Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages less than 1, 1-5 and greater than 5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight less than -1 was 57%, greater than -1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 +/- 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.     

Long-term nutritional and neurodevelopmental outcome of liver transplantation in infants aged less than 12 months

BACKGROUND: Liver transplantation is established treatment for children with end-stage liver disease and has a 5-year survival rate of 80% to 85%, even in infants under 12 months. Long-term outcome in nutritional rehabilitation and normal development is unknown. This study aimed to prospectively evaluate growth and psychoneurologic performance of children who undergo liver transplantation in infancy. METHODS: Twenty-five infants (18 girls, 7 boys) who underwent liver transplantation at less than 12 months of age (median age, 9 months) were evaluated for 4 years. Growth measurements were expressed as standard deviation scores (SDSs; mean +/- SEM), and psychoneurologic performance was assessed with the unrevised Griffiths Mental Ability Scales (normal range, 80-120). RESULTS: Four children died during the study (4-year survival, 84%). The children were malnourished before transplantation (SDSs: weight, -1.9 +/- 0.2; midarm muscle area, -0.93 +/- 0.3; midarm fat area, -1.52 +/- 0.3; and height, -0.95 +/- 0.3). Nutritional rehabilitation for all parameters occurred within 12 to 24 months after transplantation, which was most significant for weight (-1.1 +/- 0.2, P = 0.001), midarm muscle area (0.74 +/- 0.3, P = 0.001), and midarm fat area (-0.44 +/- 0.3, P = 0.01). There was some improvement in height (-0.72 +/- 0.3, P = 0.14), which was not significant, although infants who were severely stunted before transplantation (mean height standard deviation score [SDS] -2.46) showed significant catch-up at 1 year after transplantation (mean height SDS -1.2, P = 0.003). Psychoneurologic scores were within normal limits before transplantation and were maintained for the 4-year follow-up period, although individual scores varied during this period. Improved nutritional status was associated with increased muscle bulk and subsequent improvement in motor scores from 90.6 at initial assessment to 97.3 at 4 years (P = 0.28). There was a temporary reduction in social skills and eye-hand coordination in the first year, which may have been an effect of the hospital environment or cyclosporine immunosuppression. Language abilities also regressed during the first year, possibly related to the effect of nasogastric tube feeding in delaying normal speech development. CONCLUSIONS: Liver transplantation in infancy has not only a successful outcome but is also associated with long-term catch-up growth and nutrition and maintenance of normal development.     

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.     

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.     

Successful immune response to a recombinant hepatitis B vaccine in children after liver transplantation

BACKGROUND: Patients who undergo liver transplantation require multifaceted general care, and vaccination has a fundamental role before and after transplantation. The purpose of this study was to provide a prospective evaluation of the immunogenicity of the recombinant vaccine (RV) against Hepatitis B in pediatric patients with liver transplants (TxH) who for different reasons did not receive a pretransplantation vaccine. METHODS: From June 1996 to December 1999, 47 pediatric patients with liver transplants were vaccinated with RV. Patients older than 1 year of age, in stable condition, and 6 months post-transplantation were included. The vaccination scheme was 0-1 and 6 months, intramuscular 10 microg in less than 30 kg body weight, and 20 microg in more than 30 kg body weight. The nonresponder patients were vaccinated with a booster dose and a double dose 1 to 6 months after the last dose. Responders to titer HBs Ab enzyme immunoassay (EIA) <10 UI/ml were defined as nonresponders, to titer between 10-100 UI/ml as responders, and to higher titer of 100 UI/ml as high responders. RESULTS: The following data were obtained from the 47 patients: mean +/- standard deviation (SD) age at vaccination was 10.76 +/- 5.96 years old and the mean +/- SD post-transplant time at the beginning of vaccination was 3.56 +/- 2.19 years. Thirty-three of 47 patients (70%) responded to doses according to body weight, and 14 (30%) did not respond, necessitating a booster dose after which 7 responded (50%). The global seroconversion was 85%. There was not a significant responder cyclosporine concentration dosage (154 vs. 150 ng/ml) difference between responders and nonresponders. Sixty-six percent (8 of 12) of patients receiving a triple immunosuppressive scheme (cyclosporine, steroids, and Azathioprine) had a positive response, while 84% (16 of 19) receiving a double scheme (cyclosporine and steroids) and 100% (16 of 16) receiving monotherapy with cyclosporine had a positive response. By comparing a triple scheme with monotherapy, the Fisher exact test found a P < 0.01. Incidence of adverse effects (local pain) was 2.63%. CONCLUSION: Immunization with RV was well-tolerated with acceptable seroconversion and safety in recipients after liver transplantation, particularly in those undergoing cyclosporine monotherapy. The population studied showed better results than did other populations of immunosuppressed patients.     

