RESUMO
BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
Assuntos
Síndrome de Alagille , Humanos , Síndrome de Alagille/complicações , Síndrome de Alagille/tratamento farmacológico , Feminino , Masculino , Estudos Retrospectivos , Criança , Lactente , Pré-Escolar , Intervalo Livre de Progressão , Adolescente , Proteínas de Transporte , Glicoproteínas de MembranaRESUMO
Pediatric liver transplant (LT) recipients navigate a lifelong journey that includes constant monitoring and challenges. Research priorities and questions in LT have traditionally been provider-driven. This project was a novel partnership between a learning health system dedicated to pediatric LT (Starzl Network for Excellence in Pediatric Transplantation) and a parent-led advocacy group (Transplant Families) that aimed to prepare families and providers for collaborative patient-centered outcomes research (PCOR). We developed 5 virtual modules to (1) teach participants about PCOR, and (2) elicit ideas for PCOR priorities and processes in pediatric LT. Parents and providers participated via self-guided online modules or focus groups. Participants included 240 patient partners and 133 pediatric LT providers from 16 centers over 2 years. We held 20 focus groups, including 5 to amplify underrepresented voices: young adults, Spanish speakers, and African Americans. Feedback was summarized to create a PCOR Roadmap, a guide for future PCOR in the Starzl Network, which was disseminated back to participants online and via webinars. Feedback from a diverse group of stakeholders allowed us to develop PCOR priorities and processes for the pediatric LT community. Our engagement strategies could be adapted by other transplant communities to facilitate patient and provider research partnerships.
Assuntos
Assistência Centrada no Paciente , Humanos , Criança , Masculino , Feminino , Transplantados , Transplante de Fígado , Adulto , Grupos Focais , Avaliação de Resultados da Assistência ao Paciente , Família , AdolescenteRESUMO
Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.
Assuntos
Cuidadores , Transplante de Fígado , Pesquisa Qualitativa , Humanos , Transplante de Fígado/psicologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/economia , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Cuidadores/economia , Masculino , Feminino , Criança , Pré-Escolar , Adulto , Adolescente , Apoio Social , Lactente , Efeitos Psicossociais da Doença , Entrevistas como Assunto , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/organização & administração , Adulto JovemRESUMO
BACKGROUND AND AIMS: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001). CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.
Assuntos
Síndrome de Alagille , Colestase , Hipertensão Portal , Humanos , Criança , Masculino , Feminino , Síndrome de Alagille/epidemiologia , Estudos Retrospectivos , Hipertensão Portal/etiologiaRESUMO
OBJECTIVES: To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction. METHODS: Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation. RESULTS: We constructed a prognostic joint model that combines the temporal trajectories of international normalized ratio, total bilirubin, hepatic encephalopathy, platelet count, and serum creatinine. Dynamic prediction using updated information improved predictive performance over static prediction using the information at enrollment (Day 0) only. In cross-validation, AUC increased from 0.784 to 0.887 when measurements obtained between Days 1 and 2 were incorporated. AUC remained similar when we used the earlier subset of the sample for training and the later subset for testing. CONCLUSIONS: Serial measurements of five variables in the first few days of PALF capture the dynamic clinical course of the disease and improve risk prediction for mortality. Continuous disease monitoring and updating risk prognosis are beneficial for timely and judicious medical decisions.
Assuntos
Encefalopatia Hepática , Falência Hepática Aguda , Criança , Humanos , Falência Hepática Aguda/diagnóstico , Prognóstico , Bilirrubina , Progressão da DoençaRESUMO
OBJECTIVES: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes. METHODS: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries. RESULTS: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only. CONCLUSIONS: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices.
Assuntos
Transplante de Rim , Transplante de Fígado , Criança , Humanos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêuticoRESUMO
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.
Assuntos
Transtornos Linfoproliferativos , Transplante de Órgãos , Complicações Pós-Operatórias , Rituximab , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Criança , Adolescente , Rituximab/uso terapêutico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Imunossupressores/uso terapêutico , Pré-EscolarRESUMO
PURPOSE OF REVIEW: Advances in pediatric transplant parallel those in adult populations; however, there remain critical unique considerations and differences that require specialized knowledge and a specific skill set to optimize care afforded to the pediatric transplant candidate. We introduce general themes regarding optimization of the transplant candidate that are unique to children. RECENT FINDINGS: The pathologies leading to pediatric organ transplant candidacy differ from adults and a precise understanding of the physiologies and natural histories of such diseases is critical for optimized care. Regardless of etiology, comorbidities including malnutrition, sarcopenia, and developmental delay are seen and often require disease and organ specific approaches to management. Additionally, an understanding of the concepts of developmental immunology and their relevance to transplant is critical. SUMMARY: When looking to optimize pretransplant care, awareness of the pediatric-specific challenges by the transplant community in addition to organ- and age-specific management strategies enable the best outcomes for children awaiting solid organ transplantation.
