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.     

Physical activity and its correlates in a pediatric solid‐organ transplant population

PA has been shown to have benefits in SOT patients. Studies assessing physical activity levels and its correlates in a pediatric solid‐organ transplant population are limited. The aim of this study was to assess PA levels and identify baseline and contemporaneous factors that contribute to PA in a pediatric SOT population. A retrospective cross‐sectional review was performed on 58 pediatric transplant patients (16 heart, 29 kidney, and 13 liver transplant). PA was measured by PAQ‐C or PAQ‐A. Demographics, baseline, and contemporaneous factors were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.2 [12.3‐17.3] years old at time of completing the PAQ. Median PAQ score was 2.2 [1.7‐2.9]. There were no significant differences in PAQ scores between organ transplant type or between genders. Lower PAQ score was associated with sensory disability (9 vs 49 without disability; P = <.01) and age at time of completing the PAQ (r = ?.50, P = <.01). These results suggest that older age at time of completing the PAQ and presence of sensory disability may influence PA levels in the pediatric SOT population.     

Impact of mechanical circulatory support on survival in pediatric heart transplantation

Evidence on the impact of MCS on pediatric heart transplant survival is still scarce related to congenital heart disease patients including univentricular physiology as well as the risk factors for complications. We performed a retrospective review of all urgent pediatric (aged ≤16 years) HT from 2004 to 2014 in the Spanish Pediatric Heart Transplant Registry Group. Patients were stratified into two groups: urgent 0 (MCS at HT) and urgent 1 (non‐MCS at HT). The primary outcome measure was post‐transplant survival; secondary outcome measures were complications and absence of infections and rejection during the first post‐transplant year. One hundred twenty‐one pediatric patients underwent urgent HT, 58 (47.9%) urgent 0 and 63 (52%) urgent 1. There were 30 (24.8%) deaths: 12 in the urgent 0 group and 18 in the urgent 1 group, P = n.s. Regarding the type of MCS, patients on ECMO had the highest rate of complications (80%) and mortality (40%). Patients in the urgent 1 group showed a higher risk of hospital re‐admission for infection during the first year after transplantation (OR 2.31 [1.1‐4.82]), P = .025. We did not identify a risk factor for mortality. MCS does not impact negatively on survival after HT. However, there is a significant increase in 30‐day and 1‐year mortality and complications in ECMO patients compared with VAD patients. Infants, congenital heart disease, and PediMACS were not found to be risk factors for mortality.     

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.     

Outcomes in pediatric hepatitis C transplant recipients: Analysis of the UNOS database

HCV may lead to the development of ESLD in late childhood and, consequently, contributes to the need for liver transplantation. The aim of this study was to examine post‐transplant outcomes in HCV‐positive pediatric patients with ESLD from any cause and to determine the impact of the PELD scoring system, introduced in February 2002, on post‐transplant patient and graft survival. A retrospective analysis of the UNOS database from 1994 to 2010 was performed to assess graft and patient survival in pediatric HCV‐seropositive liver transplant recipients. Graft survival and patient survival comparing subjects in the pre‐PELD era and post‐PELD era were analyzed using Kaplan–Meier statistics. Factors associated with survival were identified using Cox regression analysis. Of 120 pediatric HCV transplant recipients, 80 were transplanted in the pre‐PELD era and 40 were transplanted post‐PELD. Median serum total bilirubin, INR, and creatinine were 4.8 mg/dL, 1.6, and 0.7 mg/dL in the pre‐PELD era vs. 5.5 mg/dL, 1.7, and 0.6 mg/mL, respectively, in the post‐PELD era (p NS). One‐yr graft survival in the pre‐PELD vs. post‐PELD era was 65.0% and 89.7%, respectively (p < 0.01); corresponding three‐yr graft survival was 57.3% vs. 76.2% (p = 0.04). One‐yr patient survival in the pre‐PELD vs. post‐PELD era was 79.0% and 97.5%, respectively (p < 0.01); corresponding three‐yr survival was 79.0% vs. 89.4% (p = 0.17). Twenty‐eight patients (23.3%) were retransplanted: 24 (30%) in the pre‐PELD era (median time to retransplant 272 days) and four (10%) in the post‐PELD era (median time to retransplant 586 days). Early follow‐up demonstrates a trend toward improved pediatric HCV liver transplant graft and patient survival in the post‐PELD era. Superior outcomes may be attributed to pretransplant factors, improved surgical technique and better treatment options for HCV infection.     

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.     

