Functional outcomes of pediatric liver transplantation

The functional status and health-related quality of life (HRQOL) of children who survive liver transplantation (LT) have not been well documented. The purpose of this study was to determine the functional status and HRQOL in this population using a validated measure for children, the Child Health Questionnaire-Parent Form 50 (CHQ-PF50). METHODS: The CHQ-PF50 instrument was completed by the parents of 55 children who agreed to participate in a mailing survey. Subscale scores for the sample were compared with those of a published normal population (n = 391). RESULTS: Study sample characteristics were: 87% Caucasian, 54.5% female, mean age at survey was 9.6 years (range, 5-17 years). Responding caregivers were 95% biologic parents and 93% female. Compared with the normal population, LT recipients had lower subscale scores for general health perceptions (P < 0.0005), emotional impact on parents (<0.0005) and disruption of family activities (0.0005). The mean physical summary score of the LT recipients was lower than that of the normal population 48.1 +/- 12.1 (P = 0.005), but the mean psychosocial summary score was similar 48.8 +/- 11.9 (P = 0.156). Within the LT population, the original diagnosis (biliary atresia vs. other), type of LT (living donor vs. cadaveric), age at LT, z score for height, and hospital days did not significantly influence any of the subscale scores. CONCLUSIONS: Children who have survived LT have functional outcomes in the physical domain that are lower than those of normal children. Self-esteem and mental health in this group appeared normal. The parents in this sample experienced more emotional stress and disruption of family activities than did parents in a normal population.     

Barriers to access in pediatric living‐donor liver transplantation

Children receiving a LDLT have superior post‐transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well‐informed about LDLT but individuals with public insurance were significantly less likely to feel well‐informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT.     

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.     

Thrombotic events after pediatric liver transplantation

Ooi CY, Brandão LR, Zolpys L, De Angelis M, Drew W, Jones N, Ling SC, Fecteau A, Ng VL. Thrombotic events after pediatric liver transplantation.
Pediatr Transplantation 2010: 14:476–482. © 2009 John Wiley & Sons A/S. Abstract: TE may contribute to morbidity and mortality after LT. The objectives were to determine the incidence of early TE post‐pediatric LT and compare differences between children with and without TE. A retrospective review of 88 transplanted children (January 2002–October 2007) was performed to determine the incidence of Doppler‐confirmed DVT and ATE in the first month post‐LT. Fourteen (16%) patients developed TE: DVT in seven (8%) and ATE in seven (8%) patients. Six of 88 (6.8%) developed symptomatic CVL‐related DVT. Median (range) time post‐LT to DVT and ATE were 7 (4–18) and 8 (1–31) days, respectively. There was no significant difference in age/body weight at LT between patients with or without DVT and ATE. There was no significant difference between patients with or without HAT in age and weight at LT, cold ischemic time, duration of surgery, hematocrit levels, whole‐organ graft type, intraoperative FFP, high‐risk CMV status, or early acute cellular rejection. In conclusion, the incidence of early TE post‐pediatric LT was 16%, including DVT in 8%. Prospective studies are necessary to evaluate the role of prophylactic anticoagulation and potential modifiable risk factors post‐pediatric LT.     

Prope tolerance after pediatric liver transplantation

pT, under mono‐ and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS‐related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus‐based regimens (median follow‐up post‐LT: 6.0 yr, range: 0.8–9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow‐up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus–steroid regimen. Beyond April 2001, 105 patients received steroid‐free tacrolimus–basiliximab or tacrolimus–daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS‐free operational tolerance (n = 6), 27 of them belonging to the 43 steroid‐free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid‐free tacrolimus‐based IS seems to promote long‐term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.     

Transient hyperphosphatasemia after pediatric liver transplantation

BACKGROUND: Transient hyperphosphatasemia of infancy and early childhood is characterized by transiently increased serum activity of alkaline phosphatase (ALP), predominantly its bone or liver isoform, in children under 5 years of age. There is little information on the rate of transient hyperphosphatasemia in pediatric liver transplant recipients. METHODS: Patients who underwent liver transplantation at Ege University Organ Transplantation and Research Center, Izmir, Tureky, between January 1998 and January 2005, were included in the study. A total of 70 paediatric liver recipients' medical records were analyzed retrospectively. RESULTS: Transient isolated hyperphosphatasemia was observed in two of 70 patients and the rate of transient hyperphosphatasemia was estimated to be 2.8% in pediatric liver transplant recipient. Diarrheal episode was noted prior to the peak ALP activity in both cases. In one case the causative agent was not found, whereas in the other case Rotavirus was detected in a stool specimen. ALP activity normalized at 4 months and 18 days in the first and second cases, respectively. They continue follow up at the outpatient clinics with stable graft function. CONCLUSION: It is important to know that very high ALP levels can be seen without underlying significant pathology and the benign nature of the condition to avoid unnecessary investigations.     

