M Burdelski

Long‐term results of pre‐emptive liver transplantation in primary hyperoxaluria type 1

Abstract: In primary hyperoxaluria type 1 (PH 1), deficiency or mis‐targeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over‐production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end‐stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre‐emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow‐up 3–5.7u2003yr after performing successful PLTx in four children (at the age of 3–9u2003yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27–98u2003mL/min/1.73u2003m2). There was no mortality or long‐term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4u2003weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27u2003mL/min/1.73u2003m2) who showed a stable course for more than 5.7u2003yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.

Effectiveness of Rex shunt in children with portal hypertension following liver transplantation or with primary portal hypertension

Abstract:u2002 Portal vein thrombosis can occur as a result of primary anomalies, after liver transplantation, and for other reasons. It may result in severe complications secondary to portal hypertension, such as bleeding from esophageal or gastric varices, hypersplenism, or impaired somatic growth. In this retrospective study, we analyzed the outcome of 25 children who underwent a Rex shunt procedure. The following venous grafts were used as the shunt: the autologous internal or external jugular vein (nu2003=u200317) or a cryopreserved graft (nu2003=u20035); in three patients the umbilical vein was recanalized. The median follow up time was 109u2003months (range 18u2003days–146u2003months). The best results were achieved in patients in whom an autologous jugular vein segment was used as a vascular graft for the Rex shunt (shunt patency of 88%). In patients with a functioning shunt no further lower or upper gastrointestinal bleeding occurred. And in the entire study population hypersplenism syndrome improved after surgery. In our large cohort of pediatric patients, the Rex shunt has shown to be an effective method to eliminate portal hypertension and to revascularize the liver and thereby prevents the possible consequences of long‐term portosystemic shunting.

Hepatoblastoma in a child with progressive familial intrahepatic cholestasis

Abstract:u2002 End‐stage liver cirrhosis because of metabolic or infectious diseases predisposes to hepatic malignancies like hepatocellular carcinoma. We report the first case of hepatoblastoma incidentally detected in the explanted liver of a 2‐yr‐old child undergoing liver transplantation for cirrhosis because of progressive familial intrahepatic cholestasis (PFIC). The diagnosis was difficult to obtain. The hepatoblastoma was not seen on ultrasound examination of the cirrhotic liver. As we could confirm retrospectively, alpha fetoprotein (AFP) was found elevated prior to transplantation. Two years after successful transplantation, there are no signs of malignancy detectable by clinical and radiological methods. We conclude from this case that PFIC may induce hepatoblastoma and that children with liver cirrhosis should undergo routine screening of serum AFP concentration.

Hypogammaglobulinemia in pediatric liver transplant recipients.

Abstract:u2002 Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post‐transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine‐based standard immunosuppression. Patient 1 was transplanted at the age of 10u2003months for biliary atresia. Eight weeks post‐Ltx the serum IgG was 1.7u2003g/L. Patient 2 was transplanted at the age of 12u2003yr for acute liver failure. Four weeks post‐Ltx the IgG dropped to 2.6u2003g/L. Patient 3 was transplanted at the age of 4u2003months for biliary atresia. Ten weeks post‐Ltx severe hypogammaglobulinemia (IgGu2003<u20031.48u2003g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post‐operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10u2003months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

Basiliximab monotherapy following B-cell lymphoma after pediatric liver transplantation and anti-CD20 therapy

Abstract: The chimeric, monoclonal antibody basiliximab inhibits the proliferation and clonal expansion of activated T cells. To date basiliximab has been used only in combination with other immunosuppressive agents for rejection prophylaxis after solid organ transplantation. An infant underwent liver transplantion (LTx) at the age of 5 months because of biliary atresia. The primary immunosuppression consisted of cyclosporine and prednisolone. As a result of a steroid resistant rejection episode on day 26 post‐LTx we had to switch the initial immunosuppressive regiment to tacrolimus and steroids. Because of severe cholestasis and assumed impaired enteral resorption we were forced to administer an unusually high dosage (2 mg/kg/day) of tacrolimus. Four months after LTx an intestinal B‐cell lymphoma was diagnosed when the patient suffered from a small bowel perforation. After stopping the immunosuppressive medication we started treatment with the anti‐CD20 monoclonal antibody rituximab for B‐cell depletion. During the 12 wk no B cells were detectable in the peripheral blood by flow cytometry. In this setting we started a monotherapy with repetitive doses of basiliximab for immunosuppression. During the following course there was no further rejection and no recurrence of the tumor. From this experience we conclude that monotherapy with basiliximab after LTx and anti‐CD20 treatment for B‐cell lymphoma is efficient and safe.