RESUMO
BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.
Assuntos
Síndrome de Alagille , Colestase , Técnicas de Imagem por Elasticidade , Hepatopatias , Humanos , Criança , Fígado/patologia , Metaloproteinase 7 da Matriz , Endoglina , Interleucina-8 , Colestase/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatias/patologia , Biomarcadores , Síndrome de Alagille/patologiaRESUMO
INTRODUCTION: The decision to become a living donor requires consideration of a complex, interactive array of factors that could be targeted for clinical, policy, and educational interventions. Our objective was to assess how financial barriers interact with motivators, other barriers, and facilitators during this process. METHODS: Data were obtained from a public survey assessing motivators, barriers, and facilitators of living donation. We used multivariable logistic regression and consensus k-means clustering to assess interactions between financial concerns and other considerations in the decision-making process. RESULTS: Among 1592 respondents, the average age was 43; 74% were female and 14% and 6% identified as Hispanic and Black, respectively. Among employed respondents (72%), 40% indicated that they would not be able to donate without lost wage reimbursement. Stronger agreement with worries about expenses and dependent care challenges was associated with not being able to donate without lost wage reimbursement (OR = 1.2, 95% CI = 1.0-1.3; OR = 1.2, 95% CI = 1.1-1.3, respectively). Four respondent clusters were identified. Cluster 1 had strong motivators and facilitators with minimal barriers. Cluster 2 had barriers related to health concerns, nervousness, and dependent care. Clusters 3 and 4 had financial barriers. Cluster 3 also had anxiety related to surgery and dependent care. CONCLUSIONS: Financial barriers interact primarily with health and dependent care concerns when considering living organ donation. Targeted interventions to reduce financial barriers and improve provider communication regarding donation-related risks are needed.
Assuntos
Tomada de Decisões , Doadores Vivos , Motivação , Obtenção de Tecidos e Órgãos , Humanos , Feminino , Masculino , Adulto , Doadores Vivos/psicologia , Obtenção de Tecidos e Órgãos/economia , Pessoa de Meia-Idade , Inquéritos e Questionários , Prognóstico , SeguimentosRESUMO
OBJECTIVES: To advance our understanding of monogenic forms of intrahepatic cholestasis. METHODS: Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data. RESULTS: Ninety-eight participants with FIC1 (nâ=â26), BSEP (nâ=â53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (nâ=â19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2âyears in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1âyear in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported. CONCLUSIONS: In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.
Assuntos
Colestase Intra-Hepática , Colestase , Transportadores de Cassetes de Ligação de ATP/genética , Criança , Pré-Escolar , Colestase/genética , Colestase Intra-Hepática/genética , Humanos , Estudos Longitudinais , MutaçãoRESUMO
Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow-up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs' NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.
Assuntos
Custos de Cuidados de Saúde , Doadores Vivos/estatística & dados numéricos , Avaliação das Necessidades/normas , Transplante de Órgãos/economia , Obtenção de Tecidos e Órgãos/economia , Viagem/economia , Financiamento Governamental , HumanosRESUMO
Osteopenia and bone fractures are significant causes of morbidity in children with cholestatic liver disease. Dual-energy X-ray absorptiometry (DXA) analysis was performed in children with intrahepatic cholestatic diseases who were enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis in the Childhood Liver Disease Research Network. DXA was performed on participants aged >5 years (with native liver) diagnosed with bile acid synthetic disorder (BASD), alpha-1 antitrypsin deficiency (A1AT), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Weight, height, and body mass index Z scores were lowest in CIC and ALGS. Total bilirubin (TB) and serum bile acids (SBA) were highest in ALGS. Bone mineral density (BMD) and bone mineral content (BMC) Z scores were significantly lower in CIC and ALGS than in BASD and A1AT (P < 0.001). After anthropometric adjustment, bone deficits persisted in CIC but were no longer noted in ALGS. In ALGS, height-adjusted and weight-adjusted subtotal BMD and BMC Z scores were negatively correlated with TB (P < 0.001) and SBA (P = 0.02). Mean height-adjusted and weight-adjusted subtotal BMC Z scores were lower in ALGS participants with a history of bone fractures. DXA measures did not correlate significantly with biliary diversion status. Conclusion: CIC patients had significant bone deficits that persisted after adjustment for height and weight and generally did not correlate with degree of cholestasis. In ALGS, low BMD and BMC reference Z scores were explained by poor growth. Anthropometrically adjusted DXA measures in ALGS correlate with markers of cholestasis and bone fracture history. Reduced bone density in this population is multifactorial and related to growth, degree of cholestasis, fracture vulnerability, and contribution of underlying genetic etiology.