儿童肝脏移植术后感染现状分析

自1989年首例儿童活体肝脏移植手术成功以来,肝脏移植术逐渐成为治疗儿童终末期和代谢性肝脏疾病的有效手段.近20年来,随着外科技术的日益完善及免疫抑制剂的合理应用,儿童肝脏移植术后的短期、长期存活率明显提高,但感染仍是肝脏移植术后最常见的并发症,严重影响预后.该文对儿章肝脏移植术后感染现状及合理用药作一概述.     

Linear growth after pediatric liver transplantation.

To determine growth patterns in a large cohort of unselected children undergoing liver transplantation, the outcomes of 294 orthotopic liver transplantations performed in 221 children at The University of Chicago between October 1984 and October 1992 were retrospectively reviewed; 66% were alive at the time of this analysis. The mean age at transplantation was 4.1 +/- 5.0 years; 44% of the children were male and 16% of the transplants were from living-related donors. The mean height z score at the time of transplantation was -1.6 +/- 1.8, and 39% of children had height z scores of < -2.0 at transplantation. When children with growth retardation at the time of transplantation (height z scores of < -2. 0) were compared with children with more normal growth, there were no significant differences in gender or re-transplantation rates, although children with growth retardation at transplantation were significantly younger than those with more appropriate growth (2.8 +/- 4.1 years vs 4.7 +/- 5.1 years, P <.05). The height z score of all children with biliary atresia at the time of transplantation was -1.9 +/- 1.7 compared with -1.2 +/- 2.0 in those children with underlying diseases other than biliary atresia. Catch-up growth was seen in 37% to 47% of children at any given time point after transplantation. Children with evidence of catch-up growth (growth velocity z score >0) 2 years after transplantation were more likely to be first-time transplant recipients, had more growth retardation at the time of transplantation, and were receiving lower doses of prednisone at 2 years after transplantation. Younger children were most likely to demonstrate catch-up growth after transplantation. In summary, a large proportion of children have growth retardation at the time of liver transplantation. This growth retardation is inversely correlated with age. Before transplantation, children with biliary atresia grow less well than children with other forms of liver disease. Up to one half of children demonstrate catch-up growth after liver transplantation. Growth after transplantation is proportional to the degree of growth retardation at transplantation and inversely correlated to age at transplantation. Children with poor growth after transplantation are more likely to be receiving higher doses of corticosteroid.     

Development of autoantibodies after pediatric liver transplantation

Dn‐AIH is a long‐term complication after LT. The aim of this study was to analyze the occurrence of autoantibodies in pediatric recipients and the clinical significance. From 1992 to 2008, 96 pediatric LT for non‐autoimmune liver diseases were performed in 94 children in our institution. Serum autoantibodies were checked in 68 subjects (73.9%). A positive autoantibody was defined as titers ≥1:40 for ANA, or ≥1:20 for ASMA, anti‐LKM, and AMA. Autoantibodies were detectable in 51 of 68 patients (75.0%). There was positivity for ANA in 30 patients, ASMA in 32, and AMA in three, while anti‐LKM was all negative. Immunosuppressive treatment with CsA, more than one episode of rejection, and abnormal ALT were risk factors for the development of autoantibodies. The incidence of the development of autoantibodies was 75.0% in pediatric LT cases in this study. ASMA was the most commonly found autoantibody. Autoantibodies may not play a sentinel role for dn‐AIH after LT.     