Neuropsychological outcome of pediatric liver transplantation

Children with end-stage liver disease who undergo liver transplantation may have unrecognized neuropsychological and academic deficits, for which remediation programs may be available. Intellectual, academic, and neuropsychological measures of 28 pediatric patients who had received successful liver transplantation at least 1 year previously were compared with those of 18 patients with cystic fibrosis (to control for effects of growth retardation and chronic illness) matched for age, age at diagnosis, physical growth, and parents' socioeconomic status. Liver transplant patients had significantly lower scores on nonverbal intelligence tests (mean +/- SD for liver transplant vs cystic fibrosis patients: 89.1 +/- 19.1 vs 105.8 +/- 17.6), lower academic achievement, and lower zeta scores for age in the areas of learning and memory (-0.68 +/- 1.09 vs 0.19 +/- 1.24), abstraction and concept formation (-1.73 +/- 1.58 vs -0.79 +/- 1.37), visual-spatial function (-0.66 +/- 1.09 vs 0.10 +/- 0.69), and motor function (-0.13 +/- 0.85 vs 0.36 +/- 0.57). No differences were found on tests of verbal intelligence, or in alertness and concentration, perceptual-motor, and sensory-perceptual areas. Cyclosporine levels were found to correlate positively with motor speed (r = .41, P less than .05). Thorough psycho-educational and neuropsychological evaluations should be considered for pediatric patients who receive liver transplantation to allow these children to maximize their potential.     

Body composition and components of energy expenditure in children with end-stage liver disease

BACKGROUND: Better understanding of body composition and energy metabolism in pediatric liver disease may provide a scientific basis for improved medical therapy aimed at achieving optimal nutrition, slowing progression to end-stage liver disease (ESLD), and improving the outcome of liver transplantation. METHODS: Twenty-one children less than 2 years of age with ESLD awaiting liver transplantation and 15 healthy, aged-matched controls had body compartment analysis using a four compartment model (body cell mass, fat mass, extracellular water, and extracellular solids). Subjects also had measurements of resting energy expenditure (REE) and respiratory quotient (RQ) by indirect calorimetry. Nine patients and 15 control subjects also had measurements of total energy expenditure (TEE) using doubly labelled water. RESULTS: Mean weights and heights were similar in the two groups. Compared with control subjects, children with ESLD had higher relative mean body cell mass (33 +/- 2% vs 29 +/- 1% of body weight, P < 0.05), but had similar fat mass, extracellular water, and extracellular solid compartments (18% vs 20%, 41% vs 38%, and 7% vs 13% of body weight respectively). Compared with control subjects, children with ESLD had 27% higher mean REE/body weight (0.285 +/- 0.013 vs 0.218. +/- 0.013 mJ/kg/24h, P < 0.001), 16% higher REE/unit cell mass (P < 0.05); and lower mean RQ (P < 0.05). Mean TEE of patients was 4.70 +/- 0.49 mJ/24h vs 3.19 +/- 0.76 in controls, (P < 0.01). CONCLUSIONS: In children, ESLD is a hypermetabolic state adversely affecting the relationship between metabolic and nonmetabolic body compartments. There is increased metabolic activity within the body cell mass with excess lipid oxidation during fasting and at rest. These findings have implications for the design of appropriate nutritional therapy.     

