A. Lucianetti

Split-liver transplantation eliminates the need for living-donor liver transplantation in children with end-stage cholestatic liver disease.

Background. End-stage cholestatic liver disease (ESCLD) is the main indication for liver replacement in children. Pediatric cadaver–organ-donor shortage has prompted the most important evolutions in the technique of liver transplantation, in particular living-donor liver transplantation (LDLT) and split-liver transplantation (SLT). Methods. Between November 1997 and June 2001, 127 children with ESCLD were evaluated for liver transplantation, and 124 underwent 138 liver transplantations after a median time of 40 days. Causes of liver disease were congenital biliary atresia (n=96), Alagille’s syndrome (n=12), Byler’s disease (n=8), and other cholestatic diseases (n=8). Results. Ninety (73%) patients received a split-liver graft, 28 (23%) a whole liver, and 6 (4%) a reduced-size liver. Overall 2- and 4-year patient survival rates were 93% and 91%, respectively; the 2- and 4-year graft-survival rates were 84% and 80%, respectively. In split-liver recipients, 4-year patient and graft-survival rates were 91% and 83%, respectively; these were 93% and 78%, respectively, in whole-liver recipients and 67% and 63%, respectively, in reduced-size liver recipients. Retransplantation rate was 11%, whereas mortality rate was 8%. Overall incidence of vascular and biliary complication were 16% and 27%, respectively. Conclusions. SLT can provide liver grafts for children with ESCLD with an outcome similar to the one reported following LDLT, eliminating mortality while they are on a transplantation wait list. The need for pediatric LDLT should be reevaluated and programs of SLT strongly encouraged and supported at a national and international level.

Extended right split liver graft for primary transplantation in children and adults

Skepticism remains about the use of the extended right (ER) split graft (segments I, IV–VIII) for adult liver transplantation. We analyzed the results of primary liver transplantation performed with an ER graft in adult and in pediatric recipients. At our Institution, between October 1997 and June 2005, 32 primary liver transplantations with an ER graft were performed in 22 adult and 10 pediatric recipients. All the splitting procedures were performed in situ. Actuarial patient and graft survival among the adult recipients of the ER graft were 100% and 100% at 1 year, and 94% and 94% at 5 years. In the pediatric recipients, patient and graft survival were 90% and 79% both at 1 and 5 years. No hepatic artery thrombosis (HAT) occurred in the adult group, while in the pediatric recipients HAT occurred in two cases. A higher biliary morbidity occurred in the ER graft group when compared with the whole size graft 34% versus 13% (P = 0.03). However, this did not affect patient and graft survival. The results of this study may represent a further argument in favor of extensive splitting of all suitable grafts.

Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma.

Romano F, Stroppa P, Bravi M, Casotti V, Lucianetti A, Guizzetti M, Sonzogni A, Colledan M, D’Antiga L. Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma.
Pediatr Transplantation 2011: 15: 573–579.

On-line monitoring of lung mechanics during spontaneous breathing: a physiological study.

BACKGROUND Monitoring the mechanics of breathing in patients with advanced chronic obstructive lung diseases prior to lung transplantation is useful to characterize changes in the mechanical properties of the lungs. On-line methods of monitoring immediately process the data for clinical decisions. However, the few available methods are so far limited to monitor respiratory mechanics in ventilator-dependent patients. We investigated whether on-line monitoring of the lung mechanics, including intrinsic PEEP, was feasible in spontaneously breathing patients. METHODS In 9 stable patients with chronic obstructive pulmonary disease (COPD) and 11 with cystic fibrosis (CF) undergoing the procedure for the lung transplantation waiting list, we applied 2 methods of on-line monitoring (modified recursive least squares, RLS and modified multiple linear regression methods, SLS) of intrinsic PEEP (P(0)), dynamic lung elastance (E(Ldyn)) and inspiratory resistance (R(Linsp)), and compared them with an off-line graphical analysis (GA), our reference technique. RESULTS In CF patients, there was no difference between methods, while in COPD, the median values of E(Ldyn) and R(Linsp) were significantly different between GA/SLS and GA/RLS, respectively (Dunns, p<0.05). However, the correlation was very high for all comparisons, particularly for E(Ldyn) (R>0.98) and R(Linsp) (R>0.93). Moreover, Bland-Altman plots showed that the mean differences were consistently low and the intervals of agreement reasonable. CONCLUSIONS Our study suggests that on-line methods are reliable for monitoring lung mechanics in spontaneous breathing patients with severe lung diseases and could help clinicians in their decision-making process.