Devastating outflow obstruction after pediatric split liver transplantation

Sakamoto S, Nakazawa A, Shigeta T, Uchida H, Kanazawa H, Fukuda A, Karaki C, Nosaka S, Kasahara M. Devastating outflow obstruction after pediatric split liver transplantation. Abstract: HVOO is a rare complication after pediatric LT, which may lead to graft failure. There are various causes of HVOO, such as mechanical anastomotic obstruction and SOS. A 10‐month‐old female underwent split LT from a deceased donor for ALF. Her postoperative course was uneventful. However, her liver function suddenly deteriorated a month later. A liver biopsy revealed centrilobular injury, and D‐US suggested outflow obstruction. Venography was performed to reveal hepatic venous narrowing inside the graft. She received another graft from a living donor because of progressive graft failure in spite of successful venoplasty with stent insertion. The macroscopic findings of the explanted graft did not show an anastomotic stricture of the hepatic vein, although the pathological findings revealed necrosis of the first graft due to SOS. SOS might cause severe consequences with concomitant mechanical outflow obstruction after pediatric LT.     

Outcome of bowel perforation after pediatric liver transplantation

Abstract:  Bowel perforation is one of the causes of mortality after pediatric liver transplantation. The aim of this study was to evaluate the incidence, risk factors, clinical presentations, and outcomes of bowel perforation in pediatric liver recipients. This is a retrospective analysis of all pediatric patients who underwent liver transplantation at a single liver transplant center in Iran between 1999 and 2006. During this period 72 liver transplantations were performed in children <18 yr. Twenty-two children underwent 33 re-explorations after liver transplantation. Five bowel perforations occurred in four children (incidence, 6.9%). One patient required two re-explorations. The median time between liver transplantation and the diagnosis of the bowel perforation was seven days. All patients had abdominal distention before re-exploration. The sites of perforation were jejunum (n = 3) and ileum (n = 2), and simple repair was performed in all cases. Three children had a history of prior Kasai operation. One of them received high dose of methylprednisolone before bowel perforation. Two children expired after bowel perforation (mortality rate, 50%). Bowel perforation is relatively frequent after pediatric liver transplantation. Among risk factors, prior Kasai operation may have a role. We observed that abdominal distention is a sign of bowel perforation and a high index of suspicion is required for rapidly diagnosis of this complication. The outcome of bowel perforation is poor and its mortality is high. Further studies are needed to establish real risk factors for this complication.     

Patterns of infection after pediatric liver transplantation.

OBJECTIVE. To characterize the patterns of infection that occur after orthotopic liver transplantation in children. DESIGN. Inception cohort, retrospective. SETTING. Referral center for liver transplantation, university hospital. PATIENTS. Thirty-six consecutive children who underwent orthotopic liver transplantation and who survived for at least 48 hours after transplantation. INTERVENTIONS. None. MEASUREMENTS AND RESULTS. Twenty-six (72%) of the children had at least one infection, and infection caused four deaths. More infections occurred when prophylactic antilymphocyte antibodies were given than when they were not given (2.9 vs 1.0 infections per transplant). The risk of infection was greatest during the first 2 weeks after orthotopic liver transplantation. Most infections were caused by bacteria (52 cases), followed by viruses (16 cases) and fungi (11 cases). Bacteria were the most common pathogens during all periods, except the third and fourth weeks, when viruses predominated. The most common primary sites of bacterial infection were abdomen (15 cases), bloodstream (15 cases), and surgical wound (10 cases); the most frequent isolates were aerobic gram-negative bacilli (48% of isolates) and enterococci (19%). Cytomegalovirus was the most common viral pathogen (seven cases), and Candida albicans caused all fungal infections. Fungal infections were significantly associated with systemic antibiotic therapy and abdominal complications. CONCLUSIONS. Characteristic patterns of infection occur after pediatric orthotopic liver transplantation, and knowledge of these patterns is likely to result in improved care for transplant recipients.     

Bowel perforation after pediatric living donor liver transplantation

Purpose

Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department.

Patients and methods

The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B).

Results

Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p?<?0.01). Duration of surgery was an independent risk factor (p?=?0.05).

Conclusion

Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long.     

Cognitive and emotional outcome after pediatric liver transplantation

The aim of the study was to evaluate the cognitive and emotional development after pediatric liver transplantation. A total of 21 patients, aged 4-16.9 yr (median 9.6 yr) were tested 1-9 yr (median 4.2 yr) after the transplantation. The pretransplant diagnoses included biliary atresia (eight patients), various metabolic diseases (n = 6), acute liver failure (n = 3), and miscellaneous (n = 4). The cognitive functions were tested with Wechsler preschool and primary scale of intelligence (WPPSI)-R or Wechsler intelligence scale for children (WISC)-III according to age. The Piers-Harris self-concept scale and the evaluation of human figure drawings according to Koppitz were used to detect emotional problems. All tests in all patients were performed by the same psychologist. A significantly lower result on cognitive tests was seen when compared with the expected normal values (p < 0.01). The number of patients with results within or under the lower normal range was higher than expected. Although the mean value of the Piers-Harris self-concept scale was normal, there was a large spread within the group. Indicators of emotional problems were found in the human figure drawings of 50% of the patients. To some extent, low cognitive scores coincided with low scores on self-concept scale and indicators of emotional difficulties. We conclude that the high degree of cognitive and emotional problems after liver transplantation is an important argument for routine psychologic follow-up and support in these patients.     