Long‐term outcomes of liver transplantation for hepatoblastoma: A single‐center 14‐year experience

HB is the most common primary liver tumor in children. Complete tumor excision, either by partial resection or by total hepatectomy and liver transplantation, in combination with chemotherapy provides the best chance for cure. We performed a retrospective analysis of patients who underwent liver transplantation for HB and herein present our 14‐year single‐institution experience. Twenty‐five patients underwent liver transplantation for HB at a median age of 26 months (IQR: 15‐44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5 years, respectively. There were four patient deaths, three of them due to disease recurrence within the first year post‐transplant. Ten‐year overall survival was 84%. Three recipients initially presented with pulmonary metastases and underwent resection of metastatic disease, of which two are alive at 3.9 years. Of three patients who underwent salvage transplants, two are alive at 1.5 years after transplant. Non‐survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21 707 vs 343 214; P = .04). In conclusion, the overall long‐term outcome of primary liver transplantation for HB is excellent. Tumor recurrence was the highest contributor to mortality. Even patients with completely treated pulmonary metastases prior to transplant demonstrated a favorable survival.     

A comprehensive strategy in donor acceptance: Impact on pediatric waitlist and heart transplant outcomes

Significant inter‐ and intra‐center practice variability is present in pediatric donor heart acceptability. This may contribute to variation in the donor refusal rate and may impact waitlist time, morbidity, mortality, and transplant rates. In order to reduce practice variability, our center developed and implemented a comprehensive strategy regarding donor acceptance in September 2017. The aim of this study was to assess the impact of this strategy on waitlist time and outcomes as well as early post‐transplant outcomes. We performed a single‐center, retrospective analysis of all pediatric (<18 years) patients listed for single‐organ heart transplant at our center from September 2015 to September 2018. Patients were divided into those listed before (Group 1) and after implementation of the comprehensive strategy (Group 2). The primary end‐point was waitlist time. Secondary end‐points included waitlist removal due to death or clinical deterioration, donor refusals per listed patient, early post‐transplant outcomes (graft failure, mechanical ventilation time, inotropic support, length of hospital stay) and 1‐year post‐transplant survival. Of 78 listed patients, 54 were transplanted (29 in Group 1), 9 were removed due to death or clinical deterioration (7 in Group 1) and 15 were removed due to clinical improvement (12 in Group 1). The waitlist time was significantly shorter in Group 2 (17 days, IQR 7‐53) vs Group 1 (90 days, IQR 14‐162); P = .006. The number of donor refusals was lower in Group 2 (1, IQR 0‐2.2) vs Group 1 (4, IQR 2‐19); P < .001. The percentage of refused donors with normal function (Left ventricular ejection fraction > 50%) was lower in Group 2 vs Group 1 (53% vs 84%; P < .001). Difference in removal from the waitlist for death or deterioration in Group 2 vs Group 1 (n = 2, 7% vs n = 7, 20%, P = .18) did not reach statistical significance. There was no difference in post‐transplant outcomes between groups. The waitlist time and donor refusals significantly decreased after implementation of a comprehensive donor acceptance strategy without impacting transplant outcomes. This analysis supports the need for a comprehensive approach to donor organ acceptance within a pediatric transplant center.     

The impact of public health service increased risk donors in pediatric liver transplantation

Many transplant programs are reluctant to use organs from deceased donors designated as “PHS increased risk” due to misconceptions regarding the quality of those organs. This study evaluated the impact of PHS increased risk donors on patient and allograft survival in pediatric patients undergoing liver transplantation. Retrospective analysis of the UNOS database from January 2005 through September 2017 revealed 5615 pediatric patients who underwent isolated liver transplantation; of these, 5057 patients received primary isolated liver transplants and 558 patients received isolated liver retransplants. PHS increased risk organs were used in 6.7% and 5.4% of the children receiving primary isolated and retransplant livers, respectively. Cox proportional hazards models adjusted for donor and recipient characteristics determined the relative risk of PHS status on allograft and patient survival. Sicker children (those in ICU [P < .001] and on life support [P = .04]) were more likely to receive PHS increased risk donor organs. There were no differences in overall patient (P = .61) or allograft (P = .68) survival between pediatric patients receiving PHS positive vs PHS negative deceased donor organs; adjusted models also demonstrated no statistically significant differences in patient or allograft survival. Excellent patient and allograft survival can be accomplished with PHS increased risk organs.     

Kidney and liver transplantation in children with fibrocystic liver–kidney disease: Data from the US Scientific Registry of Transplant Recipients: 1990–2010

The natural history and survival of children with fibrocystic liver–kidney disease undergoing solid organ transplantation have infrequently been described. We report outcomes in a cohort of US children with fibrocystic liver–kidney disease receiving solid organ transplants over 20 yr. Retrospective cohort study of pediatric transplant recipients with diagnoses of fibrocystic liver–kidney disease from 1/1990 to 3/2010, using data from the SRTR. Subjects were categorized by the first transplanted organ: LT, KT, or SLK. Primary outcomes were death, re‐transplant, transplant of the alternate organ, or initiation of dialysis. Seven hundred and sixteen subjects were transplanted in this period. Median age at first transplant was 9.7 yr. Of the LT, 14 (19%) required a second liver transplant at median of 0.2 yr, and five (7%) required kidney transplant or dialysis at a median of 9.0 yr. Of the KT, 188 (31%) required a second kidney transplant or dialysis at a median of 5.9 yr. Twenty‐nine (5%) subsequently received liver transplant at a median of 6.0 yr. Among patients in this registry, far more children underwent kidney than liver transplants. The risk of subsequently needing transplantation of an alternate organ was low.     

Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience

Arnon R, Kerkar N, Davis MK, Anand R, Yin W, González‐Peralta RP for the SPLIT Research Group. Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience.
Pediatr Transplantation 2010: 14:796–805. © 2010 John Wiley & Sons A/S. Abstract: Metabolic diseases are the second largest indication for LT in children after BA. There are limited data on the long‐term post‐transplant outcome in this unique group of patients. Therefore, our aim was to assess post‐liver transplant outcomes and to evaluate risk factors for mortality and graft loss in children with metabolic disorders in comparison to those with non‐metabolic diagnoses. We reviewed all patients enrolled in the SPLIT registry. Between 1995 and 2008, 446 of 2997 (14.9%) children enrolled in SPLIT underwent liver transplant for metabolic diseases. One‐yr and five‐yr patient survival for children with metabolic diseases was 94.6% and 88.9% and for those with other diseases 90.7% and 86.1% (log‐rank p = 0.05), respectively. One‐yr and five‐yr graft survival for children with metabolic disorders was 90.8% and 83.8%, and for those with other diseases 85.4% and 78.0% (log‐rank p = 0.005), respectively. Children with metabolic diseases were less likely to experience gastrointestinal complications (5.6% vs. 10.7%, p = 0.001), portal vein thrombosis (2.9% vs. 5.2%, p = 0.04), and reoperations within 30 days post‐transplant (33.4% vs. 37.8%, p = 0.05) than those with other indications. In conclusion, children who underwent liver transplant for metabolic disease had similarly excellent patient survival as, and better graft survival than, those who received a liver allograft for other indications.     

Hepatic pathology after Fontan palliation: spectrum of imaging findings

Background

Patients with congenital heart disease corrected by Fontan palliation have chronic liver congestion that commonly progresses to fibrosis and cirrhosis with resultant complications.

Objective

To define the hepatic imaging characteristics associated with Fontan circulation.

Materials and methods

A retrospective study was performed in patients who underwent Fontan palliation who had CT or MR examinations including the liver. The liver was evaluated for parenchymal morphology, abnormal enhancement, nodules and imaging findings of fibrosis and cirrhosis.

Results

MRI or CT examinations including the liver were evaluated in 42 Fontan patients. The most common imaging finding was abnormal parenchymal enhancement, present in 38 patients. Hypervascular nodules were present in 13 patients (31%). Imaging findings of cirrhosis were seen in eight patients (19%). One patient with cirrhosis had a large liver mass, subsequently diagnosed as fibrolamellar hepatocellular carcinoma.

Conclusion

A high percentage of patients had imaging abnormalities of the liver, chiefly abnormal parenchymal enhancement, which became more apparent as the duration of the Fontan circulation increased. The hypervascular nodules sometimes present had imaging characteristics most closely resembling those of focal nodular hyperplasia. The underlying fibrosis and eventual development of cirrhosis raise the risk of developing hepatocellular carcinoma.     

Surgical treatment of primary liver tumors in children: Outcomes analysis of resection and transplantation in the SEER database

Adjusted survival outcomes following hepatic resection and transplantation for pediatric liver tumors have not been compared. To address this question, we conducted a retrospective cohort study using the SEER registry. While SEER lacks certain specifics regarding staging, chemotherapy, comorbidities, and recurrence, important hypothesis‐generating data are available and were analyzed using Kaplan–Meier statistics and Cox proportional hazards regression. All SEER patients under the age of 20 yr undergoing surgery for HB (n = 318) or HCC (n = 80) between 1998 and 2009 were included. Of HB patients, 83.3% underwent resection and 16.7% transplantation. Advanced disease, vascular invasion, and satellite lesions were more common among transplant patients. Unadjusted five‐yr survival was equivalent, as was the adjusted hazard of death for transplant relative to resection (HR = 0.58, p = 0.63). Of HCC patients, 75.0% underwent resection and 25.0% transplantation. Transplant patients had a higher prevalence of vascular invasion and satellite lesions. Five‐yr survival was 53.4% after resection and 85.3% after transplant, and the adjusted hazard of death was significantly lower after transplantation (HR = 0.05, p = 0.045). While transplantation is generally reserved for unresectable tumors, the favorable survival seen in HCC patients suggests that liberalized transplant criteria might improve survival, although further prospective data are needed.     

