Living-related Orthotopic Liver Transplantation Research Articles

Pulmonary hypertension and cardiac hypertrophy in children recipients of orthotopic living related liver transplantation

Surgical stress, liberation of cytokines associated with re-perfusion injury, and long standing use of immune suppressive medications in children recipients of orthotopic living related liver transplantation (OLRLT) pose cardiovascular risk. Reported cardiovascular adverse effects vary from left ventricular wall thickening, hypertrophic cardiomyopathy to resting ECG abnormalities, asymptomatic ST depression following increased heart rate and ventricular arrhythmias. Twenty-five consecutive children recipients of OLRLT were assessed by conventional 2-D, M-mode echocardiography and Doppler. The mean age±SD at transplantation and at enrollment in study was 6.3±4.5 and 13.5±5.6years respectively. All children were on immunosuppressive medications, with tacrolimus being constant among all. Long-term post-transplant echocardiography revealed statistically significant interventricular septal hypertrophy among all (mean thickness 0.89±0.16cm), (P=0.0001) in comparison to reference range for age, 24 had pulmonary hypertension (mean mPAP 36.43±5.60mmHg, P=0.0001), and early diastolic dysfunction with a mean Tei index of 0.40±0.10. However cardiac function was generally preserved. Children recipients of OLRLT have cardiac structural and functional abnormalities that can be asymptomatic. Pulmonary hypertension, increased cardiac mass, de novo aortic stenosis and diastolic heart failure were among abnormalities encountered in the studied population. Echocardiography is indispensible in follow-up of children recipients of OLRLT.

Successful treatment of mixed-type autoimmune hemolytic anemia with rituximab in a child following liver transplantation

Development of a severe form of mixed-type AIHA after orthotopic liver transplantation is a rare, but a life-threatening event. We report a case of mixed-type AIHA that developed in a child after hepatocyte and living-related orthotopic liver transplantation for factor VII deficiency.

Cytomegalovirus-associated Immune Thrombocytopenic Purpura After Liver Transplantation

Immune thrombocytopenic purpura (ITP) is a rare complication after liver transplantation. Infection with cytomegalovirus (CMV) is a frequent complication of organ transplantation and may induce autoimmune diseases, such as ITP. We report a case of ITP after primary CMV infection in a 3-year-old boy recipient of living-related orthotopic liver transplantation (OLT). The ITP developed 2 years after OLT in this patient who had received tacrolimus as an immunosuppressive agent, with nadir platelet counts of 5000/mm(3) in 2 weeks. The patient was treated with two courses of intravenous gamma globulin (1 g/kg/day for 2 days) and subsequent oral prednisolone (1.3 mg/kg/day for 2 weeks). He recovered from thrombocytopenia 4 weeks later. An inadequate immunosuppression, as evident by the low serum tacrolimus level (5.8 ng/mL before the episode of ITP) in this patient, may allow the development of ITP after CMV infection.

Accurate preoperative estimation of liver-graft volumetry using three-dimensional computed tomography.

The aim of this study was to clarify the value of three-dimensional computed-tomography (3D-CT) volumetry for size matching in living-donor liver transplantation (LDLT). 3D-CT volumetry was applied to 25 donors who underwent hepatectomy for a living relative needing an orthotopic liver transplantation. Fifteen patients underwent extended left lobectomy, one patient an extended left lateral lobectomy, and nine patients right lobectomy. 3D-CT imaging was performed with the workstation ZIO M900 (Zio Software Inc., Tokyo, Japan). The estimated volume of the grafts in two-dimensional (2D) and 3D images were compared, and an error ratio was calculated. 3D-CT imaging revealed the anatomy of the hepatic vein bifurcation and the shape of the graft. The error ratio was 12.8+/-2.3% in 3D, compared with 19.4+/-2.5% in 2D. As such, 3D-CT volumetry appears to be more exact than conventional 2D-CT volumetry, but volumetry by 3D-CT still produces an error ratio of approximately 13%. The weight transition of the rats' livers under preservation in University of Wisconsin (UW) solution indicated that the graft volume seems to decrease during perfusion with UW solution. Mismatch of the cutting line and volume reduction by dehydration (approximately 5% reduction 1 hour after perfusion) seems to cause the error in 3D-CT volumetry. Three-dimensional CT volumetry is useful for size matching in cases of living-related orthotopic liver transplantation.

