RESUMEN
Acute-on-chronic liver failure (ACLF) is a variably defined syndrome characterized by acute decompensation of cirrhosis with organ failures. At least 13 different definitions and diagnostic criteria for ACLF have been proposed, and there is increasing recognition that patients with ACLF may face disadvantages in the current United States liver allocation system. There is a need, therefore, for more standardized data collection and consensus to improve study design and outcome assessment in ACLF. In this article, we discuss the current landscape of transplantation for patients with ACLF, strategies to optimize organ utility, and data opportunities based on emerging technologies to facilitate improved data collection.
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Candidates for multivisceral transplant (MVT) have experienced decreased access to transplant in recent years. Using Organ Procurement and Transplantation Network data, transplant and waiting list outcomes for MVT (ie, liver-intestine, liver-intestine-pancreas, and liver-intestine-kidney-pancreas) candidates listed between February 4, 2018, and February 3, 2022, were analyzed, including model for end-stage liver disease/pediatric end-stage liver disease and exception scores by era (before and after acuity circle [AC] implementation on February 4, 2020) and age group (pediatric and adult). Of 284 MVT waitlist registrations (45.6% pediatric), fewer had exception points at listing post-AC compared to pre-AC (10.0% vs 19.1%), and they were less likely to receive transplant (19.1% vs 35.9% at 90 days; 35.7% vs 57.2% at 1 year). Of 177 MVT recipients, exception points at transplant were more common post-AC compared to pre-AC (30.8% vs 20.2%). Postpolicy, adult MVT candidates were more likely to be removed due to death/too sick compared with liver-alone candidates (13.5% vs 5.6% at 90 days; 24.2% vs 9.8% at 1 year), whereas no excess waitlist mortality was observed among pediatric MVT candidates. Under current allocation policy, multivisceral candidates experience inferior waitlist outcomes compared with liver-alone candidates. Clarification of guidance around submission and approval of multivisceral exception requests may help improve their access to transplantation and achieve equity between multivisceral and liver-alone candidates on the liver transplant waiting list.
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Trasplante de Hígado , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Listas de Espera/mortalidad , Obtención de Tejidos y Órganos/estadística & datos numéricos , Trasplante de Hígado/mortalidad , Masculino , Adulto , Niño , Femenino , Intestinos/trasplante , Adolescente , Estudios de Seguimiento , Preescolar , Donantes de Tejidos/provisión & distribución , Tasa de Supervivencia , Pronóstico , Persona de Mediana Edad , Adulto Joven , Lactante , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Asignación de RecursosRESUMEN
In 2022, liver transplant activity continued to increase in the United States, with an all-time high of 9,527 transplants performed, representing a 52% increase over the past decade (2012-2022). Of these transplants, 8,924 (93.7%) were from deceased donors and 603 (6.3%) were from living donors. Liver transplant recipients were 94.5% adult and 5.5% pediatric. The overall size of the liver transplant waiting list contracted, with more patients being removed than added, although 10,548 adult patients still remained on the waiting list at the end of 2022. Alcohol-associated liver disease continued to be the leading diagnosis among both candidates and recipients, followed by metabolic dysfunction-associated steatohepatitis. Simultaneous liver-kidney transplant was the most common multiorgan combination, with 800 liver-kidney transplants performed in 2022; in addition, there were 303 new listings for kidney transplant via the safety net mechanism. Among adults added to the liver waiting list in 2021, 39.9% received a deceased donor liver transplant within 3 months; 45.7%, within 6 months; and 54.5%, within 1 year. Pretransplant mortality decreased to 12.3 deaths per 100 patient-years in 2022, although still 15.6% of removals from the waiting list were for death or being too sick for transplant. Graft and patient survival outcomes after deceased donor liver transplant improved, approximating pre-COVID-19 pandemic levels, with 5.1% mortality observed at 6 months; 6.8%, at 1 year; 12.7%, at 3 years; 19.8%, at 5 years; and 35.7%, at 10 years. Five-year graft and patient survival rates after living donor liver transplant exceeded those of deceased donor liver transplant. Candidates receiving model for end-stage liver disease exception points for hepatocellular carcinoma constituted 15.5% of transplants performed in 2022, with similar transplant rates and posttransplant outcomes compared to cases without hepatocellular carcinoma exception. In 2022, more pediatric liver transplant candidates were added to the waiting list and underwent transplant compared with either of the preceding 2 years, with an uptick in living donor liver transplant volume. Although pretransplant mortality has improved after the recent policy change prioritizing pediatric donors for pediatric recipients, still, in 2022, 50 children died or were removed from the waiting list for being too sick to undergo transplant. Posttransplant mortality among pediatric liver transplant recipients remained notable, with death occurring in 4.0% at 6 months, 6.0% at 1 year, 8.2% at 3 years, 9.8% at 5 years, and 13.9% at 10 years. Similar to adult living donor recipients, pediatric living donor recipients had better 5-year patient survival compared with deceased donor recipients.