Somatic growth in infant heart transplant recipients

Infant heart transplantation is now entering its second decade of clinical experience. To understand better issues relating to somatic growth, this retrospective study will describe growth patterns in a group of infant heart transplant recipients. Early growth: growth velocity from birth to transplantation in 77 infants transplanted before 6 months of age was compared with growth velocity from transplant to 3 months. Growth from 3 to 6 months and from 6 to 12 months after transplantation is described. Growth velocities (mean +/- SD) for weight (g/d) and length (cm/yr) for these 4 time periods respectively were: 7+/-14 and 27+/-22, 32+/-9 and 35+/-14, 17+/-7 and 24+/-10, 12+/-6 and 17+/-8. Growth velocities for both weight (p<0.01) and length (p = 0.04) were significantly improved in the first 3 months after transplantation. Late growth: Growth beyond 5 yr post-transplantation was described in a group of 51 infants transplanted in the first year of life and who survived at least 5 yr (median 6.8 yr, range 5.0 to 10.9). Most recent growth parameters (z-score; mean +/- SD) were: weight -0.55+/-1.2, height -0.48+/-0.97 and weight for height -0.16+/-0.96. Factors (with significant p-values) evaluated for their possible influence on late height (<5th percentile vs. > or =5th percentile) were: age at transplant, hospital days from transplant to discharge, hospital days 1st year after transplantation (p = 0.019), hospital days after 1st year, rejection episodes 1st year, rejection episodes 1-5 yr (p = 0.02) mid-parental height (p = 0.008) and isotopic glomerular filtration rate (p = 0.055). Conclusion: Growth while awaiting infant heart transplantation is poor, but adequate catch-up growth does occur. Beyond 5 yr most (88%) infant heart transplant recipients have weight and height in the normal range. Early illness, late rejection and genetic growth potential may play the largest role in later height attainment.     

Evaluation of catch-up growth after liver transplantation in children with biliary atresia

Orthotopic liver transplantation (Tx) has improved survival in infants with extrahepatic biliary atresia (BA) when portoenteroanastomosis fails. Symptoms leading to Tx include liver failure, poor quality of life and growth failure. The objective of the study was to determine catch-up growth in children with BA. Medical records and growth data of 36 patients (24 girls) who received a Tx due to BA were analyzed. Thirty-two patients completed 3 yr and 15 patients 7 yr of follow-up after Tx. At Tx, the median age was 2.7 yr (range 0.7-12.6) and mean height Z score (+/-s.d.) was -1.56 (+/-1.3). Patients were divided in two groups according to age at Tx: group I (n = 10), younger than 1.0 yr, and group II (n = 26) older than 1.0 yr. Median age (range) at Tx in group I was 0.8 yr (0.7-1.0) and in group II it was 3.35 yr (1.25-12.6). Thirteen patients (nine in group I) were receptors of living related donors. We evaluated linear growth, liver and renal function, immunosuppressive regimen and allograft rejection episodes. We did not find any significant differences in allograft or renal function, immunosuppressive therapy and number of acute rejection episodes or height Z score at Tx, second and third year post-Tx between both groups. The mean height Z score at Tx in group I was -1.61 and in group II -1.54; at the second year, group I -0.66 and group II -1.08; at the third year, group I -0.17 and group II -0.85; and at the seventh year (total group) -0.3. However, the height gain at the third year was better in group I than in group II (p < 0.01, t-test). Height Z score at the third year improved more than 1 SDS in seven out of eight patients in group I and in only nine out of 24 in group II (odds ratio 11.6). We also found a correlation between height gain at the third year and age at Tx (r-0.65) and between height gain at the third year and height Z score at Tx (r-0.54) (Pearson, p < 0.05). Children with BA who are transplanted before 12 months of age presented better catch-up growth without change survival and morbidity. Orthotopic liver Tx improves survival and also enables height gain in these children.     

Surgery of liver tumors in children in the last 15 years.