Assuntos
Transplante de Órgãos , Adulto , Criança , Humanos , Transplante de Órgãos/efeitos adversos , Listas de EsperaRESUMO
To assess the impact of technical variant grafts (TVGs) [including living donor (LD) and deceased donor split/partial grafts] on waitlist (WL) and transplant outcomes for pediatric liver transplant (LT) candidates, we performed a retrospective analysis of Organ Procurement and Transplantation Network (OPTN) data on first-time LT or liver-kidney pediatric candidates listed at centers that performed >10 LTs during the study period, 2004-2020. Center variance was plotted for LT volume, TVG usage, and survival. A composite center metric of TVG usage and WL mortality was developed to demonstrate the existing variation and potential for improvement. Sixty-four centers performed 7842 LTs; 657 children died on the WL. Proportions of WL mortality by center ranged from 0% to 31% and those of TVG usage from 0% to 76%. Higher TVG usage, from deceased donor or LD, independently or in combination, significantly correlated with lower WL mortality. In multivariable analyses, death from listing was significantly lower with increased center TVG usage (HR = 0.611, CI: 0.40-0.92) and LT volume (HR = 0.995, CI: 0.99-1.0). Recipients of LD transplants (HR = 0.637, CI: 0.51-0.79) had significantly increased survival from transplant compared with other graft types, and recipients of deceased donor TVGs (HR = 1.066, CI: 0.93-1.22) had statistically similar outcomes compared with whole graft recipients. Increased TVG utilization may decrease WL mortality in the US. Hence, policy and training to increase TVG usage, availability, and expertise are critical.
Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Criança , Humanos , Estados Unidos/epidemiologia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fígado , Doadores Vivos , Sobrevivência de EnxertoRESUMO
BACKGROUND: For children with liver transplants (LT), achieving an "ideal outcome" is a balancing act: too little immunosuppression begets graft injury; too much begets systemic complications. We aimed to delineate the parental perspective on this tightrope. METHODS: Parents of children with LT completed an internet-based survey about their child's immunosuppression. RESULTS: Children of respondents (n = 82) were a median 4 years from primary LT (range 0-22); 73% were on immunosuppression monotherapy. Parents' top concerns were related to immunosuppression complications; 46% were more concerned about immunosuppression complications than rejection; only 17% were more concerned about rejection than immunosuppression complications. Among parents of children on immunosuppression monotherapy, 29% still worried more about immunosuppression complications than rejection, 48% expressed equal concern for both. Time since LT (0-4 vs. >4 years) was not associated with concern level for rejection or immunosuppression complications. Caregivers were significantly more certain that their child's immunosuppression regimen was correct to prevent rejection than to mitigate complications (p < .005). CONCLUSION: Caregivers of children with LTs reported higher levels of concern and uncertainty about immunosuppression complications than rejection risk. Understanding parent and patient perspectives on IS, and incorporating them into immunosuppression counseling and decision-making, is critical to achieving truly "ideal" long-term outcomes.
Assuntos
Transplante de Fígado , Criança , Humanos , Transplante de Fígado/efeitos adversos , Terapia de Imunossupressão , Pais/psicologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Inquéritos e QuestionáriosRESUMO
The liver is the primary organ for the metabolism of many chemotherapeutic agents. Treatment-induced liver injury is common in children undergoing cancer therapy. Hepatic injury occurs due to various mechanisms, including biochemical cytotoxicity, hepatic vascular injury, radiation-induced cytotoxicity, and direct hepatic injury through minimally invasive and invasive surgical treatments. Treatment-induced liver injury can be seen contemporaneous with therapy and months to years after therapy is complete. Patients can develop a combination of hepatic injuries manifesting during and after treatment. Acute toxic effects of cancer therapy in children include hepatitis, steatosis, steatohepatitis, cholestasis, hemosiderosis, and vascular injury. Longer-term effects of cancer therapy include hepatic fibrosis, chronic liver failure, and development of focal liver lesions. Quantitative imaging techniques can provide useful metrics for disease diagnosis and monitoring, especially in treatment-related diffuse liver injury such as hepatic steatosis and steatohepatitis, hepatic iron deposition, and hepatic fibrosis. Focal liver lesions, including those developing as a result of treatment-related vascular injury such as focal nodular hyperplasia-like lesions and hepatic perfusion anomalies, as well as hepatic infections occurring as a consequence of immune suppression, can be anxiety provoking and confused with recurrent malignancy or hepatic metastases, although there often are imaging features that help elucidate the correct diagnosis. Radiologic evaluation, in conjunction with clinical and biochemical screening, is integral to diagnosing and monitoring hepatic complications of cancer therapy in pediatric patients during therapy and after therapy completion for long-term surveillance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material See the invited commentary by Ferraciolli and Gee in this issue.