Real-time and Doppler US after pediatric segmental liver transplantation

BACKGROUND: Accurate diagnosis of hepatic vein (HV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity because it allows unnecessary biopsy, obstruction or thrombosis and loss of the graft to be avoided. OBJECTIVE: To evaluate CD-US parameters to predict HV stenosis after segmental liver transplantation in children. MATERIALS AND METHODS: Retrospective review of 79 CD-US examinations measuring velocity at the HV anastomosis (HV1) and the main trunk 1-2 cm proximal to the HV/IVC anastomosis (HV2), the HV1/HV2 ratio and the spectral waveform of HV2. The study group comprised patients with stenosis confirmed by angiography. The control group comprised patients with a good clinical outcome. RESULTS: HV stenosis was seen in 12 CD-US examinations. The mean HV1/HV2 ratio was higher in the study group (6.0 versus 4.0). An HV1/HV2 ratio of >4.1 was predictive of HV stenosis (sensitivity 83%, specificity 76%). CONCLUSION: An HV1/HV2 ratio of >4.1 is a highly predictive CD-US parameter for the detection of hemodynamically significant HV stenosis on angiography.     

Predicting ideal outcome after pediatric liver transplantation: An exploratory study using machine learning analyses to leverage Studies of Pediatric Liver Transplantation Data

Machine learning analyses allow for the consideration of numerous variables in order to accommodate complex relationships that would not otherwise be apparent in traditional statistical methods to better classify patient risk. The SPLIT registry data were analyzed to determine whether baseline demographic factors and clinical/biochemical factors in the first‐year post–transplant could predict ideal outcome at 3 years (IO‐3) after LT. Participants who received their first, isolated LT between 2002 and 2006 and had follow‐up data 3 years post–LT were included. IO‐3 was defined as alive at 3 years, normal ALT (<50) or GGT (<50), normal GFR, no non‐liver transplants, no cytopenias, and no PTLD. Heat map analysis and RFA were used to characterize the impact of baseline and 1‐year factors on IO‐3. 887/1482 SPLIT participants met inclusion criteria; 334 had IO‐3. Demographic, biochemical, and clinical variables did not elucidate a visual signal on heat map analysis. RFA identified non‐white race (vs white race), increased length of operation, vascular and biliary complications within 30 days, and duct‐to‐duct biliary anastomosis to be negatively associated with IO‐3. UNOS regions 2 and 5 were also identified as important factors. RFA had an accuracy rate of 0.71 (95% CI: 0.68‐0.74), PPV = 0.83, and NPV = 0.70. RFA identified participant variables that predicted IO‐3. These findings may allow for better risk stratification and personalization of care following pediatric liver transplantation.     

Real-time and Doppler US after pediatric segmental liver transplantation

Background Accurate diagnosis of portal vein (PV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity by avoiding unnecessary biopsy, PV hypertension, thrombosis and loss of the graft. Objective To evaluate CD-US parameters for the prediction of PV stenosis after segmental liver transplantation in children. Materials and methods We retrospectively reviewed 61 CD-US examinations measuring the diameter at the PV anastomosis, velocities at the anastomosis (PV1) and in the segment proximal to the anastomosis (PV2), and the PV1/PV2 velocity ratio. The study group comprised patients with stenosis confirmed by angiography and the control group comprised patients with a good clinical outcome. Results PV stenosis was seen in 12 CD-US examinations. The mean PV diameter was smaller in the study group (2.6 mm versus 5.7 mm) and a PV diameter of <3.5 mm was highly predictive of stenosis (sensitivity 100%, specificity 91.8%). Conclusion A PV diameter of <3.5 mm is a highly predictive CD-US parameter for the detection of hemodynamically significant stenosis on angiography.