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Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto , Humanos , Niño , Estados Unidos/epidemiología , Donadores Vivos , Pandemias , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Listas de Espera , Supervivencia de InjertoRESUMEN
BACKGROUND & AIMS: Continuous risk-stratification of candidates and urgency-based prioritization have been utilized for liver transplantation (LT) in patients with non-hepatocellular carcinoma (HCC) in the United States. Instead, for patients with HCC, a dichotomous criterion with exception points is still used. This study evaluated the utility of the hazard associated with LT for HCC (HALT-HCC), an oncological continuous risk score, to stratify waitlist dropout and post-LT outcomes. METHODS: A competing risk model was developed and validated using the UNOS database (2012-2021) through multiple policy changes. The primary outcome was to assess the discrimination ability of waitlist dropouts and LT outcomes. The study focused on the HALT-HCC score, compared with other HCC risk scores. RESULTS: Among 23,858 candidates, 14,646 (59.9%) underwent LT and 5196 (21.8%) dropped out of the waitlist. Higher HALT-HCC scores correlated with increased dropout incidence and lower predicted 5-year overall survival after LT. HALT-HCC demonstrated the highest area under the curve (AUC) values for predicting dropout at various intervals post-listing (0.68 at 6 months, 0.66 at 1 year), with excellent calibration (R2 = 0.95 at 6 months, 0.88 at 1 year). Its accuracy remained stable across policy periods and locoregional therapy applications. CONCLUSIONS: This study highlights the predictive capability of the continuous oncological risk score to forecast waitlist dropout and post-LT outcomes in patients with HCC, independent of policy changes. The study advocates integrating continuous scoring systems like HALT-HCC in liver allocation decisions, balancing urgency, organ utility, and survival benefit.
RESUMEN
The exception point system for liver allocation in the United States allows for additional waitlist priority for candidates where the Model for End-Stage Liver Disease or Pediatric End-stage Liver Disease does not effectively represent their urgency or need for a transplant. In May 2019, the review process for liver exception cases transitioned from 11 Regional Review Boards (RRBs) to 1 National Liver Review Board (NLRB), intended to increase consistency nationwide, improve efficiency, and balance transplant access for candidates with and without exception scores. This report provides a review of liver exception request and review practices, waitlist outcomes, and transplant activity in the first 2 years after implementation of the NLRB and acuity circle-based distribution in the United States. We compared initial and extension exception request forms submitted from May 13, 2017 to May 13, 2019 (prepolicy or RRB era) to the period from February 4, 2020 to February 3, 2022 (postpolicy or NLRB era). During this time, the NLRB reviewed 10,083 initial exception requests and 12,686 extension requests. Notable postpolicy highlights include (1) an increase in the proportion of initial and extension requests that were automatically approved instead of manually reviewed; (2) a decrease in the overall approval rates of initial exception requests (87.8% for adult HCC, 64.3% for adult other diagnoses, and 71.5% for pediatric); and (3) reduction in the time from exception request submission to adjudication to a median of 3.73 days. The proportions of waitlist registration and deceased donor liver transplants for patients with exception scores decreased, and waitlist outcomes between patients with and without exception scores are now comparable. Implementation of the NLRB improved efficiency, reduced case workloads, and standardized criteria for exception cases, with similar waitlist outcomes between patients with and without exception scores and improved equity in terms of access to liver transplants.