Assuntos
Densidade Óssea , Colestase/etiologia , Transtornos do Crescimento/etiologia , Hepatopatias/complicações , Hepatopatias/fisiopatologia , Absorciometria de Fóton , Adolescente , Criança , Doença Crônica , Correlação de Dados , Feminino , Humanos , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND: Previous studies indicate there may be psychological consequences of being unable to serve as a living donor, but these have not been explored in a large national cohort of low-income individuals who initiated living donor evaluation in US transplant centers. METHODS: Using data from 6574 National Living Donor Assistance Center (NLDAC) participants (November 1, 2007-December 31, 2018), we utilized a cross-sectional study design to evaluate short-term depressive symptoms and satisfaction with life in living donors and non-donors (those who were declined or withdrew from evaluation) using the Satisfaction with Life Scale (SWLS) and the PHQ-8, with and without risk adjustment using linear regression. RESULTS: National Living Donor Assistance Center participants originated from 207 US transplant centers. 52% of NLDAC participants responded to the survey (n = 3423; donors = 2848 (58.6% of all donors), non-donors = 575 (33.5% of all non-donors); ncenters = 201)). Respondents were significantly older, more likely to be female, white, non-Hispanic, married, more educated, more full-time employed, and more likely to be unrelated to the recipient vs non-respondents (all, P < .001). Among survey respondents, donors were significantly younger, more likely to be non-Hispanic, employed, and related to the recipient compared to non-donors (all, P < .05). Higher PHQ-8 scores were correlated with lower SWL scores (r = -.32, P < .001). Both groups displayed high SWLS (donors vs non-donors: 27.1 vs 26.3, P = .002). Both groups had low levels of depressive symptoms overall, but donors had more symptoms than non-donors (3.5 vs 2.4, P < .001). After risk adjustment, non-donors had significantly less depressive symptoms by PHQ-8 (28% lower, P < .001), but had lower life satisfaction (1.2 points lower, P < .001). CONCLUSIONS: Donors and non-donors have high global levels of overall life satisfaction and low levels of depressive symptoms at 8 weeks after donation or denial. While small effect sizes were observed between groups in these outcomes, being a non-donor was an independent risk factor for lower life satisfaction, which warrants further evaluation.
Assuntos
Transplante de Rim , Doadores Vivos , Satisfação Pessoal , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Doadores Vivos/psicologiaRESUMO
Portal hypertension (PHT) is a major cause of morbidity and mortality in pediatric liver diseases. Thus, research into causes and disease modifiers in PHT in these conditions is vitally important. PHT is rarely directly or indirectly measured in the assessment of children with chronic liver disease. A straightforward, reproducible definition of PHT could be invaluable for consistently identifying patients with PHT and for grouping these patients according to their risk of complications from their disease. We propose the term Clinically Evident Portal Hypertension (CEPH) to denote clinical findings that demonstrate evidence of elevated portal pressure. When CEPH criteria are met, PHT is highly likely to be present, although it is likely that PHT exists for variable periods of time before meeting CEPH criteria. Use of this research definition of CEPH will allow for consistent identification of these patients by clinicians in nearly any clinical setting and serve as a clinical milepost that may dictate future prognosis in pediatric patients with cirrhosis.
