Selenium homocholic acid taurocholate scanning, selenium-75-labeled bile acid, a novel method for testing the function of the terminal ileum in small bowel transplant recipients: a pilot study.

INTRODUCTION: The terminal ileum (TI) is important for the active reabsorption of bile salts and is the site of allograft rejection; disruption of enterohepatic circulation (EHC) may give insights to inflammatory and other physiologic processes at the TI. SUBJECTS AND METHODS: Four children aged 5 to 12 years who had received small bowel transplantation (SBTx), 3 recovering from post-transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were studied. Two of the 4 had stoma reversal. Another child (15 years) with progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver transplantation and biliary diversion, was studied. Selenium homocholic acid taurocholate scanning ((75)SeHCAT) capsule was given orally (n = 3) or via introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was done 4 hours later and on days 1 to 5. RESULTS: The normal 3-day bile salt retention is 30% to 70% of baseline and normal adult biological half-life, t½ is 62 ± 17 hours. The results in children with a stoma were very low (0.1% at 7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and t½ closer to the reference range (18% at 29 hours; 22% at 33 hours). The child with PFIC + biliary diversion had an initial very high gamma emission from the stoma bag suggesting excellent reabsorption of bile salts from his TI, but retention was 0.6% and t½ 9.8 hours, demonstrating efficient biliary diversion. CONCLUSION: These results confirm children with stomas malabsorb bile acids, which can be ameliorated after stoma closure. SeHCAT demonstrated that the biliary diversion was working well and may be helpful in preoperative assessment of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation.

Isolated liver transplant in infants with short bowel syndrome: insights into outcomes and prognostic factors.

OBJECTIVE: Selected infants with short bowel syndrome (SBS) and progressive intestinal failure associated liver disease (IFALD) may benefit from isolated liver transplantation (iLTx). The aim of the study is to identify risk factors for unfavourable outcome in iLTx. PATIENTS AND METHODS: A retrospective review of medical records from 1998 to 2005 was undertaken. Risk factors were assessed by comparing long-term survivors with those who died after iLTx. RESULTS: Fifteen iLTx were performed in 14 infants with IFALD. All were parenteral nutrition (PN) dependent, but had tolerated enterally 54% (38-100) of energy intake before iLTx. Median residual bowel was 60 cm (30-200). Eight out of 14 had intact ileocaecal valve (ICV). Median bilirubin was 298 micromol/L (87-715) and all had portal hypertension. Eight out of 9 survivors were weaned from PN after median 15 months. In 4 out of 9 children, nontransplant surgery after iLTx facilitated intestinal adaptation. Growth velocity had improved at 3 years after iLTx (P=0.001). Five children who died had poor enteral tolerance following iLTx (P<0.002), which correlated with pretransplant dysmotility seen in 4 out of 5 children shown by contrast studies (P=0.02)and increased frequency of line infections before (>6/year P<0.04) and after (P<0.001) iLTx. CONCLUSIONS: Isolated liver transplantation is a lifesaving option for selected children with SBS and IFALD. Revised criteria are proposed: progressive IFALD; 50 cm functional bowel in absence of ICV or 30 cm with ICV; 50% daily energy intake tolerated enterally for 4 weeks with satisfactory growth; and children with dysmotile bowel should be assessed for combined liver/bowel transplant unless the dysmotility is resolved and associated with minimal line infections.

Renal function following liver transplantation for unresectable hepatoblastoma.

Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.

New perspective for the management of near-total or total intestinal aganglionosis in infants.

BACKGROUND/PURPOSE: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis. METHODS: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II). RESULTS: Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6). CONCLUSIONS: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease.

Concomitant basiliximab with low-dose calcineurin inhibitors in children post-liver transplantation.

Orthotopic liver transplantation (OLT) is effective therapy for end-stage liver disease but immunosuppression with calcineurin inhibitors (CNI) leads to significant nephrotoxicity, resulting in either a reduction of dosage to below the therapeutic level or omission of the drug altogether. Basiliximab (Bx) is a human/mouse chimeric monoclonal antibody that inhibits binding of interleukin-2 (IL-2) to IL-2 receptors and thus prevents proliferation of T cells, which is the main step in the development of acute cellular rejection. The aim of this study was to identify the role of Bx in the prevention of acute cellular rejection and in the reduction of nephrotoxicity in children post-liver transplantation. We evaluated three children (19 months, 22 months, and 11 yr of age; one male, two female) who were treated with Bx post-OLT on compassionate grounds. The indications were: nephrotoxicity in two children, requiring re-transplantation for hepatic artery thrombosis and recurrent giant cell hepatitis, respectively; and nephrotoxicity secondary to chemotherapy for hepatoblastoma in the third child. All patients received 10 mg of Bx, at OLT and on Day 4. Tacrolimus (0.15 mg/kg/day) was started at 48 h (n = 2) and cyclosporin (5 mg/kg/day) at 2 weeks (n = 1). Trough levels of tacrolimus were maintained at 5-8 ng/mL and trough levels of cyclosporin at 100-150 mg/L for the first 3 months. All patients received methylprednisolone (2 mg/kg) with azathioprine (1.5 mg/kg) (n = 2) and/or mycophenolate mofetil (20 mg/kg) (n = 1). The glomerular filtration rate (cGFR) was calculated using the Schwartz formula before and 10 weeks after transplant. Bx was found to be easy to administer and no major side-effects were reported. One child had two episodes of mild acute rejection at 5 and 9 weeks post-OLT and one developed chronic rejection requiring re-transplantation at 9 weeks post-OLT. One child did not develop rejection. The mean pretransplant cGFR was 58.1 (54.6-64.1) mL/min/m2. Within 10 weeks of transplantation, the cGFR had improved by 69% to a mean of 116 (88-157.6) mL/min/m2. To conclude, Bx was well tolerated in all children and had a renal sparing effect. It was effective in preventing early acute rejection, but the combination of Bx and low-dose CNI drugs did not prevent late acute or chronic rejection. Further studies to evaluate the appropriate levels of CNI immunosuppression with Bx are required.

