Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome

Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.     

Renal function outcome in pediatric liver transplant recipients

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.     

Liver transplantation in children with Alagille syndrome: indications and outcome

An AGS is a dominant inherited multisystem disorder caused by mutations in the Notch signaling pathway (JAG1). In our center, 5.3% of liver transplantations (OLT) are performed in children with AGS. Some of the affected children fulfilled criteria for OLT, despite the absence of liver cirrhosis. The aim of our present study was to evaluate the indications and outcome for OLT in children with this complex disorder as clear criteria are difficult to establish in clinical practice. A total of 37 patients were included in a retrospective analysis. Twenty-four children underwent OLT for chronic end-stage liver failure (n = 8) or symptomatic liver disease (n = 16). Patient survival post-OLT was 91.7% after 1 yr, that of graft survival was 87.5%, respectively. Significant post-transplant vascular complications included a mid-aortic syndrome (n = 1) and severe lethal bleeding due to suspected vascular malformation (n = 1). Severe hypercholesterolemia (>800 mg/dL) and xanthomata resolved completely in affected patients. We conclude from our data that indications for OLT in AGS should be extended to patients with severe symptomatic liver disease, even in the absence of liver cirrhosis because of the significantly improved outcome after pediatric OLT in the last decade. Future studies must identify underlying mechanisms of hypercholesterolemia and vascular malformation.     

Morbidity and mortality of children with chronic liver diseases who were listed for liver transplantation in Iran

Liver transplantation is the treatment of choice for end-stage liver disease in children, but donor shortage is still a main problem in this age group. The aim of the present study is to evaluate the complications and mortality of liver disease in children waiting for transplantation. We analyzed medical records of 83 children aged <18 yr, who were listed for liver transplantation but the organ was not available for them between 1999 and 2006. The outcome was assessed from their records or follow-up data. Among the children (mean age, 8 +/- 5 yr; 50.5% boys) listed for liver transplantation, but the organ was not available for them, the common causes of cirrhosis were biliary atresia (27.7%) and cryptogenic (24.1%). The mean follow-up duration was 14 +/- 13.4 months (range 0.5-54 months). Sixty-seven (80.7%) patients developed one or more complications while awaiting transplantation. The most common complications were gastrointestinal bleeding (44.6%), spontaneous bacterial peritonitis (36.1%), infectious complications (28.9%), encephalopathy (24.1%), renal (18.1%), and pulmonary problems (10.8%). Fifty-one (61.4%) patients needed hospital admission because of complications and 26 (31.3%) patients died while awaiting transplantation. About two-thirds of children listed for liver transplantation needed hospital admission because of complications and one-third of them died without any liver transplantation. It seems that more split liver transplantation as well as the introduction of a live-related program in our center will provide many benefits to our children.     

Outcomes of transplantation in children with primary hepatic malignancy

HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (<18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n=377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.     

Improved outcomes in pediatric liver transplantation for acute liver failure

Miloh T, Kerkar N, Parkar S, Emre S, Annunziato R, Mendez C, Arnon R, Suchy F, Rodriguez‐Laiz G, Del Rio Martin J, Sturdevant M, Iyer K. Improved outcomes in pediatric liver transplantation for acute liver failure.
Pediatr Transplantation 2010: 14:863–869. © 2010 John Wiley & Sons A/S. Abstract: OLT is a life‐saving option for ALF. Aim: To evaluate our outcomes in pediatric OLT for ALF. Methods: Retrospective review of our data between 1992 and 2007. Results: Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty‐three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one‐ and five‐yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. Conclusion: We report the largest single‐center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high‐risk cohort and contribute to our excellent outcomes.     

