r =-0.339, p=0.0184). The discriminant analysis (ANOVA with multiple comparison) among the study groups showed that ETP inhibition by TM was higher in ACLD patients with LSM &lt;13 kPa than in those with LSM ≥13 but &lt;21 kPa (p=0.003), indicating a lower sensitivity to TM in patients with liver stiffness values ≥13 but &lt;21 kPa. However, there was no difference in ETP inhibition by TM between the group with LSM ≥13 but &lt;21 kPa and the group with LSM ≥21 kPa (p=0.995). TG was measured by CAT in 56 patients with ACLD and ETP inhibition by TM was evaluated using a normalized ETP ratio in presence and in absence of TM. Similarly to STG data, ETP inhibition by TM measured by CAT correlated with LSM (r=0.4108, p=0.0018). The discriminant analysis among the study groups revealed that ETP inhibition by TM was higher in ACLD patients with LSM &lt;13 kPa than in those with ≥13 but &lt;21 kPa (p=0.0098) as well as with the group with LSM ≥21kPa (p=0.0022), indicating a lower sensitivity to TM in patients with liver stiffness values ≥13 kPa. However, there was no difference in ETP inhibition by TM between the group with LSM ≥13 but &lt;21 and the group with LSM ≥21 kPa (p=0.721). In addition, TG was measured by both by STG and CAT in 35 patients with ACLD in order to compare the two methods. ETP inhibition by TM measured by STG correlated with the normalized ETP inhibition determined by CAT (r = -0.61, p&lt;0.0001). Low sensitivity to TM measured in ST Genesia® and CAT, correlated with liver stiffness in patients with ACLD. Sensitivity to TM discriminated between ACLD groups with low (≤13 kPa) and high (≥13 kPa) LSM, confirming a procoagulant state in patients with ALCD. However, it did not differ between patients with ACLD with high LSM (≥13 and &lt;21 kPa) and patients prone to the decompensation defined by higher (≥21 kPa) LSM. Sensitivity to TM measurements determined by ST Genesia® correlated with those obtained with CAT. Further studies are needed to determine whether sensitivity to TM and LSM in patients with ACLD could help to identify patients at higher risk of portal vein thrombosis Disclosures No relevant conflicts of interest to declare.

2299 Resolution of Acute Cellular Rejection Using Irradiating Packed Red Blood Cells for Exchange Transfusion in a Patient With Sickle Cell Disease and a History of Orthotopic Liver Transplantation

INTRODUCTION: Liver transplantation in patients with Sickle Cell Disease (SCD) is fairly unique; a review article from 2013 noted only 15 reported cases within the literature. This case highlights a patient with SCD who underwent orthotopic liver transplantation. His course was complicated by iron overload due to recurrent exchange transfusions, as well as biopsy-proven acute cellular rejection (ACR), that was inadequately treated with corticosteroids, with no recurrence of rejection once the patient was switched to irradiated red cell exchange transfusions. CASE DESCRIPTION/METHODS: A 32-year-old male with HbSS disease, who had also undergone orthotopic liver transplantation at the age of 26 due to complications of Caroli’s disease presented with persistent abnormal liver tests over the course of several weeks. Graft function was normal during post-transplant until monthly exchange transfusions were initiated to manage his sickle cell crises. During this period he had two episodes of ACR and was noted to have persistent liver test abnormalities despite adequate therapeutic levels of tacrolimus. The patient was switched to receiving irradiated packed red blood cells for his subsequent exchange transfusions, which led to improvement of his liver tests and resolution of his acute cellular rejection. DISCUSSION: Only a limited number of patients with sickle cell disease have undergone liver transplantation, and this is the first case of using irradiated packed red cells for transfusion to help resolve acute cellular rejection. Although it is not thoroughly understood how blood transfusions could induce acute cellular rejection, it may be related to passenger donor leukocytes within the donor blood products triggering an immune response within the transplanted liver. Given our patient’s exposure to higher volumes of transfusions, there may have been enough donor lymphocytes to trigger this response. The use of irradiated blood products is common place in patients that have received hematopoietic stem cell transplants. Current recommendations do not standardize use of irradiated red cells for solid organ transplant (SOT) recipients. Our patient presents an unusual indication for use of irradiated red cells in a SOT patient.

Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report

Tacrolimus, also known as FK-506, is a potent immunosuppressant agent with a host of drug-drug and food-drug interactions. We present the first case of a probable food-drug interaction between the herb turmeric and tacrolimus leading to acute calcineurin inhibitor nephrotoxicity. A 56-year-old man with a history of orthotopic liver transplantation presented to the emergency department from the clinic with worsening edema in the setting of an elevated creatinine level of 4.2 mg/dL. Before the current presentation, the patient had been recently discharged on a previously tolerated low-dose regimen of tacrolimus with a whole-blood tacrolimus level within the desired range. Tacrolimus level on the day of re-hospitalization was elevated to 29.9 ng/mL in the absence of any changes to the patient's medication regimen. On further prompting, the patient identified recent high-dose intake of turmeric with his food. Tacrolimus was held from the patient's medication regimen, and he was discharged on hospital day 4 with objective evidence of improving renal function. Our report builds on the previous studies that described the effects of turmeric or its active ingredient on the pharmacokinetics of tacrolimus. The appropriate reconciliation of herbal agents such as turmeric can be worthwhile in patients with unexplained changes in tacrolimus levels.

Methicillin-Resistant Staphylococcus aureus Prostatic Abscess in a Liver Transplant Recipient.

Prostatic abscesses are usually related to gram-negative bacilli. However, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a substantial cause of prostatic abscesses in recent years. Herein, we report the case of a 31-year-old man with a history of orthotopic liver transplantation 10 years ago who presented with acute onset dysuria and abdominal pain and was diagnosed with a MRSA prostatic abscess. To our knowledge, this is the first case describing a prostatic abscess in a liver transplant recipient and the first reporting MRSA as the causative organism of a prostatic abscess in a solid organ transplant recipient.

An Unusual Cause of Cholestasis After Liver Transplantation

Question: A 57-year-old Caucasian man with history of orthotopic liver transplantation for cryptogenic cirrhosis (5 years before admission) and kidney transplantation for focal segmental glomerulosclerosis (3 years before admission) presented to our institution with sudden onset chest pain. His posttransplant course was unremarkable. Other medical history includes a history of myocardial infarction necessitating stent placement, diabetes mellitus, and hypertension. In the emergency department, his blood pressure was 130/62 mmHg and pulse rate 76 bpm.

Graft-Versus-Host Disease (GVHD): A Rare but Lethal Cause of Common Gastrointestinal Symptoms Following Orthotopic Liver Transplantation (OLT)

Purpose: 1) To increase awareness of GVHD as an uncommon but life-threatening etiology of common gastrointestinal symptoms after OLT. 2) To highlight the role of histopathology in augmenting endoscopy as a powerful diagnostic tool. Case: A 45-year-old male with a history of OLT four months earlier for alpha-1 antitrypsin deficiency was admitted to hospital with two days of diarrhea, abdominal pain and vomiting. He was febrile, tachycardic and jaundiced with a benign abdominal exam. Laboratory tests showed pancytopenia, acute renal insufficiency, hyperbilirubinemia and positive stool Clostridium difficile (C. diff.) toxin. Computed tomogram showed diffuse small bowel wall thickening. Treatment for C. diff. infection was initiated. Mycophenolate was discontinued and he was maintained on tacrolimus. He continued to clinically deteriorate and have high stool output despite aggressive treatment of C. diff. infection. Flexible sigmoidoscopy showed pseudomembranous colitis but colon biopsies were non-diagnostic. His course was further complicated by pneumonia, bacteremia, coagulopathy, dialysis-dependent renal failure and upper gastrointestinal bleed. Esophagogastroduo-denoscopy (EGD) showed gastric erythema and friability consistent with possible stress gastritis and normal duodenum. Biopsies were not taken. Due to clinical deterioration, the patient underwent colectomy. Histopathology of the colon revealed possible GVHD. Intraoperative liver biopsy showed cholestasis only. Repeat upper endoscopy to establish the diagnosis showed severely denuded mucosa in the stomach and duodenum. Gastric and small bowel biopsies confirmed GVHD. He was treated with high-dose corticosteroids and extracorporeal plasmapheresis, complicated by line-related sepsis. Treatment was discontinued. The patient expired 45 days following admission. Discussion: Although GVHD is commonly associated with bone marrow transplantation (BMT), it is a rare and life-threatening complication of OLT with an incidence of 0.1% to 2%. The risk is significantly increased when the recipient and donor share a major histocompatibility antigen haplotype. The liver allograft is always spared. The diagnosis is often delayed because other common OLT complications, such as infection, can present with a similar clinical picture. Most experience for treatment of GVHD comes from BMT. However, these therapies have been disappointing in the setting of GVHD after OLT. Conclusions: GVHD is a rare but serious complication of OLT with limited treatment options. High clinical suspicion and obtaining biopsies for histopathologic diagnosis augments the diagnostic yield of endoscopy, particularly in challenging cases that defy usual diagnosis.