Assuntos
Carcinoma Hepatocelular , Doença Hepática Crônica Induzida por Substâncias e Drogas , Fígado Gorduroso , Neoplasias Hepáticas , Lesões do Sistema Vascular , Humanos , Criança , Neoplasias Hepáticas/diagnóstico por imagem , Recidiva Local de Neoplasia , Cirrose HepáticaRESUMO
OBJECTIVES: The objectives of this study was to describe variation in induction regimen, identify predictors of induction immunosuppression (IS) choice, and examine the impact of induction IS regimen on length of stay (LOS) and total perioperative costs in pediatric liver transplant recipients. METHODS: We analyzed liver transplant utilization data in the Pediatric Health Information System database. Patients were divided into 3 induction IS groups: (1) steroids only, (2) T-cell depleting antibody (TDA), and (3) non-TDA. We identified predictors of induction IS regimen and examined associations between each outcome and choice of induction IS. RESULTS: We analyzed 4905 liver transplant recipients (50% female, 80% under age 13 years, 42% non-Hispanic White). Most patients (3162, 64%) received steroids only induction, and about twice as many patients received a non-TDA regimen (1093, 22%) versus a TDA regimen (650, 13%). Median total perioperative costs were highest for the TDA group [$146,438 (interquartile range $113,461-$195,575)] versus the non-TDA group [$129,307 ($102,632-$173,953)] and the steroids only group ($127,049 ($98,814-$181,053)]. Compared to steroids only induction, TDA was associated with increased LOS (+2 days, P = 0.017) with no difference in cost. Non-TDA induction was associated with a decreased LOS (-3 days, P < 0.001) and increased cost (+$42,542; P < 0.001) independent of LOS. CONCLUSIONS: Compared to a steroids only induction IS regimen, non-TDA induction was associated with increased total perioperative costs, even after adjustments for LOS. Future work will combine cost and outcome data to provide decision-making support in pediatric liver transplant recipients.
Assuntos
Imunossupressores , Transplante de Fígado , Humanos , Feminino , Criança , Adolescente , Masculino , Imunossupressores/uso terapêutico , Rejeição de Enxerto , Terapia de Imunossupressão , Soro Antilinfocitário , Esteroides , TransplantadosRESUMO
Previous single-center, cross-sectional studies have reported a steep increase in the prevalence and severity of fibrosis through 10 to 15 years after pediatric liver transplantation. We report a multicenter study of paired surveillance biopsies in a contemporary cohort. Children who underwent liver transplant when younger than 6 years old and had paired surveillance liver biopsies were enrolled (n = 78, 35% girls, median 1.2 years old at transplant). A central pathologist graded inflammation, assessed rejection activity index, and staged fibrosis in the portal, sinusoidal, and perivenular compartments, allowing for calculation of the Liver Allograft Fibrosis Score (LAFSc). Analysis of variance tested associations between fibrosis progression and clinical parameters. The first biopsy, at a median 8.2 years (interquartile range, 5.9-11.6 years) after transplantation, showed absent to mild fibrosis (LAFSc 0-2) in 29%, moderate (LAFSc 3-5) in 56%, and severe (LAFSc 6-7) in 14% of patients. The second biopsy, at a median 4.7 years (IQR, 4.3-5.1 years) later, showed fibrosis progression (LAFSc increased by ≥3) in 10 (13%) and regression (LAFSc decreased by ≥3) in 4 (5%) patients. After adjusting for baseline LAFSc, younger age at transplant was the only risk factor for fibrosis progression. Although fibrosis prevalence and severity 6 to 12 years after transplant was similar to previous reports, fibrosis trajectory during the next 4 to 5 years was stable. Our data may be reassuring for children with consistently normal liver tests. A comprehensive understanding of factors determining allograft health during the very long term is essential to optimizing allograft and patient health.