Circulating Epstein-Barr virus DNA to monitor lymphoproliferative disease following pediatric liver transplantation

Abstract Epstein‐Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV‐infected lymphocytes can help in identifying patients at risk of post‐transplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/105 peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/105 PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.

Lung transplantation with grafts from elderly donors: a single-center experience.

INTRODUCTION Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation. METHODS Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56-66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15-54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study. RESULTS Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85). CONCLUSION Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.

Bone mass and body composition in children with chronic cholestasis before and after liver transplantation.

OSTEOPENIA is a common complication in chronic cholestatic liver diseases, and a number of reports have described various degrees of osteopenia, with or without fracture, in adults and children. It is not known if this bone disease is a result of a deficiency in vitamin D, minerals, or hormones, or whether it reflects the malnutrition that accompanies cholestatic diseases. Orthotopic liver transplantation (OLT) is often the only chance of recovery, but is itself known to cause a reduction in bone mineral content in adult patients. The decrease in bone mass occurs during the first 6 months following OLT and then a steady increase is observed after 1 year, and, as might be expected, most pathologic fractures occur within 6 months after OLT and their incidence decreases after 1 year. The causes of the bone loss observed during the first months after OLT are still debated, but the administration of steroids and immunosuppressive drugs may play a role. Little is known about the effect of OLT on bone mass in infants and children. The bone mineral content of children with chronic cholestasis diseases normalizes within a few months of transplantation. To our knowledge, no data are available concerning body composition in infants and children with cholestatic diseases before and after OLT, and thus we used dual-energy X-ray photon absorptiometry (DXA) measurements of total bone mass and body composition to monitor the posttransplantation growth of such patients.

Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

Sequential bilateral single lung‐liver transplantation (SBSL‐LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio‐pulmonary by‐pass (CPB). We performed SBSL‐LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno‐venous by‐pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow‐up of 670 days (range 244–1533). Combined SBSL‐LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

Rejection and tacrolimus conversion therapy in paediatric liver transplantation

Abstract Rejection and efficacy of rescue therapy with tacrolimus were evaluated in 50 children who underwent primary, ABO‐compatible, liver transplantation. Six patients who died within the first week and one child who underwent retransplantation from an ABO‐incompatible donor were excluded from the study. No patient or graft were lost due to rejection. We observed 48 episodes of rejection in 33 patients. Fourteen patients required conversion to tacrolimus for steroid‐resistant rejection with resolution of rejection. One of these children developed PTLD. Other indications for conversion were neurotoxicity and hirsutism. One patient developed blindness of unknown origin after the conversion. Other side effects of tacrolimus were minor and resolved by lowering the dose. Five patients developed rejection after conversion; all achieved resolution with either steroid therapy or increase of tacrolimus dose. In conclusion, our study confirms that tacrolimus is an effective rescue therapy for paediatric liver transplantation.

Rescue FK506 early conversion for refractory rejection after pediatric liver transplantation: experience in 20 children

Abstract Tacrolimus (FK506) is an effective and relatively safe novel immunosuppressant able to revert refractory rejection after pediatric liver transplantation (LTx). Between April 1993 and October 1996, 20 pediatric patients were converted to tacrolimus for biopsy‐proven, steroiD‐resistant liver rejection. The mean follow‐up was 18 months. The median time from LTx to switch was 20 days. Tacrolimus was administered per os at a mean dosage of 0.23 mg/kg per day to maintain median blood levels of 10.8 ng/ml at 1 week and 9.2 ng/ml at 1 year from the switch. Of the 20 patients, 15 are alive and they all recovered from rejection without the need of OKT3 after conversion. The major causes of death were: one multiorgan failure, two infections (cytomegalovirus Aspergillus), one bowel perforation, and one posttransplant lymphoproliferative disease. One patient experienced late side effects and was reconverted to cyclosporine when she was already rescued from hepatic allograft rejection. The results confirm that an earlier conversion to tacrolimus should be recommended after pediatric liver transplantation in order to revert hepatic allograft rejection with the best safety profile.