The Impact of Liver Disease on Growth and Nutrition

The Impact of Liver Disease on Growth and Nutrition

Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: A case report

Kohzuki M, Abo T, Watanabe M, Goto Y, Ohkohchi N, Satomi S, Sato T. Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: a case report. Arch Phys Med Rehabil 2000;81:1527-30. The objective of this study was to rehabilitate a patient with hepatopulmonary syndrome (HPS) who underwent living-related orthotopic liver transplantation (LT). HPS is rare; it presents severe complication in patients with liver disease. A 17-year-old woman with HPS developed portal hypertension after undergoing Kasai's surgery for congenital biliary atresia and underwent a living-related orthotopic LT. After LT, her allograft functioned well, but she continued to have hypoxemia and orthodeoxia. She was referred for rehabilitation for disuse atrophy, contracture of hip and shoulder joints, left common peroneal nerve palsy, and rehabilitation for respiratory dysfunction. By day 106 after LT, her orthodeoxia and disuse atrophy had improved because of daily exercise training and active joint range of motion exercises. Patients with HPS have orthodeoxia and poor responsiveness to oxygen therapy, and correction of hypoxemia after LT may be delayed. Therefore, rehabilitation approaches for patients with HPS should be based on the pathophysiology and characteristics of HPS. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Cumulative experience with pediatric living related liver transplantation

Purpose: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. Methods: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. Results: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), α-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. Conclusion: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease. J Pediatr Surg 35:9-12. Copyright © 2000 by W.B. Saunders Company.

Cumulative experience with pediatric living related liver transplantation

This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), alpha-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease.

De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: Analysis by determining complete sequence of the genome

De novo infection of hepatitis B virus (HBV) occurs after liver transplantation from donors with HBV markers that suggest past infection. In the present study, the complete nucleotide sequences of HBV derived from a donor and recipients were determined to determine the clinical and virological characteristics. A total of 57 donor-recipient pairs, which underwent living-related orthotopic liver transplantation, were enrolled in the present study; all were negative for HBsAg before transplantation. HBV DNA was tested in serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) by the polymerase chain reaction (PCR). The nucleotide sequence of HBV was determined based on PCR products and the phylogenetic analysis. De novo infection of HBV was found in 3 of the 57 recipients. Anti-HBc was positive in all donors of 3 recipients with the de novo infection but was positive only in 4 donors of the remaining 54 recipients (P=0.001). HBV DNA was detected in the liver but not in the serum or PBMCs in donor 3 whose recipient developed de novo HBV infection. The nucleotide sequence covering entire genome of HBV (3,215 bases) derived from the liver of donor 3 had a homology of 99.8-100% with that derived from the serum of corresponding recipient 3. The strain of recipient 3 showed the closest association with that of the donor 3 by phylogenetic analysis. Complete sequences from two recipients with de novo HBV infection including recipient 3 conserved the basic organisation of HBV genome. Analysis of the entire nucleotide sequence of HBV genome proved that HBV existed in the liver of the donor with anti-HBc, and it caused de novo infection in the corresponding recipient.

Successful cytokine treatment of aplastic anemia following living-related orthotopic liver transplantation for non-A, non-B, non-C hepatitis

The relationship between aplastic anemia and viral hepatitis is well recognized, and such patients usually have a high mortality. We successfully treated a case of aplastic anemia following living-related orthotopic liver transplantation (LROLT) for non-A, non-B, non-C hepatitis. A 2-yr-old boy with fulminant hepatic failure from non-A, non-B, non-C hepatitis received LROLT. Before transplantation, he had pancytopenia which was probably hepatitis associated, and viral suppression was suspected after bone marrow (BM) biopsy. After the transplantation, he developed progressive pancytopenia and a diagnosis of aplastic anemia was made via BM biopsy. With immunosuppressant agents (cyclosporine, methylprednisolone), cytokine therapy (granulocyte-colony stimulating factor (G-CSF), macrophage-colony stimulating factor (M-CSF), recombinant human erythropoietin (rhEPO)) was effectual and the patient recovered from pancytopenia. He was discharged from the hospital 57 d after the liver transplantation and remains well 1 yr after LROLT. Combined cytokine therapy with high doses of G-CSF, M-CSF and rhEPO appeared to be effective in the treatment of aplastic anemia following liver transplantation for non-A, non-B, non-C hepatitis. Since M-CSF activates macrophages, it may have contributed to the graft rejection. Careful consideration should be given to the use of high-dose M-CSF in liver transplant patients.