Assuntos
Transplante de Fígado , Biópsia , Criança , Estudos Transversais , Feminino , Fibrose , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Lactente , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Transplante de Fígado/efeitos adversos , MasculinoRESUMO
With advances in surgical techniques, medical management, and more equitable allocation systems, children who receive a liver transplantation (LT) today can expect remarkable outcomes early after LT. However, beyond 1 year after transplant, attrition rates have not improved. We reviewed two separate eras (Era 1: January 1995-June 2004 vs. Era 2: July 2004-March 2018) of the Society of Pediatric Liver Transplantation registry to explore the evolution and associated factors contributing to late graft loss (LGL) and late mortality (LM). The fraction of long-term pediatric LT recipients surviving after 1 year with their first graft significantly improved (81.5% in Era 1 vs. 85.7% in Era 2; p < 0.0001). This improvement occurred despite significant changes in patient selection toward higher risk populations (p < 0.001) and without notable improvement in perioperative complications such as hepatic artery thrombosis (p = 0.24) and early posttransplant reoperation (p = 0.94) that have historically contributed to poor late-allograft outcomes. Improved outcomes were associated with changes in patient characteristics and perioperative practices, which subsequently impacted both early post-LT complications as well as other sequalae known to contribute to adverse events in long-term pediatric LT recipients. In conclusion, despite significant changes in patient selection toward higher risk populations, and without notable improvement in several perioperative complications known to contribute to poor late-allograft outcomes, significant improvements in LGL and a trend toward improvement in LM was seen in a more contemporary cohort of children receiving an LT.
Assuntos
Sobrevivência de Enxerto , Transplante de Fígado , Criança , Humanos , Transplante de Fígado/métodos , Reoperação , Fatores de Risco , Transplantados , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Sarcopenia has been associated with poor surgical outcomes but has not been studied in pediatric intestinal transplantation. We aimed to determine sarcopenia prevalence in intestinal transplant recipients and the association of sarcopenia with outcomes. METHODS: We performed a cross-sectional retrospective chart review of intestinal transplant recipients from 2000-present. We estimated total psoas muscle area (tPMA) at L3-L4 and L4-L5 from computed tomography scans prior to or in the immediate peri-operative period. Sarcopenia was defined by tPMA below the 5th percentile for age and sex. We built a Cox-proportional hazards model to determine the association between sarcopenia and patient and graft survival. RESULTS: Of the 56 intestinal transplant recipients included, 36 (64%) were sarcopenic. Graft survival was 79% at one year and 59% at five years. Overall patient survival was 86% at one year and 76% at five years. Peri-transplant sarcopenia was associated with improved graft survival (Hazard ratio 0.42, 95% confidence interval: 0.20-0.88) but not overall survival (Hazard ratio 0.47, 95% confidence interval: 0.19-1.20). CONCLUSIONS: In this first report of sarcopenia in pediatric intestinal transplant, we found a high sarcopenia prevalence without an association with worse outcomes. The potential improved graft survival in sarcopenic patients along with underlying mechanisms warrant further exploration.
Assuntos
Sarcopenia , Criança , Estudos Transversais , Humanos , Prevalência , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , TransplantadosRESUMO
BACKGROUND: Acute kidney disease (AKD) is defined as impaired kidney function present for <90 days with or without an acute kidney injury (AKI) event. Adults with AKD have an increased risk for progression to chronic kidney disease (CKD) and mortality. There are no data on the epidemiology of AKD in children after transplant. The aim of this study was to evaluate the incidence and risk factors for AKI, AKD, and CKD in children after transplantation. METHODS: This is a retrospective cohort study of all children undergoing non-kidney solid organ transplant between 2011 and 2019 at UPMC Children's Hospital of Pittsburgh. AKI and AKD were defined using the Kidney Disease Improving Global Outcomes criteria. Patients with a new estimated glomerular filtration rate <60 ml/min/1.73m2 persisting for >3 months met criteria for new CKD. Variables associated with AKI, AKD, and CKD were analyzed. RESULTS: Among 338 patients, 37.9% met criteria for severe AKI, 13% for AKD, and 8% for a new diagnosis of CKD. Stage 3 AKI was independently associated with AKD (OR: 5.35; 95% CI: 2.23-12.86). Severe AKI was not associated with new-onset CKD, whereas AKD was associated with new-onset CKD (OR: 29.74; CI: 11.22-78.82). CONCLUSION: AKD may be superior to AKI in predicting risk of CKD in children after non-kidney solid organ transplantation.