Outcome of pediatric liver transplant recipients in Turkey: single center experience

To summarize the evolution of the pediatric liver transplant program in a developing country. Between April 1997, and September 2003, 32 cadaveric (CD) and 35 living donor (LD) liver transplantations were performed on 61 children (median age 3.8 yr, range 0.5-16) at Ege University Organ Transplantation and Research Center. The patient's charts were reviewed retrospectively. The outcome of patient and graft survival was analyzed and the incidence of graft loss, complications and rejections was calculated. Indications for liver transplantation were metabolic liver disease (n = 17), biliary atresia (n = 14), viral hepatitis (n = 4), autoimmune hepatitis (n = 6), cryptogenic cirrhosis (n = 11), fulminant liver failure (n = 5) and others (n = 5). Seven of 61 children with chronic liver disease had hepatocellular carcinoma concomitantly. Median pediatric end-stage liver disease score was 23 (range 1-54). Seven children (11.4%) were UNOS status I, 44 (72%) were UNOS status II and 10 (16.6%) were UNOS status III. The median follow-up of the study population was 3.6 yr (range 0.5-6). Actuarial patient survival rates at 1, 2, 3 and 4 yr were 86, 86, 71.3 and 65% in the CD group vs. 80, 76, 67 and 67% in the LR group, respectively (p = NS). Patients listed as UNOS status 1 had lower survival rates than patients listed as UNOS status 2 and 3 (p < 0.05). The mortality rate was 26.2%. Graft survival rates were 81, 81, 75 and 64% at 1, 2, 3 and 4-yr respectively. Six patients (9%) underwent retransplantation. The main complications were infections (64.7%) and surgical complications (43.2%) (including biliary complication, vascular problems, postoperative bleeding, small for size and large for size). The incidence of acute cellular rejection was 39.3%, whereas chronic rejection was 7.4%. The result of liver transplantation in Turkish children was slightly inferior to those reported for North American and European children. However, an important characteristic of these patients that distinguishes them from Europe and North America is that most were UNOS status IIa and UNOS status I (44%). Despite technical and medical progress, infectious and biliary problems have continued to be an important cause of mortality in these patients.     

Food allergy after liver transplantation in children: a prospective study

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.     

Distinctive characteristics of diabetes mellitus after hematopoietic cell transplantation during childhood

We report on six patients who developed diabetes mellitus after hematopoietic cell transplantation (HCT). The prevalence in our cohort of long-term survivors after HCT performed below 18 yr of age was 3%. The median age at onset of diabetes was 22.4 yr (range 11.3-34.4). The median period between HCT and diabetes was 10.1 yr (range 5.6-22.1). Five out of the six patients received total irradiation therapy and five had other endocrinological abnormalities. The onset of diabetes in all patients was insidious and none had diabetic ketoacidosis. Body mass indexes at diabetes onset were within normal levels. The clinical and laboratory features that characterized our patients with diabetes after HCT make it difficult to classify them as having type-1 or type-2 diabetes. The relatively high prevalence of diabetes and its insidious onset in this group of patients, advocate clinicians to evaluate carefully even slight variations in fasting blood glucose, usually included in the routine biochemistry follow-up. These data also suggest that HbA1c and oral glucose-tolerance test should be added to the follow-up program of late complications if fasting blood glucose levels are slightly increased.     

Progressive familial intrahepatic cholestasis (Byler disease): current genetics and therapy

Progressive familial intrahepatic cholestasis (PFIC) is a congenital liver disease. First symptoms can frequently be seen shortly after birth. Quality and expectation of life are substantially reduced due to severe pruritus and the complications of progressive liver cirrhosis. PFIC is diagnosed on the basis of characteristic clinical and laboratory parameters and genetic analysis after exclusion of other liver diseases leading to intrahepatic cholestasis. Medical therapy is only effective in a proportion of children with PFIC. Partial biliary diversion (PBD) is nowadays considered the therapy of choice in patients with therapy-refractive pruritus. If performed in time, damage to the liver can be delayed or arrested, thus orthotopic liver transplantation (OLT) can be postponed or even avoided in at least some patients with PFIC. Besides providing a current overview of PFIC, we report on three patients who were successfully treated surgically. One patient was subjected to a new technique of PBD (cholecysto-appendicostomy), the other two had OLT.     

