Transient elastography assessment of liver allograft fibrosis in pediatric transplant recipients

TE measures liver stiffness to assess fibrosis. Its use in post‐transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB‐4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007‐2018) were eligible. Ninety‐four patients (45%M) aged 1‐21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty‐nine percent received whole‐liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16‐33] IU/L. Twenty‐one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank‐sum test). APRI and FIB‐4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56‐0.85) with an optimal cut‐point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB‐4. TV grafts demonstrate similar correlation with histology as whole‐liver grafts.     

Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow‐up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non‐invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non‐invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100‐fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval ‐0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non‐invasive, reliable tool for the assessment of graft fibrosis in the follow‐up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.     

Detection of graft fibrosis by vibration‐controlled transient elastography in pediatric liver transplant recipients

Pediatric liver transplant recipients are at risk of developing graft fibrosis which can affect patient survival. VCTE is a non‐invasive tool that measures LSM and has been shown to correlate with hepatic fibrosis. The aim of this study was to therefore evaluate the ability of LSM to predict fibrosis in pediatric liver transplant recipients with different graft types. We performed a cross‐sectional study evaluating LSM of 28 pediatric liver transplant recipients who underwent a total of 20 liver biopsies within 1 month of LSM. LSM was compared to liver histology as well as graft type: WL or PL. The median LSM of all post‐transplant patients was 5.6 kPa (range = 2.7‐18.3). There was a statistically significant correlation between LSM and METAVIR fibrosis score (P = .001) and LAF score (P < .001). There was no difference in LSM between graft type (P = .088). The AUROC curve for LSM predicting any significant fibrosis (F ≥ 2) was 0.863. A cutoff value of 7.25 had a sensitivity of 71%, specificity of 100%, NPV of 87%, and PPV of 100% for significant fibrosis. LSM by VCTE is feasible in pediatric liver transplant recipients regardless of graft type. We found a significant correlation between LSM and hepatic fibrosis and established a cutoff value that may help determine which patients warrant further evaluation for graft fibrosis.     

Association of post‐transplant donor‐specific HLA antibody with liver graft fibrosis during long‐term follow‐up after pediatric liver transplantation

The aim of this study was to evaluate the significance of post‐transplant DSA as a predictor of liver fibrosis during long‐term follow‐up after pediatric LT. We evaluated the histological findings in 18 LT recipients who underwent liver biopsy after DSA screening. Liver fibrosis was scored based on the METAVIR fibrosis staging. Patients were divided into 2 groups based on histological findings, and clinical characteristics among patients with liver fibrosis were assessed. Of 18 patients, 7 were included in the fibrosis group. No significant between‐group differences were found regarding peritransplant characteristics, including age, sex, primary disease, ABO incompatibility, and immunosuppressive regimen. Episodes of acute rejection and non‐adherence to immunosuppressive drugs were comparable between both groups. The MFI for anti‐DR DSA and positive rate were significantly higher in the fibrosis group (1655 vs 216; P = .019, 86% vs 27%; P = .012, respectively). MFI for anti‐DQ DSA was higher in the fibrosis group, but non‐significantly (2052 vs 384; P = .46). Post‐transplant anti‐DR DSA is associated with graft fibrosis during long‐term follow‐up. This finding seems useful for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti‐DR DSA, after pediatric LT.     

The use of transient elastography and non‐invasive serum markers of fibrosis in pediatric liver transplant recipients

The use of non‐invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver‐transplanted children (60M, 8.9 [0.5–18.5] yr) and 336 healthy controls. Liver biopsy was available in 36 children. Results of histology and non‐invasive markers were compared using correlation coefficient or Mann–Whitney U‐test as appropriate. TE correlated best with histological degree of fibrosis (r = 0.85 vs. r = 0.04 [FT] or r = ?0.38 [ELF]). Liver stiffness values for transplanted children without fibrosis were significantly higher than those of healthy controls (7.55 [5.4–20.4] kPa vs. 4.5 [2.5–8.9] kPa). Presence of rejection was a potent confounder for the performance of TE. Both TE and FT reflected clinical changes (acute rejection, cholestasis, increasing fibrosis) in a total of 16 patients who underwent serial measurements. TE correlates better with histological degree of fibrosis in liver‐transplanted children than FT or ELF, but an individual baseline value needs to be determined for each patient. Normal or cutoff values for pathological degrees of fibrosis cannot be transferred from non‐transplanted children. Follow‐up studies, preferably with protocol biopsies, might help to improve the diagnostic quality of TE.     