AIM: Aim of the study was to review our experience in the management of liver tumors in children over the last 15 years. PATIENTS AND METHODS: A cohort of 78 children with liver tumors managed in our institution between 1991 and 2006 was retrospectively reviewed. There were 45 males and 33 females with a mean age of 32 +/- 41 months at diagnosis. Most tumors were malignant (n = 57); the most frequently occurring tumor was hepatoblastoma (n = 47), followed by hepatocarcinoma (n = 5), sarcoma (n = 4), and lymphoma (n = 1). Vascular tumors (n = 12) predominated among the benign tumors followed by mesenchymal hamartoma (n = 4), focal nodular hyperplasia (n = 3), adenoma (n = 1), and inflammatory pseudotumor (n = 1). We reviewed the epidemiologic features, clinical presentation, diagnosis, treatment and outcomes. We employed MRI and angio-CT for SIOPEL PRETEXT staging and selected the management accordingly for malignant tumors. We analyzed the long-term survival using Kaplan-Meier curves. RESULTS: Benign tumors had an excellent outcome with both medical or surgical management. Of the malignant tumors 4 were PRETEXT I and were treated by left lateral segmentectomy with 100 % survival; 20 were PRETEXT II (12 left and 8 right lobe) and were treated by lobectomy of the corresponding side, except for 1 case which required OLT (90 % survival); 9 children had PRETEXT III tumors requiring trisegmentectomy or extended lobectomies with OLT in 1 case (77.7 % survival). Fourteen children had PRETEXT IV tumors: 10 received OLT and 9 of them are still alive (64.2 % survival). Overall survival was 80.8 %, and actuarial survival at 6 years was 82.2 %. Other malignant tumors had variable results. CONCLUSIONS: Outcomes have improved much in the last years. Surgical removal is necessary in most cases. Transplantation is a very useful adjunct. Treatment of these tumors should be concentrated in centers with expertise.     

The outcome of renal transplantation in children without prolonged pre-transplant dialysis

Controversy in the literature exists over whether or not it is beneficial to maintain a patient on dialysis for a prolonged time before transplantation. Because no data exist comparing children who have had prolonged dialysis before transplantation to those who have none, we reviewed the charts of all children transplanted at the Children's Hospital of the Cleveland Clinic Foundation. Of those, we selected three groups for analysis: group one (n = 12) consisted of patients who had had less than or equal to 10 weeks of dialysis before transplantation (6.8 +/- -2.2 weeks, +/- = SD); group two (n = 21) were patients who had had more than 10 weeks of dialysis (142 + +/- -148 weeks). Both groups had two years of follow-up data. Group three (n = 13) consisted of patients who had had less than two years of follow-up (18.7 +/-/-7 months) but no dialysis before transplantation. There were no differences in mode of dialysis between groups one and two nor in the type of transplant (living-related donor vs. cadaveric). Significantly, the patients in group three received more cyclosporine A and less anti-lymphocyte globulin than the other two groups (p less than 0.05). Patients in group two received more transfusions (11.9 +/- 14.3) than patients in group one (4.0 +/- 2.7) and group three (3.5 +/- 7.3). There were no differences in number of patients who experienced at least one rejection episode among the three groups. Although the mean serum creatinine concentration at two years of follow-up was higher in group two (3.6 +/- -3.9 mg/dl), this was not significantly different from group one (1.7 +/- -0.7 mg/dl) or group three (1.9 +/- -0.5, n = 7). Sixty-three percent of patients in group one, 60% of patients in group two and 91% in group three had functioning allografts at two years follow-up. Although there may be other considerations, our data do not indicate any increase in rejection or decrease in graft survival in children who do not receive prolonged dialysis.     

Survival from acute non-lymphocytic leukaemia, 1971-88: a population based study

Survival rates were studied among 1258 children with acute non-lymphocytic leukaemia diagnosed in 1971-88 and included in the population based National Registry of Childhood Tumours. Of the total, 147 (12%) died without receiving treatment. Among the remaining treated children, actuarial five year survival rates were 6% in 1971-4, 15% in 1975-9, 23% in 1980-3, and 40% in 1984-8. Infants aged less than 1 year had a significantly worse prognosis and there was a significant trend towards lower survival rates with increasing white cell count. No independent significant effects on survival were found with sex, French-American-British (FAB) subtype, or the presence or absence of Down's syndrome. Children entered in national trials had a higher survival rate than those who were not entered, and children treated at teaching hospitals had a higher survival rate than those who were treated elsewhere. Among the 535 (43%) children who survived at least one year from diagnosis no factor studied had a significant effect on survival, emphasising the importance of achieving first remission as a determinant of long term survival.     

