Intestinal transplantation

Intestinal transplantation is often the only alternative form of treatment for patients dependent on total parenteral nutrition for survival. Although a limited number of intestinal transplantations have been performed, results with FK 506 immunosuppression are comparable to those for other organ transplants. The impact of successful intestinal transplantation on gastroenterology will likely be similar to the impact of kidney and liver transplantation on nephrology and hepatology

Intestinal transplantation in children under FK 506 immunosuppression

Intestinal transplantation, solitary (n = 3) or in combination with the liver (n = 7), was performed in 10 pediatric patients with intestinal failure. The liver was only replaced if there was liver failure and portal hypertension. Immunosuppression was based on FK 506. Two patients died, one of graft-versus-host disease and one of lymphoproliferative disease. One patient was still in the intensive care unit 1 month posttransplantation due to perioperative complications. The function of the intestinal grafts in the remaining patients is normal. All nutrition and medications including immunosuppression are being administered enterally. This series indicates that small bowel transplantation, alone or in combination with the liver, is feasible in pediatric patients. © 1993

Early tolerance in pediatric liver allograft recipients

The authors report on six pediatric liver transplant recipients for whom allograft tolerance occurred shortly after transplantation (ie, less than 1.5 years). All the patients had associated life-threatening viral complications. They are currently immmunocompetent. The tolerant state may be related to the development of a TH2 cytokine pattern. © 1994

Indications for pediatric liver transplantation

Two hundred fifty pediatric (<18 years of age) patients underwent orthotopic liver transplantation because of end-stage liver disease and were given combination therapy with cyclosporine and prednisone. The most common indications for transplantation in decreasing order of frequency were biliary atresia, inborn errors of metabolism, and postnecrotic cirrhosis. The 5-year actuarial survival for the entire group was 69.2%. Age and diagnosis did not influence survival. Infections were the most common cause of death, followed by liver failure and cerebrovascular accident. The impact of retransplantation on survival depends on the indication. The survival is better when retransplantation is carried out after rejection than because of technical complications, and the latter has a better survival than does primary graft nonfunction. The difference in survival among these groups is statistically significant. The quality of life for 164 of 173 survivors is good to excellent; only nine children are currently experiencing medical problems. A persistent problem in pediatric transplantation is the scarcity of small donors. © 1987 The C. V. Mosby Company

Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death

Basiliximab in pediatric liver transplantation: A pharmacokinetic-derived dosing algorithm

The pharmacokinetics and immunodynamics of basiliximab were assessed in 37 pediatric de novo liver allograft recipients to rationally design a dose regimen for this age-group. In part one of the study, patients were given 12 mg/m 2 basiliximab by bolus intravenous injection after organ perfusion and on day 4 after transplant. An interim pharmacokinetic evaluation supported a fixed-dose approach for part two of the study in which infants and children received two 10-mg doses of basiliximab and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for screening for anti-idiotype antibodies and analysis of basiliximab and soluble interleukin-2 receptor (IL-2R) concentrations. Basiliximab clearance in infants and children  5 L of ascites fluid drainage tended to have lower systemic exposure to basiliximab. CD25-saturating basiliximab concentrations were maintained for 27 ± 9 days in part one of the study (mg/m 2 dosing) with infants exhibiting the lowest durations. CD25 saturation lasted 37 ± 11 days in part two of the study, based on the fixed-dose regimen (p = 0.004 vs. mg/mg 2 dosing), but did not show the age-related bias observed in part one of the study. Anti-idiotype antibodies were detected in four patients, but this did not influence the clearance of basiliximab or duration of CD25 saturation. All 40 enrolled patients were included in the intent-to-treat clinical analysis. Episodes of acute rejection occurred in 22 patients (55%) during the first 12 months post-transplant. Three patients experienced loss of their graft as a result of technical complications, and six patients died during the 12-month study. Basiliximab was well tolerated by intravenous bolus injection, with no cytokine-release syndrome or other infusion-related adverse events. Hence, basiliximab was safe and well tolerated in pediatric patients undergoing orthotopic liver transplantation. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients < 35 kg in weight should receive two 10-mg doses and those ≥ 35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose should be given within 6 h after organ perfusion and the second on day 4 after transplantation. A supplemental dose may be considered for patients with a large volume of drained ascites fluid relative to body size.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72080/1/j.1399-3046.2002.01086.x.pd