Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort.

BACKGROUND AND AIMS: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. APPROACH AND RESULTS: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. CONCLUSIONS: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.

Association of state Medicaid expansion policies with pediatric liver transplant outcomes.

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P < .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P < .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation.

Pushing the Limits of In Situ Split Liver Procurement to Overcome Donor Distance and Graft Size Challenges for 8-Week-Old Pediatric Recipient.

BACKGROUND: Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient. CASE PRESENTATION: An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions. CONCLUSIONS: In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes.

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.

BACKGROUND: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.

An ethical analysis of obesity as a contraindication to pediatric liver transplant candidacy.

Childhood obesity is becoming more prevalent in the United States (US) and worldwide, including among children in need of a liver transplant. Unlike with heart and kidney failure, end-stage liver disease (ESLD) is unique in that no widely available medical technology can re-create the life-sustaining function of a failing liver. Therefore, delaying a life-saving liver transplant for weight loss, for example, is much harder, if not impossible for many pediatric patients, especially those with acute liver failure. For adults in the United States, guidelines consider obesity a contraindication to liver transplant. Although formal guidelines are lacking in children, many pediatric transplant centers also consider obesity a contraindication to a pediatric liver transplant. Variations in practice among pediatric institutions may result in biased and ad hoc decisions that worsen healthcare inequities. In this article, we define and report the prevalence of childhood obesity among children with ESLD, review existing guidelines for liver transplant in adults with obesity, examine pediatric liver transplant outcomes, and discuss the ethical considerations of using obesity as a contraindication to pediatric liver transplant informed by the principles of utility, justice, and respect for persons.

Allocation to pediatric recipients around the world: An IPTA global survey of current pediatric solid organ transplantation deceased donation allocation practices.

BACKGROUND: There has not been a comprehensive global survey of pediatric-deceased donor allocation practices across all organs since the advent of deceased donor transplantation at the end of the 20th century. As an international community that is responsible for transplanting children, we set out to survey the existing landscape of allocation. We aimed to summarize current practices and provide a snapshot overview of deceased donor allocation practices to children across the world. METHODS: The International Registry in Organ Donation and Transplantation (IRODAT, www.irodat.org) was utilized to generate a list of all countries in the world, divided by continent, that performed transplantation. We reviewed the published literature, published allocation policy, individual website references and associated links to publicly available listed allocation policies. Following this, we utilized tools of communication, relationships, and international fellowship to confirm deceased donation pediatric centers and survey pediatric allocation practices for liver, kidney, heart, and lung across the world. We summarize pediatric allocation practices by organ when available using source documents, and personal communication when no source documents were available. RESULTS: The majority of countries had either formal or informal policies directed toward minimizing organ distribution disparity among pediatric patients. CONCLUSION: Children have long-term life to gain from organ donation yet continue to die while awaiting transplantation. We summarize global strategies that have been employed to provide meaningful and sustained benefit to children on the waitlist.

Liver simulated allocation model does not effectively predict organ offer decisions for pediatric liver transplant candidates.

The SRTR maintains the liver-simulated allocation model (LSAM), a tool for estimating the impact of changes to liver allocation policy. Integral to LSAM is a model that predicts the decision to accept or decline a liver for transplant. LSAM implicitly assumes these decisions are made identically for adult and pediatric liver transplant (LT) candidates, which has not been previously validated. We applied LSAM's decision-making models to SRTR offer data from 2013 to 2016 to determine its efficacy for adult (≥18) and pediatric (<18) LT candidates, and pediatric subpopulations-teenagers (≥12 to <18), children (≥2 to <12), and infants (<2)-using the area under the receiver operating characteristic (ROC) curve (AUC). For nonstatus 1A candidates, all pediatric subgroups had higher rates of offer acceptance than adults. For non-1A candidates, LSAM's model performed substantially worse for pediatric candidates than adults (AUC 0.815 vs. 0.922); model performance decreased with age (AUC 0.898, 0.806, 0.783 for teenagers, children, and infants, respectively). For status 1A candidates, LSAM also performed worse for pediatric than adult candidates (AUC 0.711 vs. 0.779), especially for infants (AUC 0.618). To ensure pediatric candidates are not unpredictably or negatively impacted by allocation policy changes, we must explicitly account for pediatric-specific decision making in LSAM.