The current status of pediatric liver transplantation in Mainland China

Zhou J, Shen Z, He Y, Zheng S, Fan J. The current status of pediatric liver transplantation in Mainland China.
Pediatr Transplantation 2010: 14:575–582. © 2010 John Wiley & Sons A/S. Abstract: The aim of this article is to study the current status of pediatric liver transplantation in Mainland China. A total of 337 cases of pediatric liver transplantation enrolled in CLTR between 1993 and May 2009 were analyzed retrospectively. The median transplant age was 8.7 yr (64 day–17.8 yr), and Wilson’s disease was the most common indication (35.4%). Liver transplantation for biliary atresia accounted for 49.3% and 54.2% in 2008 and 2009 and had become the most common indication nowadays. One‐ and three‐yr survival rates of children transplanted at age<1 yr were 69.2% and 59.3%, respectively, and were significantly worse than those transplanted at age≥1 yr (83.9% and 76.6%, p < 0.05).In 63.8% (208/326) of the patients, LDLT was used with an overall one‐ and three‐yr survival rates of 87.5% and 84.4%, respectively. The one‐ and three‐yr survival for DDLT was significantly lower (66.7% and 52.2%, p < 0.05). The one‐ and three‐yr survival rates for those transplanted in era 1993–2000 were 63.6% and 36.4%, respectively, and the one‐ and two‐yr survival rates in the latest era (2007‐2009) were markedly improved (81.9% and 79.0%, p < 0.05). Cox’s analysis identified DDLT (HR = 2.90, CI 95% 1.5–5.6), being transplanted in era 1993–2000(HR = 3.4, CI 95% 1.1–10.2), fulminant liver failure (HR = 6.0, CI 95% 2.0–17.5), and malignancy (HR = 3.8, CI 95% 1.4–10.3) as predictors of increased mortality, and children transplanted at age 8–17 yr have an better survival (HR = 0.2, CI 95% 0.1–0.6). We concluded that pediatric liver transplantation is gradually developing and would probably be a promising therapy for pediatric end‐stage liver diseases in Mainland China.     

Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation

Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984–1990; 78.5% for biliary atresia (n =?286), 87.3% for metabolic diseases (n?=?59), and 72.7% for acute liver failure (n?=?22). The 5-year survival was 73.6% for the 209 children grafted in 1984–1990 and 85% for the 206 grafted in 1991–1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984–1990 to 10% in 1991–1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P?<?0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1?year of age at transplantation was 88.8% and 80.3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.     

Survival from acute non-lymphocytic leukaemia, 1971-88: a population based study.

Survival rates were studied among 1258 children with acute non-lymphocytic leukaemia diagnosed in 1971-88 and included in the population based National Registry of Childhood Tumours. Of the total, 147 (12%) died without receiving treatment. Among the remaining treated children, actuarial five year survival rates were 6% in 1971-4, 15% in 1975-9, 23% in 1980-3, and 40% in 1984-8. Infants aged less than 1 year had a significantly worse prognosis and there was a significant trend towards lower survival rates with increasing white cell count. No independent significant effects on survival were found with sex, French-American-British (FAB) subtype, or the presence or absence of Down's syndrome. Children entered in national trials had a higher survival rate than those who were not entered, and children treated at teaching hospitals had a higher survival rate than those who were treated elsewhere. Among the 535 (43%) children who survived at least one year from diagnosis no factor studied had a significant effect on survival, emphasising the importance of achieving first remission as a determinant of long term survival.     

Pediatric liver transplantation in Iran: evaluation of the first 50 cases

LT is nowadays accepted as the definitive therapy for end-stage liver disease. We report our experiences with pediatric LT using grafts from living related and DD. From April 1999 to March 2006, 50 infants and children who underwent LT were studied for pretransplantation status, medical and surgical complications and survival rate. There were 33 (66%) boys and 17 (34%) girls. The mean age of patients was 9.9 +/- 4.8 yr (range: 0.9-17.7) with a mean weight of 33.4 +/- 18.4 kg (range: 7.5-80). The main indications were cryptogenic cirrhosis (30%), autoimmune cirrhosis (24%), followed by biliary atresia (22%), Wilson disease (14%), progressive familial intrahepatic cholestasis (4%), fulminant hepatitis (4%) and tyrosinemia (2%). We used living-related donor in 14 (28%) and split liver in 5 (10%) cases and other patients received whole liver from DD. The mean follow-up of patients was 24.7 +/- 22.6 months (range: 1-72). The main postoperative complications were acute cellular rejection (44%) and infections (30%), whereas chronic rejection was seen in 26% of cases. The mortality rate was 24%. Overall mean survival (76% alive) was 63.5 +/- 5.7, 95% CI: 52.3-74.6. Our results demonstrate that pediatric LT is a feasible undertaking in Iran. Organ shortage in our area led to liberal use of living related and split liver techniques. The overall results of the pediatric LT in Iran are encouraging.     