Assuntos
Gastroenterologia/normas , Hipertensão Portal/diagnóstico , Pediatria/normas , Avaliação de Sintomas/normas , Terminologia como Assunto , Criança , Feminino , Gastroenterologia/métodos , Humanos , Hipertensão Portal/classificação , Fígado/irrigação sanguínea , Masculino , Pediatria/métodosRESUMO
Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow-up registry data from 1988-2014 for 379 257 recipients of first kidney-only transplants using Cox regression. Compared to the United States, 1-year adjusted graft failure risk was significantly higher in the United Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18-1.26, P < .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14-1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84-0.96, P = .001). In contrast, long-term adjusted graft failure risk (conditional on 1-year function) was significantly higher in the United States compared to Australia, New Zealand, and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001). Thus long-term kidney graft outcomes are approximately 25% worse in the United States than in 3 other countries with well-developed kidney transplant systems. Case mix differences and residual confounding from unmeasured factors were found to be unlikely explanations. These findings suggest that identification of potentially modifiable country-specific differences in care delivery and/or practice patterns should be sought.
Assuntos
Rejeição de Enxerto/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Adulto , Austrália/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized.
Assuntos
Interpretação Estatística de Dados , Falência Renal Crônica/etiologia , Estudos Observacionais como Assunto , Humanos , Tempo de Internação/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Modelos Estatísticos , Prognóstico , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for "early" hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post-LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient-year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate-adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow-up months 0-6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143-1152 2017 AASLD.
Assuntos
Doença Hepática Terminal/cirurgia , Hospitalização/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Sistema de Registros/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Idoso , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/virologia , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Estudos Longitudinais , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD.
Assuntos
Doenças dos Ductos Biliares/epidemiologia , Ductos Biliares/anatomia & histologia , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Anastomose em-Y de Roux/efeitos adversos , Anastomose em-Y de Roux/métodos , Variação Anatômica , Doenças dos Ductos Biliares/etiologia , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Estudos de Coortes , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Fígado/irrigação sanguínea , Fígado/cirurgia , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/efeitos adversos , Trombose/epidemiologia , Trombose/etiologia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Primary sclerosing cholangitis (PSC) recurs in 15%-25% of patients transplanted for PSC. In the United States, PSC transplant patients are more likely to receive an organ from a living donor (LD) than patients without PSC. Our aims were to (1) compare risk of PSC recurrence in LD versus deceased donor recipients and (2) identify risk factors for PSC recurrence. There were 241 living donor liver transplantations (LDLTs) and 65 deceased donor liver transplantation (DDLT) patients transplanted between 1998 and 2013 enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study who were evaluated. PSC recurrence risk for LDLT and DDLT recipients was compared using Kaplan-Meier survival curves and log-rank tests. Cox models were used to evaluate PSC risk factors. Overall PSC recurrence probabilities were 8.7% and 22.4% at 5 and 10 years after liver transplantation (LT), respectively. The risk of PSC recurrence was not significantly different for DDLT versus LDLT recipients (P = 0.36). For DDLT versus LDLT recipients, unadjusted 5- and 10-year PSC recurrence was 9.4% versus 9.5% and 36.9% versus 21.1%. Higher laboratory Model for End-Stage Liver Disease (MELD) score at LT, onset of a biliary complication, cholangiocarcinoma, and higher donor age were associated with increased risks of PSC recurrence: for MELD (hazard ratio [HR] = 1.06; 95% confidence interval [CI] 1.02-1.10 per MELD point, P = 0.002); for biliary complication (HR, 2.82; 95% CI, 1.28-6.25; P = 0.01); for cholangiocarcinoma (HR, 3.98; 95% CI, 1.43-11.09; P = 0.008); for donor age (per 5-years donor age; HR, 1.17; 95% CI, 1.02-1.35; P = 0.02). Factors not significantly associated with PSC recurrence included the following: first-degree relative donor (P = 0.11), post-LT cytomegalovirus infection (P = 0.38), and acute rejection (P = 0.22). Risk of recurrent PSC was not significantly different for DDLT and LDLT recipients. Biliary complications, cholangiocarcinoma, MELD, and donor age were significantly associated with risk of PSC recurrence. Liver Transplantation 22 1214-1222 2016 AASLD.