Transforming growth factor beta 1 levels in the blood of pediatric liver recipients: Clinical and biochemical correlations

TGF‐β1 is a cytokine with profibrogenic and immunosuppressive activities, which suggest the clinical significance of TGF‐β1 for the assessment of graft function after LT. We analyzed the dynamics of TGF‐β1 levels in the blood after LDLT in 135 pediatric liver recipients and examined the relationship between the cytokine levels and the laboratory and clinical variables. We found that TGF‐β1 levels in the blood of patients with ESLD were lower than that in healthy children of the same age, P = .001. Moreover, blood levels of TGF‐β1 were associated with liver disease etiology (r = .23) and hepatic fibrosis severity (r = .33). Before LDLT, TGF‐β1 levels were significantly higher in children with good outcomes than in recipients who developed graft dysfunction early in the post‐transplant period, P = .047. One month after LDLT, TGF‐β1 levels in blood plasma increased in pediatric recipients, P = .002. Cytokine levels were significantly correlated with gender (r = .21) and HLA (r = ?.24) mismatches, as well as with TAC dosage (r = ?.32) later in the post‐transplant period. One year after LDLT, TGF‐β1 plasma levels were higher (P = .01) than those before LDLT and did not correlate with most of the investigated biochemical and clinical variables. Conclusion: Blood levels of TGF‐β1 are associated with hepatic fibrosis severity, graft dysfunction development, and TAC dosage and can be regarded as a potential prognostic biomarker for the assessment of graft function and the optimization of immunosuppressant dosage in pediatric recipients after LDLT.     

Pretransplant increases in left ventricular volume and mass are associated with QT prolongation during pediatric liver transplantation

Structural alterations in the cirrhotic heart may contribute to electromechanical abnormalities, represented by QT prolongation. The aim of this study was to investigate the changes in QTc according to the operative stage during pediatric LT and to identify which baseline echocardiographic parameters were associated with intraoperative QTc prolongation. Data were evaluated from 39 children undergoing LT for chronic liver disease (median age 9 months). In 19 patients (48.7%), baseline QTc was prolonged ≥440 ms (462 ± 19 ms). Through the period of post‐reperfusion, QTI, QTc, and JTI progressively increased, although values partially recovered toward the end of surgery. High LVMI (≥82.51 g/m²) was associated with baseline QTc ≥ 440 ms (OR = 1.034, P = .032). In the 5 minutes post‐reperfusion stage, marked QTc prolongation (defined as QTc ≥ 500 ms; n = 24, 61.5%) was significantly associated with high EDVI (OR = 1.060, P = .027) and SVI (OR = 1.075, P = .026). In children with chronic liver disease, increased ventricular volumes and mass may increase the risk of QTc prolongation during LT, suggesting that repolarization abnormalities might be contributed by structural changes characteristic of cirrhotic cardiomyopathy.     

Liver transplantation for urea cycle disorders in pediatric patients: A single‐center experience

LT has emerged as a surgical treatment for UCDs. We hypothesize that LT can be safely and broadly utilized in the pediatric population to effectively prevent hyperammonemic crises and potentially improve neurocognitive outcomes. To determine the long‐term outcomes of LT for UCDs, charts of children with UCD who underwent LT were retrospectively reviewed at an academic institution between July 2001 and May 2012. A total of 23 patients with UCD underwent LT at a mean age of 3.4 yr. Fifteen (65%) patients received a whole‐liver graft, seven patients (30%) received a reduced‐size graft, and one patient received a living donor graft. Mean five‐yr patient survival was 100%, and allograft survival was 96%. Mean peak blood ammonia (NH₃) at presentation was 772 μmol/L (median 500, range 178–2969, normal <30–50). After transplantation, there were no episodes of hyperammonemia. Eleven patients were diagnosed with some degree of developmental delay before transplantation, which remained stable or improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at long‐term follow‐up. LT was associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved neurocognitive development. Long‐term follow‐up is underway to evaluate whether LT at an early age (<1 yr) will attain improved neurodevelopmental outcomes.     