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia.

Metabolic diseases (MD) are the second largest indication group for orthotopic liver transplantation (OLTx) in children after biliary atresia (BA). A better outcome after transplantation can be expected because of a better pretransplant condition and the absence of previous abdominal surgery. To prove this statement, patient survival, graft survival, and morbidity were compared between a group of 24 for MD and 52 for BA consecutively transplanted children. The actuarial one- and five-year patient survival rates for MD were 96% and 84%, and for BA 84% and 70%, respectively (p logrank test = 0.17). Three MD children (13%) and 15 BA children (29%) died. The actuarial one- and five-year graft survival rates for MD were 75% and 58%, and for BA 75% and 64%, respectively (p logrank test = 0.76). Seven MD children (29%) and 11 BA children (21%) were retransplanted. Postoperative bleeding and gastrointestinal complications occurred less frequent (4% vs. 18% and 4% vs. 14%, respectively), whereas biliary complications, viral infections, and acute rejection occurred more frequently (38% vs. 21%, 29% vs. 15%, and 50% vs. 37%, respectively) in MD children. The difference in the incidence of the various postoperative complications between both groups was not statistically significant. The mean ICU and ventilator stay was 7.5 and four days, respectively, in MD children and 16 and 10 days, respectively, in BA children (p = ns). The mean infection, complication, intervention, and retransplantation rate was equal in both groups. Conclusion: Mortality and morbidity after pediatric liver transplantation for MD and BA are not different despite the better starting point for children with MD.     

Fatty liver in obese children: prevalence and correlation with anthropometric measurements and hyperlipidemia

The aim of this study was to evaluate the correlation of ultrasonography-proven fatty liver with liver functions, serum lipid levels and anthropometric measurements in children with exogenous obesity. Three hundred and twenty-two patients (183 girls, 56.8%) with a mean age of 11.4+/-3.2 years (4-18 years) who presented with the complaint of obesity were enrolled. In 38 (11.8%) patients, increased liver echogenicity resembling fatty liver was found (Group 1). The body mass index percentages of group 1 patients were significantly higher than of those without fatty liver (Group 2) (157.7+/-18.0 vs 151.3+/-17.8, p=0.038). Alanine and aspartate aminotransferase levels of group 1 patients were significantly higher than of group 2 (p=0.002 vs p=0.028, respectively). Triglyceride levels were significantly higher in group 1 patients (120.8+/-88.8 vs 100.5+/-58.5 mg/dl, p=0.044). In conclusion, ultrasonography is an easy and noninvasive method for the diagnosis of fatty liver in children with obesity. Body mass index and serum lipids were higher in group 1 patients. The diagnosis and early treatment of obesity in childhood is important for the prevention and better treatment of related complications. Thus, ultrasonography should be a part of the early evaluation of obese children.     

The pediatric risk of mortality score in infants and children with fulminant liver failure

The pediatric risk of mortality (PRISM) score as a severity scoring system has never been assessed in infants and children with fulminant liver failure (FLF). A retrospective case study of 109 infants and children admitted in a 22-bed pediatric and neonatal intensive care unit of a tertiary university hospital, National Referral Center for Pediatric Liver Transplantation, from March 1986 to August 1997 was carried out. PRISM score was not significantly different within etiologic FLF categories, or between infants and children. However, PRISM score (mean +/- SD) showed significant difference (p = 0.001) between the 27 patients who spontaneously recovered with supportive care (8.8 +/- 5.0) and 82 patients who underwent emergency liver transplantation (ELT) or those who died before (14.9 +/- 7.7). PRISM score-based probability of mortality was underestimated when compared with observed mortality. A death probability higher than 20% had a 24% sensitivity and 95% specificity for severe outcome. Reciever operating characteristic curve for PRISM score showed elevated discriminative power (Az = 0.91) for discerning children with severe outcome from those who spontaneously recovered with supportive care. A PRISM score more than 10 showed an odds ratio of 2.69 for predicting severe outcome (95% CI: 1.11-6.55; p = 0.038). In conclusion, the PRISM score is an accurate means of severity assessment in pediatric FLF. However, PRISM score-based mortality was of low predictive value.