Assuntos
Colangite Esclerosante/cirurgia , Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Coleta de Tecidos e Órgãos/métodos , Adulto , Colangite Esclerosante/complicações , Colangite Esclerosante/mortalidade , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Estados UnidosRESUMO
Hyponatremia is associated with elevated wait-list mortality among end-stage liver disease candidates for liver transplantation (LT). However, the effect of low serum sodium on the survival benefit of LT has not been examined. We sought to determine whether pretransplant hyponatremia is associated with an altered LT survival benefit. Data were obtained from the Scientific Registry of Transplant Recipients. The study population consisted of adults (age ≥ 18 years) placed on the waiting list for LT between January 1, 2005 and December 31, 2012 (n = 69,213). The effect of hyponatremia on the survival benefit was assessed via sequential stratification, an extension of Cox regression. Each transplant recipient was matched to appropriate candidates then active on the waiting list with the same Model for End-Stage Liver Disease (MELD) score and in the same donation service area. The focus of the analysis was the interaction between the serum sodium and the MELD score with respect to the survival benefit of LT; this was defined as the covariate-adjusted hazard ratio contrasting post-LT mortality and pre-LT mortality. The LT survival benefit increased significantly with decreasing serum sodium values when the MELD scores were >11. The survival benefit of LT was not affected by serum sodium for patients with MELD scores ≤ 11. In conclusion, the LT survival benefit (or lack thereof) is independent of serum sodium for patients with MELD scores ≤ 11. The increase in the survival benefit with decreasing serum sodium among patients with MELD scores > 11 is consistent with recently approved changes to the allocation system incorporating serum sodium.
Assuntos
Doença Hepática Terminal/cirurgia , Hiponatremia/sangue , Transplante de Fígado , Sódio/sangue , Adulto , Biomarcadores/sangue , Técnicas de Apoio para a Decisão , Doença Hepática Terminal/sangue , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Hiponatremia/diagnóstico , Hiponatremia/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Obtenção de Tecidos e Órgãos , Resultado do Tratamento , Estados Unidos , Listas de EsperaRESUMO
BACKGROUND: Many have advocated the preferential use of high risk allografts for hepatocellular carcinoma patients undergoing liver transplantation. Hepatocellular carcinoma (HCC) patients tend to have relatively preserved liver function, and their outcome is felt to be driven largely by tumor-related factors. AIM: The aim of this study was to compare the relative importance of donor versus recipient factors on post-orthotopic liver transplantation survival among HCC and non-HCC recipients. METHODS: The study group included Scientific Registry of Transplant Recipients data on adult recipients of deceased donor liver transplants from February 2002 through December 2008. Recipients were classified as HCC based on MELD exception applications and were compared to all other recipients. Predictors of post-LT survival were identified by Cox regression. To test whether donor factors have less impact on survival in HCC patients, interaction terms were created between HCC diagnosis and donor factors. RESULTS: Of the 40,212 DDLTs during the study period, 29,020 (72 %) met study criteria. A total of 7,786 (27 %)were transplanted with a diagnosis of HCC. The mean donor risk index was 1.5 in both cohorts. The 1-/5-year survival was 88 %/68 % and 87 %/74 % among HCC and non-HCC recipients, respectively (p\0.0001). On multivariate analysis, there was no statistically significant interaction between HCC diagnosis and DRI (HR 0.94,p = 0.317). Likewise, no interaction was seen between HCC diagnosis and individual donor factors. In both groups, donor and recipient factors carried similar weight in determining post-LT survival. CONCLUSIONS: Contrary to previous assumptions, donor factors play a similar role in determining survival post-LT among HCC patients and non-HCC patients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Doadores de Tecidos , Adulto , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
UNLABELLED: Porto-pulmonary hypertension (POPH), once considered an absolute contraindication for liver transplantation (LT), has become a more accepted indication because of the evolution of treatment with prostacyclin analogues, phosphodiesterase inhibitors and endothelin receptor antagonists. An exception model for end stage liver disease (MELD) score of 22 is assigned to candidates with documentation of effective treatment. We examined the post-transplant outcomes of patients who received LT for POPH with exception. METHODS: Scientific Registry of Transplant Recipients data on 34,318 adult (≥ 18 years) deceased donor LT recipients transplanted between March 1, 2002 and August 31, 2010 were reviewed. The diagnosis of POPH was ascertained from MELD exception forms. Patients were followed from the time of transplant until the earlier occurrence of death or end of the follow-up period. Cox regression was used to evaluate the predictors of post-LT mortality and graft failure. RESULTS: During the study period, 34,318 patients received deceased donor LT. Seventy eight out of 34,318 patients were transplanted for POPH with MELD exception. The 1-year adjusted risks of patient death and graft failure for patients transplanted under exception rules for POPH were significantly higher than with POPH adult recipients who did not receive exception points (death:hazard ratio [HR] = 2.25, p = 0.005 and graft failure HR = 1.96, p = 0.012). CONCLUSIONS: This study of national data suggests that treated POPH continues to be associated with inferior early post-transplant outcomes.