The current state of pediatric transplant hepatology fellowships: A survey of recent graduates.

BACKGROUND: The number of programs offering a PTH fellowship has grown rapidly over the last 10 years. This study aimed to describe the clinical, didactic, procedural, and research experiences of recent PTH fellowship graduates. In addition, we sought to understand graduates' post-fellowship professional responsibilities and their perception about the utility of the PTH fellowship. METHODS: An anonymous survey was distributed from February to October 2020 through REDCap to all recent graduates (2015-2019) of an ACGME-approved PTH fellowship program. The survey consisted of 49 questions focused on the PTH fellowship experience. Results were summarized using descriptive statistics. RESULTS: Thirty-eight of 43 graduates (88%) responded to the survey representing 12 PTH fellowship programs. The didactic experience varied; 97% received pathology lectures, 81% radiology lectures, 54% organ allocation lectures, 54% procedural lectures, 57% immunology lectures, and 43% live donation lectures. During the PTH fellowship, the majority of fellows performed >10 liver biopsies (82%) and >5 variceal bandings (58%); however, 63%, 32%, 8%, and 8% never performed paracentesis, variceal sclerotherapy, variceal banding, and liver biopsies, respectively. The majority of fellows (95%) completed a research project during PTH fellowship. Currently, 84% of graduates are employed at a transplant academic institution. All graduates recommended the fellowship. CONCLUSIONS: There is variability in the didactic, clinical, and procedural training among PTH fellowship programs. Although uniformly viewed as a beneficial fellowship year, there is an opportunity to collaborate to create a more standardized training experience.

A Learning Health System for Pediatric Liver Transplant: The Starzl Network for Excellence in Pediatric Transplantation.

OBJECTIVE: Learning health systems (LHS) integrate research, improvement, management, and patient care, such that every child receives "the right care at the right time...every time," that is, evidence-based, personalized medicine. Here, we report our efforts to establish a sustainable, productive, multicenter LHS focused on pediatric liver transplantation. METHODS: The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) is the first multicenter effort by pediatric liver transplant families and providers to develop shared priorities and a shared agenda for innovation in clinical care. This report outlines SNEPT's structure, accomplishments, and challenges as an LHS. RESULTS: We prioritized 4 initial projects: immunosuppression, perioperative anticoagulation, quality of life, and transition of care. We shared center protocols/management to identify areas of practice variability between centers. We prioritized actionable items that address barriers to providing "the right care at the right time" to every pediatric liver transplant recipient: facilitating transparency of practice variation and the connection of practices to patient outcomes, harnessing existing datasets to reduce the burden of tracking outcomes, incorporating patient-reported outcomes into outcome metrics, and accelerating the implementation of knowledge into clinical practice. This has allowed us to strengthen collaborative relationships, design quality improvement projects, and collect pilot data for each of our priority projects. CONCLUSIONS: The field of pediatric liver transplantation can be advanced through application of LHS principles. Going forward, SNEPT will continue to unite patient advocacy, big data, technology, and transplant thought leaders to deliver the best care, while developing new, scalable solutions to pediatric transplantation's most challenging problems.

Transjugular intrahepatic portosystemic shunt creation may be associated with hyperplastic hepatic nodular lesions in the long term: an analysis of 18 pediatric and young adult patients.