Successful unrelated donor stem cell transplantation for advanced myelofibrosis in an adult patient with history of orthotopic liver transplantation

Patriarca et al.1 recently reported a significant improvement in outcome of patients with myelofibrosis (MF) after allogeneic stem cell transplantation (SCT). Some MF patients present to the transplant center with severe complications after a long disease history and their treatment may be very challenging. In 1987, a 33-year old woman was diagnosed with polycythemia vera (PV) associated with portal and splenic vein thrombosis. A year later she developed acute Budd-Chiari syndrome and required orthotopic liver transplantation. In 2002, 15 years since diagnosis, PV progressed to MF. Molecular genetics revealed heterozygous V617F mutation in the Janus Kinase 2 (JAK 2) gene. In 2006, blood count showed: leukocytes 1.5 × 109/L, hemoglobin 8.1 g/dL, platelets 124 × 109/L and 13% circulating blasts. Blood transfusions were required every eight weeks. According to the Lille Scoring System the patient was at high risk of progression to acute leukemia. Since she had no siblings, we decided to start an unrelated donor search, although very few reports exist on allogeneic SCT in patients after preceding solid organ, respectively liver, transplantation. A compatible donor with a single human leukocyte antigen (HLA) Cw mismatch was identified. Patient and donor were mismatched for blood group and cytomegalovirus serology. In April 2007 allogeneic SCT following treosulfan (30 g/m2), fludarabine (150 mg/m2) and anti-thymocyte globuline (ATG 30 mg/kg, Fresenius Biotech, Germany) conditioning was performed. Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine A and mycophenolate mofetil. Engraftment was achieved rapidly. The first 100 days after SCT were complicated by an asymptomatic CMV reactivation and probable viral encephalitis with lymphocytic pleocytosis in spinal fluid and meningeal MRI enhancement but without positive virology findings. Both episodes were successfully treated with foscarnet. As a further complication, syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurred. Acute GVHD or veno-occlusive disease (VOD) did not occur and liver function remained stable. From day 100 onwards, polymerase chain reactions (PCR) of peripheral blood samples were negative for the JAK2 gene mutation consistent with complete molecular remission of MF. Also sustained complete donor chimerism was confirmed by molecular studies. Bone marrow biopsy at day 100 showed a normal hematopoiesis without signs of fibrosis. Imunosuppression was reduced but the patient remained on low-dose cyclosporine A and prednisone as prior to SCT. A biopsy proven chronic scleroderma GvHD of the skin developed eight months after SCT and mycophenolate mofetil was re-started. Sicca symptoms, persistant cachexy and senso-motoric polyneuropathy developed in the following few months. Eighteen months after SCT the blood count showed: leukocytes 4.0/nL, hemoglobin 13.7 g/dL, platelets 112 × 109/L. In MF allogeneic SCT is the only treatment modality with the potential to provide prolonged disease control or even cure, whereas conventional treatment results are usually disappointing. Recent reports showed hematologic response in up to 100% and complete histopathological remission in 75% of patients with MF who underwent allogeneic SCT.2,3 High rates of molecular remission are achievable in JAK2-positive patients.4 The feasibility of allogeneic bone marrow transplantation (BMT) from a sibling donor following cadaveric liver transplantation has been demonstrated in a pediatric patient with severe aplastic anemia (SAA) following non-A, non-B, non-C (NANBNC) hepatitis.5 Also long-term follow-up after sibling donor BMT for SAA following orthotopic liver transplantation for hepatitis was reported in another pediatric patient.6 Combined cord blood and haplo-identical BMT for SAA after living-related liver transplantation from the same donor was proposed as an option for children with liver failure due to diseases that can be cured by allogeneic SCT.7 A single case of an adult 29-year old patient with SAA, who received myeloablative conditioning for sibling allogeneic BMT four months after orthotopic liver transplantation for NANBNC hepatitis, has been reported.8,9 Severe acute GvHD of the liver was not observed in any of these cases.5–8 It has been suggested by studies in mice and humans that the liver is the most capable of inducing tolerance after solid organ transplantation due to high leukocyte content, particularly due to the antigen-presenting dendritic cells and their progenitors that migrate from the liver into peripheral blood and tissues, modulate immune responsiveness and induce immunological tolerance.10 In this case we could not detect liver-donor derived leukocyte microchimerism for technical reasons after cadaveric liver transplantation. We postulate that microchimerism after solid organ transplantation might facilitate engraftment and prevent GvHD, but further studies are necessary in this field. To our knowledge this is the first report of a successful reduced intensity conditioning allogeneic SCT from an unrelated donor in an adult patient with a history of liver transplantation. This case might encourage physicians to propose allogeneic SCT to patients with hematologic diseases, who had previous liver or other solid organ transplantations.