HISTOPATHOLOGICAL FEATURES OF HEPATIC ALLOGRAFT REJECTION IN LIVING-RELATED LIVER TRANSPLANT RECIPIENTS

191 Introduction: Living-related orthotopic liver transplantation(LRLT) has evolved to be a routine procedure over the past seven years in Japan. Since in most instances the donor is a parent, it is expected that the parent-child homology imparts an immunologic advantage against organ rejection. Minimized ischemia-reperfusion injury also may protect hepatic allograft rejection. However, the histopathological features of hepatic allograft rejection under LRLT are less clearly defined. Materials and Methods: A group of 37 consecutive patients who underwent LRLT at our institute between April 1995 and May 1997 was retrospectively studied. All patients primarily were administered FK506 with corticosteroids. Fifty-three liver needle biopsy specimens taken from 22 patients were available for this study. The biopsies were performed when the patients showed clinical or biochemical signs of graft dysfunction. Biopsy specimens were re-evaluated, and if the diagnosis of acute rejection was made, it was graded based on the Banff schema in 1995. Results: In the 37 patients the overall six months' survival rate was 75.7%. All patients had neither primary non function nor retransplantation. Twenty-one (56.8%) of 37 patients developed at least one episode of acute rejection. There were 49 episodes of rejection, and 33 were confirmed by biopsy. Sixteen episodes of acute rejection were diagnosed clinically and/or biochemically, and treated without biopsies. Thirty-four of 53 biopsy specimens had histological evidence of rejection; 14 mild, 14 moderate, 5 severe acute rejection, and one chronic rejection. Most of the portal inflammation was mild to moderate, and the venous endothelial inflammation was also mild except for five specimens that were diagnosed as severe acute rejection. However, there were large number of specimens that showed severe bile duct damage. Perivenular hepatocyte necrosis is observed in three specimens graded as severe. Only one patient who developed steroid-resistant acute rejection and chronic rejection received a course of muromonab-CD3. No graft was lost due to unresolved rejection. Four episodes of acute rejection were spontaneously resolved without additional immunosuppression. Of 31 cases that were followed more than one year after transplantation, although fourteen patients were weaned off steroids, histological severity did not correlate with steroid withdrawal. Conclusion: It is suggested that histological features of hepatic allograft rejection of LRLT are milder than those of cadaveric orthotopic liver transplantation reported by other groups, and the incidence of primary non function and chronic rejection were remarkably low.

HISTOPATHOLOGICAL FEATURES OF HEPATIC ALLOGRAFT REJECTION IN LIVING-RELATED LIVER TRANSPLANT RECIPIENTS

191 Introduction: Living-related orthotopic liver transplantation(LRLT) has evolved to be a routine procedure over the past seven years in Japan. Since in most instances the donor is a parent, it is expected that the parent-child homology imparts an immunologic advantage against organ rejection. Minimized ischemia-reperfusion injury also may protect hepatic allograft rejection. However, the histopathological features of hepatic allograft rejection under LRLT are less clearly defined. Materials and Methods: A group of 37 consecutive patients who underwent LRLT at our institute between April 1995 and May 1997 was retrospectively studied. All patients primarily were administered FK506 with corticosteroids. Fifty-three liver needle biopsy specimens taken from 22 patients were available for this study. The biopsies were performed when the patients showed clinical or biochemical signs of graft dysfunction. Biopsy specimens were re-evaluated, and if the diagnosis of acute rejection was made, it was graded based on the Banff schema in 1995. Results: In the 37 patients the overall six months' survival rate was 75.7%. All patients had neither primary non function nor retransplantation. Twenty-one (56.8%) of 37 patients developed at least one episode of acute rejection. There were 49 episodes of rejection, and 33 were confirmed by biopsy. Sixteen episodes of acute rejection were diagnosed clinically and/or biochemically, and treated without biopsies. Thirty-four of 53 biopsy specimens had histological evidence of rejection; 14 mild, 14 moderate, 5 severe acute rejection, and one chronic rejection. Most of the portal inflammation was mild to moderate, and the venous endothelial inflammation was also mild except for five specimens that were diagnosed as severe acute rejection. However, there were large number of specimens that showed severe bile duct damage. Perivenular hepatocyte necrosis is observed in three specimens graded as severe. Only one patient who developed steroid-resistant acute rejection and chronic rejection received a course of muromonab-CD3. No graft was lost due to unresolved rejection. Four episodes of acute rejection were spontaneously resolved without additional immunosuppression. Of 31 cases that were followed more than one year after transplantation, although fourteen patients were weaned off steroids, histological severity did not correlate with steroid withdrawal. Conclusion: It is suggested that histological features of hepatic allograft rejection of LRLT are milder than those of cadaveric orthotopic liver transplantation reported by other groups, and the incidence of primary non function and chronic rejection were remarkably low.

New thrombolytic modality ? regional administration of tissue plasminogen activator for hepatic artery and portal vein thromboses after liver transplantation: Case report

A 2 1/2-year-old boy with biliary atresia underwent orthotopic living-related liver transplantation. On the 7th postoperative day, he had an episode of hepatic arterial thrombosis following disseminated intravascular coagulation (DIC) due to severe intraabdominal sepsis. Tissue plasminogen activator was administered regionally and the hepatic arterial flow recovered promptly. On postoperative day 33, portal vein thrombosis occurred and direct tissue plasminogen activator injections into the portal vein improved portal blood flow. However, the patient eventually died of poorly controlled DIC. Throughout the course, color Doppler ultrasonogram and arterial ketone body ratio were good indicators of hepatic arterial and portal blood flow. When hepatic arterial thrombosis and portal vein thrombosis occur, retransplantation is often inevitable. Thus, while the patient is awaiting a suitable donor, it could be possible to maintain blood flow to the graft with this new thrombolytic therapy.

Incidence of rejection in pediatric patients following living-related orthotopic liver transplantation (OLT)

Incidence of rejection in pediatric patients following living-related orthotopic liver transplantation (OLT)