The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation

Calcineurin inhibitor drugs (CNI), cyclosporin and tacrolimus are potent immunosuppressants, which have improved survival after liver transplantation. We evaluated long-term renal function in children receiving calcineurin inhibitors after liver transplantation. A retrospective analysis of all children undergoing orthotopic liver transplantation (OLT) from 1989 to 1999 who survived 1-yr post-transplantation was performed. All received prednisolone and either cyclosporin and azathioprine or tacrolimus. Steroids were withdrawn at 3 months and cyclosporin/tacrolimus monotherapy was initiated 12 months post-OLT. Calculated glomerular filtration rate (cGFR) was calculated using the modified Counahan-Barratt formula and measured pretransplant, 3, 6 and 12 months post-transplant and annually thereafter. Data were analysed in a serial manner to evaluate the trend of cGFR over time selectively using the Wilcoxon signed rank test and paired t-tests as appropriate. A total of 113 patients (65 males:48 females) were followed up for more than 1 yr (maximum 5 yr). Median (range) age at transplantation was 26 months (3-177). There was a significant fall of 35% in cGFR at 3 months compared with the pretransplant value (p = 0.001). By 12 months following the reduction in immunosuppression dosage, renal function stabilized with a slight improvement in cGFR which reached 76% of the pretransplant value at 5 yr (p < 0.001). Children who were <1 yr of age at the time of OLT had better recovery of renal function than older children (p = 0.02). No association was seen with sex, the type of immunosuppression or the underlying diagnosis. Renal dysfunction is a known complication of CNI therapy. Despite an initial reduction in cGFR, which was associated with maximal immunosuppression, long-term low dose CNI therapy was not associated with continued deterioration of renal function, particularly in children who were transplanted as infants.     

Liver transplantation in children using non‐heart‐beating donors (NHBD)

Gozzini S, Perera MTPR, Mayer DA, Mirza DF, Kelly DA, Muiesan P, Sharif K. Liver transplantation in children using non‐heart‐beating donors (NHBD).
Pediatr Transplantation 2010: 14:554–557. © 2010 John Wiley & Sons A/S. Abstract: Selected livers from controlled NHBD are accepted for OLT in adults. Recent evidence has shown good medium‐term outcome. The purpose of this study was to report our experience of pediatric OLT with whole and partial grafts from NHBD, analyzing complications and outcome. Retrospective review of all the recipients who underwent primary OLT between December 2005 and December 2008, using livers from NHBD. Four children (one male child) mean age was 9.5 yr (0.2–17), mean weight was 26 kg (range 2.6–48), underwent OLT using NHBD. Mean donor age was 14.2 yr, and mean WIT (systolic BP <50 mmHg to cold perfusion) 12.2 min (range 10–15). Two children received reduced grafts and two full grafts. Mean cold ischemia time was 7.18 h (range 6–8). Liver function tests one wk and nine months post‐OLT confirmed a good graft function. One child was treated for two episodes of acute rejection. Post‐transplant complications included two cases of mild ischemic cholangiopathy treated conservatively. Graft and patient survival was 100% with a mean follow‐up of 19 months (range 8.1–43.4). Short‐ to medium‐term follow‐up suggests that liver grafts from young NHBD with short warm and cold ischemia times can be safely utilized in pediatric transplantation.     