Assuntos
Injúria Renal Aguda , Transplante de Órgãos , Insuficiência Renal Crônica , Doença Aguda , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Criança , Estudos de Coortes , Taxa de Filtração Glomerular , Humanos , Transplante de Órgãos/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
ABSTRACT: Pediatric acute liver failure (PALF) is a rare, rapidly progressive clinical syndrome with significant morbidity and mortality. The phenotype of PALF manifests as abrupt onset liver dysfunction, which can be brought via disparate etiology. Management is reliant upon intensive clinical care and support, often provided by the collaborative efforts of hepatologists, critical care specialists, and liver transplant surgeons. The construction of an age-based diagnostic approach, the identification of a potential underlying cause, and the prompt implementation of appropriate therapy can be lifesaving; however, the dynamic and rapidly progressive nature of PALF also demands that diagnostic inquiries be paired with monitoring strategies for the recognition and treatment of common complications of PALF. Although liver transplantation can provide a potential life-saving therapeutic option, the ability to confidently determine the certainness that liver transplant is needed for an individual child has been hampered by a lack of adequately tested clinical decision support tools and accurate predictive models. Given the accelerated progress in understanding PALF, we will provide clinical guidance to pediatric gastroenterologists and other pediatric providers caring for children with PALF by presenting the most recent advances in diagnosis, management, pathophysiology, and associated outcomes.
Assuntos
Gastroenterologia , Falência Hepática Aguda , Transplante de Fígado , Criança , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapia , América do Norte , Estado NutricionalRESUMO
The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted.
RESUMO
Chronic liver injury results in cirrhosis and end-stage liver disease (ESLD) which represents a leading cause of death worldwide, affecting people in their most productive years of life. Medical therapy can extend life, but the only definitive treatment is liver transplantation (LT). However, LT remains limited by access to quality donor organs and suboptimal long-term outcomes. The degeneration from healthy-functioning livers to cirrhosis and ESLD involves a dynamic process of hepatocyte damage, diminished hepatic function, and adaptation. However, the mechanisms responsible for deterioration of hepatocyte function and ultimately hepatic failure in man are poorly understood. We review the current understanding of cirrhosis and ESLD as a dynamic process and outline the current mechanisms associated with the development of hepatic failure from the clinical manifestations to energy adaptations, regeneration, and regulation of nuclear transcription factors. A new generation of therapeutics could target stabilization of hepatocyte differentiation and function to avoid the need for transplantation in patients with cirrhosis and ESLD.
Assuntos
Doença Hepática Terminal , Transplante de Fígado , Doença Hepática Terminal/cirurgia , Hepatócitos , Humanos , Cirrose HepáticaRESUMO
Biliary atresia (BA) is the leading indication to perform a pediatric liver transplantation (LT). Timely hepatoportoenterostomy (HPE) attempts to interrupt the natural history and allow for enteric bile flow; however, most patients who are treated with HPE require LT by the age of 10 years. We determined the cost-effectiveness of foregoing HPE to perform primary LT (pLT) in children with BA compared with standard-of-care HPE management. A Markov model was developed to simulate BA treatment over 10 years. Costs were measured in 2018 US dollars and effectiveness in life-years (LYs). The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Model parameters were derived from the literature. In the base model, we assumed similar LT outcomes after HPE and pLT. Sensitivity analyses on all model parameters were performed, including a scenario in which pLT led to 100% patient and graft survival after LT. Children undergoing HPE accumulated $316,692 in costs and 8.17 LYs per patient. Children undergoing pLT accumulated $458,059 in costs and 8.24 LYs per patient, costing $1,869,164 per LY gained compared with HPE. With parameter variation over plausible ranges, only post-HPE and post-LT costs reduced the ICER below a typical threshold of $100,000 per LY gained. On probabilistic sensitivity analysis, 93% of iterations favored HPE at that threshold. With 100% patient and graft survival after pLT, pLT cost $283,478 per LY gained. HPE is more economically favorable than pLT for BA. pLT is unfavorable even with no graft or patient loss. The ability to predict those patients who may experience high costs after HPE or low costs after LT may help identify those patients for whom pLT could be considered.