Sean Cao

Long-term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus

Cao S, Cox KL, Berquist W, Hayashi M, Concepcion W, Hammes GB, Ojogho OK, So SKS, Frerker M, Castillo RO, Monge H, Esquivel CO. Long‐term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus. Pediatr Transplantation 1999: 3: 22–26.

Epstein-Barr virus lymphoproliferative disorders after liver transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent a spectrum of histological and immunological abnormalities, ranging from benign polyclonal B-cell hyperplasia to monoclonal malignant lymphoma. The important role of Epstein-Barr virus (EBV) in PTLD in liver transplant patients, particularly in pediatric recipients, is reviewed. Understanding the risks of EBV infection, the clinical presentations and diagnosis of PTLD, and its pathophysiology are crucial to the management of these disorders. Current treatment methods have resulted in better outcomes of these disorders, which in the past were uniformly fatal.

Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation

BACKGROUND Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

Human hepatocytes produce an isoform of FAS that inhibits apoptosis.

BACKGROUND Fas (Apo-1/CD95), a member of the tumor necrosis factor receptor family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody. Fas is expressed by cells of the immune system and by some nonlymphoid tissues. Numerous studies have suggested that the Fas pathway may play a role in the rejection of allografts. Functional, soluble forms of the Fas receptor are produced by activated peripheral blood mononuclear cells and some transformed cell lines. The purpose of this study was to determine if soluble variants of Fas are produced in the liver and to determine if blockade of the Fas pathway, by liver-derived soluble Fas, inhibits Fas-mediated apoptosis. METHODS Liver and purified hepatocyte specimens were analyzed for Fas transcripts by reverse transcriptase-polymerase chain reaction with primers that span the transmembrane region of the molecule. Bile and cell lysates were analyzed for soluble Fas by specific enzyme-linked immunosorbent assay. Lysates were prepared from normal liver and hepatocytes and utilized to block Fas-mediated apoptosis of Jurkat cells as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometry. RESULTS A variant form of Fas is abundantly expressed in normal liver and purified hepatocytes. This variant form of Fas is expressed in all normal liver specimens but only in half of the liver specimens obtained during allograft rejection. The levels of soluble Fas diminish in patients undergoing liver allograft rejection in contrast to patients with stable grafts. Importantly, a soluble form of Fas is produced in the liver by hepatocytes and can specifically inhibit Fas-mediated apoptosis. CONCLUSION These data raise the possibility that soluble Fas, produced by hepatocytes, may influence the immune response by blocking Fas-mediated apoptosis and, thus, may have a role in liver transplantation.

Potential Effect of Cyclosporin A in Formation of Cholesterol Gallstones in Pediatric Liver Transplant Recipients

Recent advancements in liver transplantationhave resulted in extended survival both for grafts andrecipients. Such improvement, together with the shortageof donor organs has prompted expansion of the donor pool to include less than ideal donors,especially in life-threatening situations. The use ofolder liver donors has been associated with lowerlong-term survival. However, potential morbidity such as gallstone formation has not been explored.We analyzed bile composition in a child who developedcholesterol gallstones in the proximal bile duct twoyears after undergoing emergency liver transplantation with a liver from a 78-year-old donor. Oraladministration of ursodeoxycholic acid (ursodiol)shifted the cholesterol composition of the bile from asupersaturated, potentially crystallized state to aliquid (micellar) state. Unlike cyclosporin A, FK506showed an increase in the proportion of chenodeoxycholicacid and a decrease in the proportion of cholic acid,and thus may exhibit minimal or no hepatotoxic effect. Thus, in donor livers with factorsknown to be associated with cholesterol gallstoneformation (such as age, sex, or obesity), one mayconsider analyzing the bile composition at the time ofprocurement. Depending on cholesterol and bile acidcomposition, the use of FK506 with or without additionof ursodeoxycholic acid may be warranted.

Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: A case report

Since the first successful report regarding the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) as an alternative to surgical decompression of portal hypertension, this method has been used extensively as a temporizing measure in controlling refractory variceal bleeding before liver transplantation in adults with cirrhosis. There are few reports of TIPS in pediatric patients because variceal bleeding in most of these patients can often be managed conservatively without invasive intervention. Recently, successful use of TIPS to treat complications of portal hypertension has been described in two children ages 10 and 13. To our knowledge, there are no reports of TIPS used in infants under the age of 1 year. The authors report a case in which TIPS was used to successfully control variceal bleeding in a 10-month-old infant before consideration for hepatic transplantation.