Successful Diagnosis and Management of Biliary Cast Syndrome in a Liver Transplant Patient Using Single Operator Cholangioscopy

Purpose: Biliary cast syndrome is an unusual complication of orthotopic liver transplantation (OLT) with serious clinical implications. Biliary cast formation is usually associated with biliary strictures and/or hepatic ischemia. Surgical management is the mainstay of treatment. Endoscopic techniques have been recently described in the successful removal of biliary casts. We report a post OLT patient who underwent successful endoscopic removal of biliary cast using single operator cholangioscopy. Our patient is a 68 year-old male with history of OLT seven months before for hepatitis C induced cirrhosis who came for a follow up visit. He had no complaints and physical exam was normal. He had cholestatic liver enzyme elevation (Alkaline phosphatase 580 IU/L, Total bilirubin 2.3 mg/dl) with normal aminotransferases. Hepatitis C RNA was undetectable. Ultrasound demonstrated normal common bile duct (CBD) diameter with normal Doppler flow. Liver biopsy showed no rejection with suggestion of cholestasis. Endoscopic retrograde cholangiopancreatoscopy (ERCP) was performed and cholangiogram showed multiple linear filling defects in the common hepatic duct (CHD) proximal to the anastomosis with extension into the intrahepatic system. After failure of the balloon to remove the filling defect, a single-operator choledochoscope was passed into the CHD for diagnostic and possible therapeutic purposes. A dark brown tubular structure was seen resembling a cast of the bile duct. Using a basket, the distal aspect of the cast was secured and a 6 cm long cast was successfully removed in a single piece. (Image) Cholangiogram showed improvement with excellent biliary drainage both fluoroscopically and endoscopically. Liver function tests have subsequently normalized and the patient remains normal with a follow period of 10 months without recurrence. In conclusion, Biliary cast syndrome is a rare complication of OLT which should be thought of when patients present with cholestatic liver enzyme elevation usually within the first year of transplant. Single operator cholangioscopy provides a safe means of diagnosing and treating patients with Biliary cast syndrome particularly in cases with intrahepatic duct casts where surgery or percutaneous techniques are often required. Methods: N/A Results: N/A Conclusion: N/A

Progressive pulmonary calcification in a child after orthotopic liver transplantation

We present a case of progressive pulmonary calcification associated with prolonged respiratory insufficiency in a 2-year-old boy with a history of orthotopic liver transplantation. This case demonstrates the potentially progressive nature of pulmonary calcification and that it can present with respiratory insufficiency at a later period after transplantation than previously thought. We describe radiological findings and discuss established as well as plausible pathological mechanisms contributing to the development of calcifications in these patients.

Blood cyst of the mitral valve apparatus in a woman with a history of orthotopic liver transplantation

Blood cysts within the heart are rare findings in adults. We describe a case of a woman with a history of orthotopic liver transplantation who presented for an echocardiogram to evaluate a potential source of cerebrovascular embolism. A cystic mass attached to the submitral valve apparatus was identified by transthoracic and confirmed by transesophageal echocardiography. Surgical exploration and pathologic examination confirmed the mass to be a blood cyst attached to the chordal apparatus of the posterior papillary muscle. This case report highlights the use of echocardiography in diagnosing intracardiac blood cysts.