Growth in children following liver transplantation

Although liver transplantation (OLT) has become standard therapy for end-stage liver disease in children, growth after OLT remains an area of concern. We reviewed our experience with growth after OLT at the Hospital for Sick Children in 83 patients who survived at least 1 yr post-transplant. Our aims were to describe the success rate in steroid cessation in patients after transplantation, to examine the effect of transplantation on subsequent growth, to see if steroid reduction had a beneficial effect on growth, and to quantify the risk of stopping steroids on rejection. Patients below age 5 yr were weaned off steroids more easily than those over age 5: 19.2% vs. 0% (p<0.05), 65.9% vs. 50%, and 79.5% vs. 37.5% (p<0.05) at post-transplant years 1, 2, and 3, respectively. Pre-transplant, 30% of patients were below the third percentiles for height and weight. Post-transplant, there was a steady improvement in the distribution of patients above the 3rd percentile, so that by post-transplant year 6, only 5% were below the 3rd percentile. Height and height velocity percentiles were found to correlate inversely with total yearly steroid dose (mg/kg) at post-transplant years 2, 3 and 6 (p<0.05). In 60% of patients, steroids were successfully discontinued. In these patients, height and height velocity percentiles have achieved a near normal distribution with 40% and 46% of patients above the 50th percentile for height and height velocity percentiles, respectively. No grafts were lost to rejection in those off steroids, and all rejection episodes were easily reversed. We conclude that the majority of children can be weaned off steroids successfully after OLT and that growth in those children in the presence of good graft function is near normal.     

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10–14 yr on background hepatitis B‐related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six‐yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6–15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B‐related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow‐up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever‐increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.     

Indications and outcome of liver transplantation in tyrosinaemia type 1

A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in !-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 7mol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. Conclusion Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.     

Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.     

Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience

Guiteau JJ, Cotton RT, Karpen SJ, O’Mahony CA, Goss JA. Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience.
Pediatr Transplantation 2010: 14: 326–331. © 2009 John Wiley & Sons A/S. Abstract: Treatment for HEH does not follow a standardized algorithm. From clinical experience, it is assumed that pediatric patients with HEH will fare as well as other common pediatric liver tumors post‐OLT. The UNOS dataset was examined for patients with pediatric OLT between 1987 and 2007. Patients were grouped into non‐tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using Fisher’s exact test. Patient, allograft, and recurrence‐free survival were compared using Kaplan–Meier curves and log‐rank tests. A total of 366 patients with pediatric OLT were identified with primary liver tumors (HB – 237, HCC – 58, HEH – 35, other – 36). HEH patient survival (five yr: 60.6%) was poorer than non‐tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence as a major cause in HB and HCC, but not for HEH or other liver tumors. The data suggest that patient survival may not be as high as previously believed and further investigation is warranted.     

Predictors of cost of liver transplantation in children: a single center study.

OBJECTIVE: Efforts to decrease the cost of orthotopic liver transplantation (OLT) must address the impact of specific interventions on clinical outcome. We hypothesized that an intervention designed to decrease the length of hospitalization would reduce costs without jeopardizing clinical outcome. We further sought to identify predictors of length of stay and cost for hospitalization after liver transplantation. METHODS: The study group included 47 children who underwent OLT from September 1996 to April 1999, and the control group included 36 children who underwent OLT from March 1994 to August 1996. The intervention was a transition to home program in which patients were discharged to a family living center when they met established clinical criteria and their families met predefined educational goals. We analyzed patients who survived 3 months after OLT. RESULTS: For the intervention group, the mean length of stay, total costs, and surgical costs were 29%, 36%, and 34% lower, respectively. Organ type, height z score, race, hepatic artery thrombosis, early allograft rejection, and participation in the transition to home program predicted length of stay and total costs. CONCLUSION: An early discharge program based on defined criteria can be used to decrease length of stay and cost after OLT without jeopardizing clinical outcome.     

Long-term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.     

Hepatic artery thrombosis in pediatric liver transplantation: Graft salvage after thrombectomy

Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re-transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (< 17 yrs of age) underwent liver transplantation. Three developed HAT (one a whole-liver graft recipient, age 17; two living-related graft recipients, ages 4 and 4.5 yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living-related patients, HAT was found incidentally during re-exploration for bleeding (day 2 and day 10). Thrombectomy was performed in all three patients. At 18-24 months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living-related recipients. One of these living-related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long-term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.