Outcomes of liver transplantation in pediatric recipients with cardiovascular disease

LT exerts considerable stress on the heart perioperatively. Limited data exist on impact of cardiovascular diseases on LT children. This study evaluated the outcomes of children with CVD who underwent LT and compared with pretransplant findings. From 518 LT recipients, 82 (15.8%) had CVD. Sixty patients were classified as low‐risk adjustment for congenital heart surgery 1 (RACHS 1 and 2). Five patients were classified as RACHS ≥3. The most common echocardiographic finding in the CVD patients (25/82) was ASD. CVD patients had more abnormal EKG (32.4% vs 14.5%, P < .001), abnormal chest X‐ray (11.8% vs 1.4%, P < .001), and altered echocardiography (89.7% vs 15.4%, P < .001) findings compared with the No‐CVD group pretransplant. Post‐transplant, significant differences between groups were observed related to abnormal EKG (14.7% vs 7.0%, P = .03) and echocardiography (48.5% vs 3.2%, P < .01) findings. Pretransplant ASD spontaneously closed in 22 patients. At 1 and 5 years post‐transplant, there was no difference in the survival rate between groups (P = .96). The prevalence of CVD in recipients of LT was high, and its presence was associated with significantly higher cardiac decompensation before and after LT. Minor and moderate cardiovascular disease did not impact the long‐term survival.     

Liver abnormalities and post‐transplant survival in pediatric Fontan patients

The impact of liver parenchymal abnormalities on survival post‐heart transplant remains unknown in pediatric Fontan patients. We assessed pediatric Fontan patients who underwent heart transplant and had documented pretransplant hepatic ultrasound (U/S) studies. Liver U/S findings were classified as normal (Group 1), mildly abnormal (Group 2, hepatomegaly/vascular congestion), or severely abnormal (Group 3, heterogeneous echotexture/nodularity). Among 30 study patients, 8 were classified as Group 1, 14 as Group 2, while 8 met Group 3 criteria. Pretransplant liver biochemistry and synthetic function were similar in all groups. Six Group 3 patients underwent liver biopsy; 4 demonstrated perisinusoidal or centrilobular fibrosis, and 2 had cirrhosis. Overall mortality was 30% (n = 9). Median follow‐up was 5 years (range, 0.25‐13 years). One‐year survival was similar among all 3 groups (P = .37), with a trend toward higher cumulative 5‐year survival in Group 1 (100%). The majority of pediatric Fontan patients who underwent heart transplant demonstrated abnormal preoperative liver ultrasound findings. Heterogeneous echotexture or nodularity detected on U/S frequently indicates underlying liver parenchymal abnormalities. The presence of severe liver abnormalities was not associated with higher early mortality post‐heart transplant in pediatric Fontan patients; however, late outcomes must be further elucidated.     

Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation

Despite the improved outcomes of LT, post‐operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify the incidence of and risk factors for NCs in children who underwent LT. The medical records of pediatric patients who underwent LT at Asan Medical Center Children's Hospital between January 1994 and December 2010 were retrospectively analyzed. The onset and types of NC and pretransplant variables associated with NC were evaluated. We identified 190 children (85 boys [44.7%], 105 girls [55.3%]) of mean age 4.1 ± 4.7 yr, who underwent LT. Forty‐six NCs occurred in 41 (21.6%) patients after LT, the most common being seizures (n = 13, 28.3%) and encephalopathy (n = 10, 21.7%). Of the 46 NCs, 24 (52.2%) occurred within three months after LT. Multivariate analysis showed that primary liver disease, preoperative neurological problems, preoperatively higher serum creatinine concentration, and graft failure were significant risk factors for NCs. The survival rate was significantly lower for patients with NCs than for those without (p < 0.001). NCs after pediatric LTs were common and associated with a higher mortality rate in our study. Close monitoring and appropriate risk management may improve the long‐term outcomes of pediatric patients who undergo LT.     