Assuntos
Doença Hepática Terminal/complicações , Hipertensão Portal/complicações , Hipertensão Pulmonar/complicações , Transplante de Fígado/mortalidade , Índice de Gravidade de Doença , Doença Hepática Terminal/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Incident ESRD after liver transplantation (LT) is associated with high post-transplant mortality. We constructed and validated a continuous renal risk index (RRI) to predict post-LT ESRD. Data for 43,514 adult recipients of deceased donor LT alone (February 28, 2002 to December 31, 2010) were linked from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services ESRD Program. An adjusted Cox regression model of time to post-LT ESRD was fitted, and the resulting equation was used to calculate an RRI for each LT recipient. The RRI included 14 recipient factors: age, African-American race, hepatitis C, cholestatic disease, body mass index ≥ 35, pre-LT diabetes, ln creatinine for recipients not on dialysis, ln albumin, ln bilirubin, serum sodium<134 mEq/L, status-1, previous LT, transjugular intrahepatic portosystemic shunt, and acute dialysis at LT. This RRI was validated and had a C statistic of 0.76 (95% confidence interval, 0.75 to 0.78). Higher RRI associated significantly with higher 5-year cumulative incidence of ESRD and post-transplant mortality. In conclusion, the RRI constructed in this study quantifies the risk of post-LT ESRD and is applicable to all LT alone recipients. This new validated measure may serve as an important prognostic tool in ameliorating post-LT ESRD risk and improve survival by informing post-LT patient management strategies.
Assuntos
Falência Renal Crônica/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Cadáver , Feminino , Humanos , Incidência , Masculino , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Introduction: Living donation increases the organ supply, but associated non-medical expenses can disincentivize donation. Programs aimed at increasing living donation need to better understand how financial obstacles, including lost wages, impact the decision to pursue donation. Methods/Approach: Forty-eight interviews were conducted and analyzed using a grounded theory approach. Findings: Three key themes were identified that influenced decision-making: emotional attachment, temporal flexibility, and job security. These themes emerged when dividing interview participants into 3 groups: close relationship donors, broader network donors, and non-directed donors, representing donation to a family member or friend, a specific person they do not know well or at all, or a non-specified individual, respectively. Most close relationship donors wanted to donate regardless of personal financial cost, based on emotional attachment to the recipient. Wage reimbursement did not typically affect their decision-making but could reduce stress. Since non-directed donors did not donate to a specific individual, they could wait to achieve financial stability before donating, if needed. While wage reimbursement might create more proximate stability, non-directed donors had the flexibility to postpone donations until they could independently achieve financial stability. Lacking emotional attachment and temporal flexibility, broader network donors were particularly active decision-makers and most influenced by wage reimbursement. Across all groups, donors with job security were more resolute about donating. Conclusion: The findings underscore the importance of lost wage reimbursement to facilitate donation and reduce stress, and policies to protect donor job security.
RESUMO
We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P<0.001), 0.88±0.15 for galactose (P=0.07), 0.84±0.08 for PHM (P=0.002), and 0.83±0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown.