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re‐transplantation. TE is a non‐invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05‐1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.     

Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients

CAV remains a leading cause of late graft loss and mortality among survivors of pediatric heart transplantation. We sought to define the incidence of CAV and identify its predictors in pediatric heart transplant recipients. The OPTN/UNOS database was analyzed for pediatric recipients who underwent heart transplant between 1987 and 2011. The primary end‐point is time from heart transplantation to development of CAV (CAV‐free survival). To identify predictors of CAV‐free survival, demographic and transplant data were analyzed by the Kaplan–Meier survival method and Cox proportional hazards regression. Of 5211 pediatric heart transplant recipients with at least one‐yr follow‐up, the incidence of CAV at five, 10, and 15 yr was 13%, 25%, and 54%, respectively. Multivariate analysis found that risk of CAV was associated with the following variables: Recipient age 1–4 yr (HR 1.25), 5–9 yr (1.45), 10–18 yr (1.83), donor age >18 yr (1.34), re‐transplantation (2.14), recipient black race (1.55), and donor cigarette use (1.54). Older recipient and donor age, recipient black race, donor cigarette use, and re‐transplantation were highly associated with shorter CAV‐free survival.     

Donor‐to‐recipient weight ratio is a risk factor for hepatic artery thrombosis after whole‐liver transplantation in children under 25 kg

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased‐donor liver transplantation from August 2002 to July 2016. Multi‐organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased‐donor liver transplant patients with a median age of 1.7 years (IQR 0.67‐6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole‐liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split‐liver graft recipients. Within the whole‐liver recipient group under 25 kg, 11 patients developed HAT with a median donor‐to‐recipient ratio (DRWR) of 0.9 (IQR: 0.7‐1.2) compared with a median DRWR of 1.4 (IQR: 1.1‐1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split‐liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.     

Reducing the incidence of hepatic artery thrombosis in pediatric liver transplantation: Effect of microvascular techniques and a customized anticoagulation protocol

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986‐2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008‐2012, microvascular techniques were introduced. In E3, 2012‐2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post‐liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.     

Impact of donor preprocurement cardiac arrest on clinical outcomes in pediatric deceased donor liver transplantation

PPCA has historically been considered detrimental to donor quality in LT, but transplantation of grafts from this group of donors is now routine. Our study aims to evaluate the outcomes associated with use of donors with a history of PPCA in the pediatric population. This study is a single‐center retrospective analysis of all pediatric LTs performed over an 18‐year period. Donors and recipients were stratified by the presence and length of donor PPCA time. Preprocurement donor and post‐transplant recipient laboratory values were collected to assess the degree of ischemic liver injury associated with each donor group. Cox regression analysis was used to compare survival. The records for 130 deceased pediatric LT donors and corresponding recipients were reviewed. There were 73 (56%) non‐PPCA donors and 57 (44%) PPCA donors. Donors that experienced a PPCA event demonstrated a higher median, pretransplant peak alanine aminotransferase (ALT) level (P < .001). When comparing post‐transplant recipient median ALT levels, donors with any PPCA had lower median peak ALT (P = .15) and day 3 ALT (P = .43) levels than the non‐PPCA group. Rates of early graft loss did not differ. The PPCA group with >40 minutes of ischemia had markedly lower survival at 10 years, but this finding did not reach statistical significance. Liver grafts from donors with or without PPCA demonstrated no statistically significant differences in function or survival. A history of donor PPCA alone should not be used as an exclusionary criterion in pediatric liver transplantation.     

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.     

Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus to prolonged‐release tacrolimus formulation

This study was a Phase II, open‐label, multicenter, single‐arm, cross‐over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate‐release tacrolimus (IR‐T) to prolonged‐release tacrolimus (PR‐T). In Days ?30 to ?1 of screening period, patients received their IR‐T‐based regimen; during Days 1‐7, patients received study IR‐T (same dose as screening). On Day 7, the first 24‐hours PK profile was taken; patients were then converted to PR‐T (1 mg:1 mg), with a second 24‐hours PK profile taken on Day 14. The primary end‐point was tacrolimus area under the blood concentration–time curve over 24 hours (AUC₂₄); secondary end‐points were maximum concentration C_maxand concentration at 24 hours C₂₄. The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%‐125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR‐T:IR‐T LSM ratio (90% CI) was similar overall for AUC₂₄, _max, and C₂₄, and for kidney and liver recipients for AUC₂₄ (LSM ratio, kidney 91.8%; liver 104.1%) and C₂₄ (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC₂₄ and C₂₄, and between PR‐T and IR‐T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR‐T to PR‐T at the same total daily dose, using the same therapeutic drug monitoring method.