Techniques for and outcome of liver transplantation in neonates and infants weighing up to 5 kilograms.

BACKGROUND: Neonates and small infants represent less than 5% of paediatric candidates for liver replacement. Most cases present under urgent conditions and receive grafts from large donors. Surgical techniques must be adapted for adequate graft preparation, vascular reconstruction, and abdominal closure. METHODS: Technical aspects and outcome of 15 liver transplantations in infants weighing less than 5 kg performed at our unit were analysed retrospectively. RESULTS: Liver transplantation was performed under urgent or highly urgent condition in 13 cases. Reduced or split liver grafts were used in all cases (median donor to recipient weight ratio, 9), including a monosegmental graft in 2 cases. In 10 cases, vascular reconstruction was done using a vascular conduit (5, 4, and 1 for artery, portal, and hepatic veins, respectively) and a delayed closure of the abdomen was necessary in 7 children. Postoperative complications were as follows: thrombosis of hepatic artery (n = 1) or portal vein (n = 1), gastrointestinal haemorrhage (n = 2), intraperitoneal bleeding (n = 1), biliary stricture (n = 2), septicaemia (n = 1). Two infants died of brain damage with a functioning graft. One child underwent retransplant for chronic rejection. CONCLUSIONS: Overall, survival rate is 60% (median follow-up, 34 months), which compares favourably with older patient groups when case mix is comparable.

Outcome of liver retransplantation in children.

Irreversible liver graft failure is a life-threatening complication. We reviewed the first 200 pediatric liver transplantations in Birmingham. Forty-one children developed primary graft failure, 9 of whom developed secondary graft failure. The main indications for graft failure were primary nonfunction (PRNF; 8 patients), vascular complications (VASC; 23 patients), and chronic rejection (CHRE; 19 patients). Thirty-two children underwent retransplantation (ReTx) (21 children received reduced grafts; 11 children, whole hepatic grafts). Patient survival was significantly worse for retransplant recipients compared with children receiving a single graft (63% v 76. 5% actuarial patient survival at 1 year; P <.05). Primary graft 1-year actuarial survival was 74% in first grafts compared with 47% for regrafts (P <.05), but improved with time. The graft 1-year survival rate was 55% for whole grafts and 45% for reduced and/or split grafts in the first 100 grafts compared with 83% and 66% in the second 100 grafts, respectively (P <.01). Emergency ReTx within a month of transplantation was associated with more complications and a worse outcome (1-year survival rate, 37%) compared with patients who underwent ReTx later (1-year survival rate, 72%; P <. 01). The incidence of primary graft failure decreased from 33% in the first 100 grafts to 16% in the second 100 grafts (P <.01), as did the incidence of PRNF, which decreased from 8% to 0% (P <.05). Although the rates of graft failure from VASC decreased from 15% to 8% (P =.2) and CHRE decreased from 11% to 8% (P =.6), neither reached statistical significance. The improved results overall are because of advances in surgical techniques, intensive care management, and graft preservation and refinements in immunosuppression. We conclude that ReTx for a child with primary graft failure is justified.

Clinical features and prognosis of children assessed for isolated small bowel or combined small bowel and liver transplantation.

The hepatic histology and clinical status of 37 children on long-term parenteral nutrition (PN) referred for consideration of small bowel transplantation were determined. Seventy five percent of the children had splenomegaly and plasma bilirubin level of greater than 100 mumol/L. All of 21 children who underwent liver biopsy, had increased fibrosis, but only half had established cirrhosis. Thirty-one children were considered to be in need of transplantation (combined liver and bowel transplant, 29; isolated bowel transplant, 2), but only 13 were stable enough to be placed on the transplant list. Seven out of the thirteen children waiting have died because of lack of size-matched organs, and the overall mortality rate of the 37 children was 70%. The main risk factors for death within 6 months were bilirubin level of greater than 100 mumol/L, splenomegaly, and cirrhosis (P = .01). The natural history of PN-associated liver disease is that of progressive liver failure and death 6 to 12 months after onset of cholestasis, defined as bilirubin level of greater than 100 mumol/L. The development of cirrhosis occurs after the onset of jaundice, so early referral may also permit some children to be offered isolated bowel transplantation, which has better outcome than combined liver and bowel transplantation.

Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors.

The medical records of 74 neonates dependent on parenteral nutrition for at least 21 days after emergency abdominal surgery (performed between 1988 and 1992) were reviewed respectively. The role of enteral starvation, prematurity, composition and duration of parenteral nutrition, and sepsis in the evolution of parenteral nutrition-related cholestasis was evaluated by multiple regression analysis. The most important factors for cholestasis were low gestational age (median, 34 weeks), early exposure to parenteral nutrition, and sepsis. Episodes of sepsis were associated with a 30% increase in the bilirubin level. Enteral starvation and composition and the duration of parenteral nutrition solutions did not correlate significantly with the development of cholestasis. Prevention of sepsis should be the priority in minimising cholestasis in postsurgical neonates who are dependent on parenteral nutrition.