Assuntos
Hepatectomia , Regeneração Hepática , Transplante de Fígado/métodos , Fígado/cirurgia , Doadores Vivos , Adulto , Alanina Transaminase/sangue , Bilirrubina/sangue , Testes Respiratórios , Cafeína/sangue , Colatos/sangue , Colorado , Eritromicina/metabolismo , Feminino , Humanos , Coeficiente Internacional Normatizado , Modelos Lineares , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/metabolismo , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , São Francisco , Albumina Sérica/metabolismo , Albumina Sérica Humana , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Adult recipients of living donor liver transplantation (LDLT) have a higher incidence of biliary complications than recipients of deceased donor liver transplantation (DDLT). Our objective was to define the intensity of the interventions and the time to resolution after the diagnosis of biliary complications after liver transplantation. We analyzed the management and resolution of posttransplant biliary complications and investigated the comparative effectiveness of interventions in LDLT and DDLT recipients. For the analysis of biliary complications (leaks or strictures), we used a retrospective cohort of patients who underwent liver transplantation at 8 centers between 1998 and 2006 (median follow-up from onset=4.7 years). The numbers, procedure types, and times to resolution were compared for LDLT and DDLT recipients. Posttransplant biliary complications occurred in 47 of the 189 DDLT recipients (25%) and in 141 of the 356 LDLT recipients (40%). Biliary leaks constituted 38% of the post-DDLT biliary complications (n=18) and 65% of the post-LDLT biliary complications (n=91). The median times to first biliary complications were similar for DDLT and LDLT (11 versus 14 days for leaks, P=0.63; 69 versus 107 days for strictures, P=0.34). Overall, 1225 diagnostic and therapeutic procedures, including reoperation and retransplantation, were performed (6.5±5.4 per recipient; 5.5±3.6 for DDLT versus 6.8±5.8 for LDLT, P=0.52). The median number of months to the resolution of a biliary complication (i.e., a tube-, stent-, and drain-free status) did not significantly differ between the DDLT and LDLT groups for leaks (2.3 versus 1.3 months, P=0.29) or strictures (4.9 versus 2.3 months, P=0.61). Although the incidence of biliary complications is higher after LDLT versus DDLT, the treatment requirements and the time to resolution after the development of a biliary complication are similar for LDLT and DDLT recipients.
Assuntos
Fístula Anastomótica/cirurgia , Colestase/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Adulto , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/mortalidade , Distribuição de Qui-Quadrado , Colestase/diagnóstico , Colestase/mortalidade , Constrição Patológica , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes. METHODS: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Relationships between eSMM, liver disease, and transplant-free survival were assessed. RESULTS: eSMM was calculated in 127 participants (5-18 y): 12 BASD, 41 a1ATd, 33 CIC, and 41 ALGS. eSMM z-score was lower in CIC (-1.6 ± 1.3) and ALGS (-2.1 ± 1.0) than BASD (-0.1 ± 1.1) and a1ATd (-0.5 ± 0.8, p < 0.001). Sarcopenia (defined as eSMM z-score ≤- 2) was present in 33.3% of CIC and 41.5% of ALGS participants. eSMM correlated with bone mineral density in the 4 disease groups (r=0.52-0.55, p < 0.001-0.07), but not serum bile acids, bilirubin, aspartate aminotransferase/platelet ratio index, or clinically evident portal hypertension. Of the 2 patients who died (1 with sarcopenia) and 18 who underwent liver transplant (LT, 4 with sarcopenia), eSMM z-score did not predict transplant-free survival. eSMM z-score correlated with the Physical Pediatric Quality of Life Inventory score (r=0.38-0.53, p = 0.007-0.04) in CIC and a1ATd. CONCLUSION: Severe sarcopenia occurs in some children with ALGS and CIC. The lack of correlation between eSMM and biochemical cholestasis suggests mechanisms beyond cholestasis contribute to sarcopenia. While sarcopenia did not predict transplant-free survival, LT and death were infrequent events. Future studies may define mechanisms of sarcopenia in genetic intrahepatic cholestasis.