Feasibility study and control values of transient elastography in healthy children

Transient elastography (TE) is a new technique for the non-invasive assessment of liver fibrosis. The degree of fibrosis is equivalent to the liver stiffness measured in kilopascal (kPa). It is frequently used in adult patients with a mean normal stiffness of 4.4–5.5 kPa. Since 2008, liver stiffness can be measured even in small children and infants following the availability of a new probe with a smaller diameter (S-probe 5 mm) than the regular probe (M-probe 7 mm). We report control values for healthy children between 0 and 18 years and investigated the feasibility of this technique in a pediatric population. For control values, TE was performed in infants and children after exclusion of liver disease by medical history, clinical examination, blood investigation, and abdominal ultrasound. For feasibility analyses the results of all TE performed in our clinic were analyzed irrespective of the underlying disease. Liver stiffness was measured with the S-probe (thorax diameter <45 cm (S1) or 45–75 cm (S2)) and the M-probe (thorax diameter >75 cm) according to the manufacturer’s recommendations. A total of 240 healthy children were analyzed to establish control values. The median liver stiffness was 4.7 kPa resulting in an upper limit of normal of 6.47 kPa. Median values of stiffness were significantly age dependent with 4.40, 4.73, and 5.1 kPa in children 0–5, 6–11, and 12–18 years (p = 0.001) while the interquartile range decreased with age (0.8, 0.7, and 0.6 kPa). The resulting upper limit of normal (median plus 1.64 times standard deviation) was 5.96, 6.65, and 6.82 kPa. Girls between 11 and 18 years showed a significantly lower median stiffness than boys of the same age (4.7 vs. 5.6 kPa; p < 0.005). Feasibility was tested in 975 consecutive liver stiffness measurements (LSM) in children 0–18 years of age. Patients with invalid LSM were significantly younger than those with valid LSM (5.8 vs. 9.7 years, p < 0.0001), showed a significantly higher stiffness (10.2 vs. 6.17, p < 0.0001), and examinations took significantly longer (202 vs. 160 s, p < 0.0001). TE is technically possible in children of all age groups. The upper limit of normal increases significantly with age. Due to movement artifacts the measurement is reliable from the age of 6 without sedation. In younger children the number of invalid measurements increases significantly. Further studies are needed to asses the value of TE in the diagnosis and follow-up of liver disease in pediatric hepatology.     

Outcomes of pediatric identical living‐donor liver and hematopoietic stem cell transplantation

Chronic IS is associated with significant morbidity in transplant recipients. Moreover, IS does not prevent chronic graft failure frequently. Allograft immune tolerance in LT can be induced by complete donor chimerism through allogenic HSCT combined with identical LDLT. This approach may exempt patients from chronic lifelong IS. However, it is unclear whether its benefits justify its risks. Here, we present three cases from our institution and analyze seven additional reports of children treated with HSCT/LDLT, all receiving HSCT due to hemato‐oncological indications. In eight of 10 cases, donor macrochimerism resulted in allograft tolerance. Nine patients survived. One patient died due to fulminant ADV infection. Further complications were GvHD (n = 3) and bone marrow failure (n = 2). In conclusion, donor‐specific allograft tolerance can be achieved by identical‐donor HSCT/LDLT. However, at present, this approach should generally be limited to selected indications due to a potentially unfavorable risk–benefit ratio. Novel toxicity‐reduced conditioning protocols for HSCT/LDLT in the absence of malignant or non‐hepatic disease may prove to be a sufficiently safe approach for inducing graft tolerance in children receiving a LDLT in the future. This concept may reduce the burden of lifelong IS.     