BACKGROUND: Retrospective studies have demonstrated the efficacy and safety of pediatric and adolescent transjugular intrahepatic portosystemic shunt (TIPS), but long-term outcomes warrant further investigation. OBJECTIVE: To report on the development of hyperplastic hepatic nodular lesion development in children and young adults (<21 years) with TIPS patency >3 years. MATERIALS AND METHODS: Eighteen children and young adults, including 10 (55.6%) females and 8 (44.4%) males, underwent TIPS creation with >3 years' patency and follow-up evaluation at a tertiary children's hospital. The mean age at the time of TIPS creation was 12.5±5.1 years (range: 1.5-20.0 years). The mean model for end-stage liver disease (MELD) at the time of TIPS creation was 8.1±1.6 (range: 6-11). Indications for TIPS creation included acute variceal bleeding (8/18, 44.4%), primary (1/18, 5.6%) or secondary (7/18, 38.9%) prevention of varices, portal vein thrombosis (1/18, 5.6%), and splenic sequestration (1/18, 5.6%). Technical successes, intra-procedural parameters, hemodynamic and clinical successes, TIPS patencies, adverse events, imaging evaluations, and follow-ups were recorded. RESULTS: All (100%) TIPS placements were successful; however, a direct intrahepatic portosystemic shunt was created in one (5.6%) patient. Mean reduction of the portosystemic shunt gradient was 9.1±3.3 mmHg (range: 4-16 mmHg). Seventeen (94.4%) patients demonstrated clinical success with resolution of their initial clinical indication for TIPS placement. The 3-year TIPS primary, primary-assisted, and secondary patencies were 83.3% (15/18), 94.4% (17/18), and 100% (18/18), respectively. Two (11.1%) patients developed mild, medically controlled hepatic encephalopathy. One (5.6%) patient developed hepatopulmonary syndrome. Nine (50%) patients developed single or multiple hepatic nodules at a mean imaging surveillance time after TIPS of 4.4±3.0 years (range: 1.5-10.2 years). Six (33.3%) patients developed nodules >1 cm with imaging features most consistent with focal nodular hyperplasia or focal nodular hyperplasia-like nodules. The mean follow-up duration was 5.7±2.9 years (range: 3.0-13.1 years). CONCLUSION: Long-term (>3 years) portosystemic shunting via TIPS is associated with the development of hepatic nodular lesions in children. Consequently, children with TIPS may need gray-scale assessment of hepatic parenchyma as part of routine ultrasound exams and extended imaging surveillance until more is understood regarding the natural history of induced nodularity.

Split liver transplantation is utilized infrequently and concentrated at few transplant centers in the United States.

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as "primary" and "secondary" transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing "optimal" split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety-two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty-seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94-1.00, P = .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults.

Livers From Pediatric Donation After Circulatory Death Donors Represent a Viable and Underutilized Source of Allograft.

Despite increased numbers of donation after circulatory death (DCD) donors, pediatric DCD livers are underused. To investigate possible reasons for this discrepancy, we conducted a retrospective cohort study using 2 data sets from the Organ Procurement and Transplantation Network for all deceased liver donors and for all recipients of DCD liver transplants from March 8, 1993, to June 30, 2018. Pediatric (0-12 years) and adolescent (13-17 years) DCD donors were compared with those aged 18-40 years. We found that pediatric DCD allografts are recovered at a significantly lower rate than from 18-to-40-year-old donors (27.3% versus 56.3%; P < 0.001). However, once recovered, these organs are transplanted at a similar rate to those from the 18-to-40-year-old donor cohort (74.7% versus 74.2%). Significantly more pediatric DCD livers (odds ratio [OR], 3.75; confidence interval [CI], 3.14-4.47) were not recovered compared with adult organs, which were most commonly not recovered due to organ quality (10.2% versus 7.1%; P < 0.001). The 10-year relative risks (RRs) for graft failure and patient death were similar between pediatric and adult DCD donors, with adolescent DCD livers demonstrating improved outcomes. DCD livers transplanted into pediatric donors were protective against graft failure (RR, 0.46; 95% confidence interval [CI], 0.21-0.99) and patient death (RR, 0.16; 95% CI, 0.04-0.69). In conclusion, despite lower rates of recovery, pediatric DCD livers represent a viable organ source for certain adults and children.

Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience.

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

Deceased Pediatric Donor Livers: How Current Policy Drives Allocation and Transplantation.

