M. Guizzetti

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.

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.

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.

Specific autologous cytotoxic T lymphocytes for chronic varicella in a liver transplanted child.

Abstract:  Infections by herpesviruses may have severe complications in liver transplant patients. Although prophylactic varicella zoster virus vaccination is strongly recommended and widely applied, severe infection may still occur. We report the case of systemic chronic varicella, which developed in a liver allograft recipient, unresponsive to antiviral drug treatment, successfully treated by varicella zooster‐specific CTL. Graft failure ensued, likely, because of massive cytolysis of infected hepatocytes. The patient, who was re‐transplanted in the absence of signs of varicella zooster reactivation, is now well and disease free 3 yr after second liver transplant.

A Randomized Trial For Tacrolimus And Steroids Vs. Tacrolimus And Basiliximab In Pediatric Liver Transplantation

Aims: Basiliximab is a monoclonal antibody against IL-2 receptor. A comparison between immunosuppression carried out with Tacrolimus (TAC) and Steroids (ST) VS. Tacrolimus and Basiliximab (BAS) was performed to evaluate the efficiency and safety of these two drugs association after pediatric liver transplantation. Methods: A randomized prospective trial was started in June 2001 at the Liver Transplantation Center in Bergamo, Italy. Patients receiving primary liver transplantation were enrolled in two groups: group A (TAC ST) or in group B (TAC BAS). A total of 64 patients were recruited in the study, 32 in group A and 32 in group B. Mean age was 3 yrs (0.5-16.9) and mean weight was 13.3 (4-65). The main indication for transplantation was biliary atresia. Primary endpoint of the study was the incidence of acute rejection (ACR) in the first three months. Secondary endpoints of the study were the cumulative incidence and severity of ACR, patient and graft survival, and incidence of adverse events. Tacrolimus was given at an initial dose of 0.08 mg/kg/die and then adjusted to obtain trough levels between 10 and 15 ng/ml during the first three months and of 5/10 ng/ml after the 3 month. ST were administered at the dose of 2 mg/kg and tapered before being stopped after three months. BAS was given at the dose of 20 mg iv on postoperative day 0 and 4. Results: Overall survival rate was 92%, 93% for patients in group A and 90% for patients in group B. 4 patients were excluded from the study (1 in group A and 3 in group B) for early death or discontinuation of immunosuppression. Rejection episodes were 7 in group A (22%) and 2 in group B (7%). Mean RAI score was 6 for group A, while the two patients in group B had a RAI of 4. Rejection occurred after 11 days (mean) in group A and after 20 and 223 days in the two cases in group B. One patient in group B had PTLD. Rates of EBV seroconversion were respectively (group A vs. group B) 25% and 17%. CMV infection rates were 19% vs. 13%. Sepsis occurred in 25% of patients in group A vs. 13% in group B. Conclusions: ACR seems to be less frequent in the BAS group and, even when it occurs, shows a delayed onset and a less severity. Severe infectious episodes are more rare without the use of steroids. Adverse effects of BAS were not observed in this study. Long term follow-up needs to clarify the effect of these results on the occurrence rate of late complications and chronic rejection.

The successful management of a Bronchoesophageal fistula after lung transplantation: a case report

We describe an unprecedented, disastrous complication after bilateral lung transplantation (BLT), a bilateral bronchial dehiscence with a right bronchoesophageal fistula leading to life‐threatening septic shock. We also report the successful endoscopic management of this complication by double stenting and stress the efficacy of the multidisciplinary approach to this critical case.

Intestinal Transplantation in Children: The First Successful Italian Series

The preliminary experience of the first Italian program of pediatric intestinal transplantation is presented herein. A multidisciplinary group with broad experience in pediatric solid organ transplantation started the program. Nine children with complications of chronic intestinal failure were listed for transplantation. One child died on the waiting list; one received an isolated liver transplantation; three isolated intestinal; three multivisceral; and one, a combined liver/intestine transplantation. There was no in-hospital mortality, and all children were weaned from parenteral nutrition. The recipient of the multivisceral graft died after 14 months for unknown causes. All other recipients are alive after a median follow-up of 13 months. Patient and graft actuarial survivals for recipients of intestinal grafts were 100% at 1 year and 75% at 2 years.

Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation:

Context: Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC. Objectives: In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC). Design: Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival. Results: Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival. Conclusion: Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.