De novo hepatitis B virus infection after pediatric liver transplantations with hepatitis B core antibody‐positive donors: A single‐center 20‐yr experience

DNHB is common in countries with high prevalence of hepatitis B, and therefore, contracting hepatitis B after LT with HBcAb⁺ grafts is a major concern. We studied DNHB in 247 children (aged <18 yr) who underwent LT from 1994 to 2013. Sixty‐six of 247 recipients received HBcAb⁺ donor grafts. The incidence of DNHB was 5.7% (14 of 247 children) and that in HBcAb⁺ donor grafts was 19.7% (13 of 66 children). The incidence of DNHB without LAM prophylaxis was 31.3% (nine of 29 children), while that with prophylaxis was 10.8% (four of 37 children). LAM prophylaxis negatively correlated with DNHB by Cox regression analysis (p = 0.028, odds ratio = 0.258). Among 13 DNHB patients with HBcAb⁺ donor grafts, eight recovered from DNHB and four showed the emergence of LAM resistance. There was no DNHB‐related graft failure. This study showed that HBcAb⁺ donor graft was associated with development of DNHB, and use of LAM prophylaxis decreased the incidence of DNHB with HBcAb⁺ graft.     

Pulmonary complications after liver transplantation in children: risk factors and impact on early post‐operative morbidity

Liver transplantation (LT) is associated with high post‐operative morbidity, despite excellent survival rates. With this retrospective study, we report the incidence of early and late pulmonary complications (PC) after LT, identify modifiable risk factors for PC and analyzed the role of PC in post‐operative ventilation duration and hospital length of stay. In a series of 79 children (0‐16 years) with LT over a 12 years period, early (<3 months post‐LT) and/or late (>3 months post‐LT) PC occurred in 68 patients (86%). Sixty‐four percent (64%) developed early major complications such as pulmonary edema, atelectasis, or pleural effusion. Atelectasis requiring an intervention (P ≤ .02), pulmonary edema (P ≤ .02), or elevated PELD/MELD scores (P = .05) were associated with an increase in total ventilation duration and length of stay in the ICU. Risk factors for early PC included preoperative hypoxemia (P = .005), low serum albumin at LT admission (P = .003), or early rejection (P = .002). About 20% of patients experienced late PC of which 81% were infections. Risk factor assessment prior to LT may ultimately help reduce early PC thereby possibly minimizing post‐operative morbidity and ICU length of stay.     

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.     

Basiliximab treatment for steroid‐resistant rejection in pediatric patients following liver transplantation for acute liver failure

An IL‐2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno‐occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.     

Basiliximab with delayed introduction of calcineurin inhibitors as a renal‐sparing protocol following liver transplantation in children with renal impairment

Renal impairment is frequently compromised in patients with end‐stage liver disease and is associated with increased long‐term mortality post‐LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal‐sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre‐LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m² vs. 144 mL/min/1.73 m²; p = 0.56) or at 5–8 yr following LT, (129 mL/min/1.73 m² vs. 130 mL/min/1.73 m²; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal‐sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long‐term kidney function.     

Parental functioning improves the developmental quotient of pediatric liver transplant recipients

Psychomotor development in pediatric liver transplant (LT) recipients depends on several factors. Our aim was to evaluate the importance of parental involvement and family dynamics on psychomotor development by assessing (i) children and parents individually, (ii) the parent–child relationship, and (iii) the correlation between parental functioning and patient outcome, all before and after LT. Age‐appropriate scales were used before and after LT. Twenty‐one patients, 19 mothers, and 16 fathers were evaluated. Developmental quotient (DQ): No subjects scored in the “very good” range. The proportion of children with deficits increased from LT to two yr: 17.6% vs. 28.6%. Subjects 0–2 yr were more likely to have normal DQ at transplant (66.7% vs. 50% for older children). Abnormal DQ was more prevalent two yr post‐LT in children older at LT (p = 0.02). The mother–child relationship was normal in 59% of families pre‐LT and in 67% at two yr. The relationship was more favorable when the child received a transplant as an infant (p = 0.014 at 12 months post‐LT). Normal DQ was associated with higher maternal global functioning score pre‐LT (p = 0.03). Paternal performance scores were higher than maternal scores. Children transplanted after two yr of age suffer greater long‐term deficits than those transplanted as infants.     

Factors associated with immune hemolytic anemia after pediatric liver transplantation

Immune‐mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single‐center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune‐mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL‐1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV‐negative recipients who received an organ from a CMV‐positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post‐LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV‐negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL‐1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.