Each year, approximately 60 children, representing 12% of waitlist candidates, die awaiting liver transplantation. The current allocation algorithm for pediatric donor livers prioritizes local/regional adults over national children. We attempted to better understand the impact of the present algorithm on pediatric candidates. We analyzed pediatric donor liver offers from 2010 to 2014. Donors and recipients were classified based on age. We mapped allocation and acceptance patterns and used subgroup analyses to explore the significance of donor service areas (DSAs) with low pediatric transplant volumes. We used Cox proportional hazard regressions to evaluate posttransplantation outcomes: 3,318 pediatric donor livers were transplanted into 3,482 recipients, and 45% (1,569) were adults. Of the 1,569 adults, 25% (390) received a pediatric organ that was never offered to children; 52% (204) of these 390 pediatric organs originated in the 37 DSAs, with ≤25 pediatric liver transplantations; 278 children died or were delisted due to illness during the same time, with higher mortality rates in the 37 DSAs (10% versus 6%, P < 0.01). Compared to adults, pediatric recipients aged <12 years had lower risks of posttransplant mortality (hazard ratio, 0.62; 95% confidence interval, 0.46-0.81; P < 0.01). Conclusions: We found that 45% of pediatric donor livers were transplanted into adults: 390 adults were transplanted with pediatric organs never offered to children, while 278 children died or were delisted due to illness, which was more apparent in DSAs with low pediatric transplant volumes; we advocate for a change to allocation policies to allow pediatric organs to be offered to national children with status 1B or Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease >15 before being offered to local/regional + circle non-status 1A adults.

Adults transplanted as children as retransplant candidates: Analysis of outcomes support optimism in a population mislabeled as high risk.

Adult liver transplant programs have heretofore been hesitant to perform liver retransplantation in adult patients who underwent primary liver transplantation as a child (P_A). Areas of concern include: (a) potential disruption in care when transferring from a pediatric to an adult transplant center; (b) generally inferior outcomes of retransplantation; (c) reputation of young adults for non-adherence to post-transplant regimen; and (d) potential higher work effort for equivalent outcomes. To examine these concerns, we reviewed data on all US liver adult retransplants from 10/01/1987 to 9/30/2017. We propensity matched the P_A patients to patients who received both primary and retransplantation as adults (A_A), with ≥550 days between transplants. A mixed Cox proportional hazards model with program size and time period of transplantation as random variables revealed that retransplantation of P_A patients produced no significantly different graft survival or patient survival rates than retransplantation of the matched A_A patients. Therefore, inferior rates of liver retransplantation in these patients and concerns about continuity of care in changing transplant programs are not as believed in the wider liver transplant community. In conclusion, liver transplant centers should be optimistic about retransplanting adults who received their primary transplants as children.

Hepatopulmonary Syndrome in an Adolescent With Insidious Hypoxia and Small Intrahepatic Portal Venous Shunts: Posttransplant Benefit From Sildenafil.

We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

BACKGROUND: Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. OBJECTIVE: To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. MATERIALS AND METHODS: Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. RESULTS: Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0-15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1-15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0-15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5-15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0-8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2-9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12-20 mmHg) (P=0.006). CONCLUSION: HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Pressure gradients, laboratory changes, and outcomes with transjugular intrahepatic portosystemic shunts in pediatric portal hypertension.

INTRODUCTION: Indications for TIPS are well described in adults and involve complications of PHTN. Complications from PHTN are associated with PSG of > 12 mm Hg in adults. It is unclear if these parameters apply to children with PHTN. OBJECTIVE: To assess whether adult criteria for TIPS placement can be utilized in children, describe laboratory changes over time, and report outcomes. METHODS: We performed a retrospective review of 34 pediatric patients who underwent TIPS, examining indications, radiology, PSG reductions, laboratory changes, and outcomes. RESULTS: Most patients had PHTN due to parenchymal liver disease including congenital hepatic fibrosis (n = 5), biliary atresia (n = 5), cystic fibrosis-related liver disease (n = 3) and cavernous transformation of the portal vein (n = 6). Indications for TIPS included variceal bleeding, recurrent ascites, and maintenance of portal vein flow following thrombolysis. Variceal bleeding was observed in six children with PSG < 12 mm Hg. Minor complications occurred in eight subjects. Continued bleeding occurred in one patient. Six patients were successfully bridged to transplantation, and three patients died secondary to end-stage disease. Standard laboratory tests stabilized after TIPS placement and hematocrit increased. CONCLUSION: TIPS placement in pediatric patients was performed for complications of PHTN. Unlike adult series, a substantial proportion of our cases treated extrahepatic PHTN from cavernous transformation of the portal vein. Children presented with sequelae of PHTN with PSG below 12 mm Hg, below the adult standard. We found TIPS in pediatrics to be safe and effective with laboratory stabilization and improvement in hematocrit.

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.