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Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto , Humanos , Niño , Estados Unidos , Carcinoma Hepatocelular/diagnóstico , Enfermedad Hepática en Estado Terminal/cirugía , Neoplasias Hepáticas/diagnóstico , Trasplante de Hígado/efectos adversos , Selección de Paciente , Índice de Severidad de la Enfermedad , Donadores Vivos , Listas de EsperaRESUMEN
BACKGROUND AND AIMS: Adolescents constitute a unique waitlist cohort that is distinct from younger children. Model for End-stage Liver Disease (MELD) 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Sodium in the current liver allocation system for both adults and adolescents aged 12-17. We evaluated the predictive performance of MELD-Sodium, MELD 3.0, and Pediatric End-stage Liver Disease for 90-day waitlist mortality risk among adolescent liver transplant registrants. APPROACH AND RESULTS: New waitlist registrations for primary liver transplants among individuals aged 12-17 and 18-25 for comparison were identified using Organ Procurement and Transplantation Network (OPTN) data from November 17, 2004, to December 31, 2021. The predictive performance of the current and proposed MELD and Pediatric End-stage Liver Disease scores was assessed using Harrell's concordance ( c ) statistic. There were 1238 eligible listings for adolescents aged 12-17 and 1740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared with 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR=1.27, 95% CI: 1.18-1.37), and the c -statistic for 90-day waitlist survival using MELD 3.0 was 0.893 compared with 0.871 using MELD-Sodium and 0.852 using Pediatric End-stage Liver Disease. CONCLUSIONS: The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplants.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto Joven , Humanos , Adolescente , Niño , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Índice de Severidad de la Enfermedad , Listas de Espera , SodioRESUMEN
BACKGROUND: NAFLD is common in primary care. Liver fibrosis stage 2 or higher (≥F2) increases future risk of morbidity and mortality. We developed and validated a score to aid in the initial assessment of liver fibrosis for NAFLD in primary care. METHODS: Data from patients with biopsy-proven NAFLD were extracted from the NASH Clinical Research Network observational study ( n = 676). Using logistic regression and machine-learning methods, we constructed prediction models to distinguish ≥F2 from F0/1. The models were tested in participants in a trial ("FLINT," n = 280) and local patients with NAFLD with magnetic resonance elastography data ( n = 130). The final model was applied to examinees in the National Health and Nutrition Examination Survey (NHANES) III ( n = 11,953) to correlate with long-term mortality. RESULTS: A multivariable logistic regression model was selected as the Steatosis-Associated Fibrosis Estimator (SAFE) score, which consists of age, body mass index, diabetes, platelets, aspartate and alanine aminotransferases, and globulins (total serum protein minus albumin). The model yielded areas under receiver operating characteristic curves ≥0.80 in distinguishing F0/1 from ≥F2 in testing data sets, consistently higher than those of Fibrosis-4 and NAFLD Fibrosis Scores. The negative predictive values in ruling out ≥F2 at SAFE of 0 were 88% and 92% in the two testing sets. In the NHANES III set, survival up to 25 years of subjects with SAFE < 0 was comparable to that of those without steatosis ( p = 0.34), whereas increasing SAFE scores correlated with shorter survival with an adjusted HR of 1.53 ( p < 0.01) for subjects with SAFE > 100. CONCLUSION: The SAFE score, which uses widely available variables to estimate liver fibrosis in patients diagnosed with NAFLD, may be used in primary care to recognize low-risk NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Encuestas Nutricionales , Cirrosis Hepática/patología , Fibrosis , Biopsia , Atención Primaria de Salud , Hígado/patologíaRESUMEN
BACKGROUND: Donors with hyperbilirubinemia are often not utilized for liver transplantation (LT) due to concerns about potential liver dysfunction and graft survival. The potential to mitigate organ shortages using such donors remains unclear. METHODS: This study analyzed adult deceased donor data from the United Network for Organ Sharing database (2002-2022). Hyperbilirubinemia was categorized as high total bilirubin (3.0-5.0 mg/dL) and very high bilirubin (≥5.0 mg/dL) in brain-dead donors. We assessed the impact of donor hyperbilirubinemia on 3-month and 3-year graft survival, comparing these outcomes to donors after circulatory death (DCD). RESULTS: Of 138 622 donors, 3452 (2.5%) had high bilirubin and 1999 (1.4%) had very high bilirubin levels. Utilization rates for normal, high, and very high bilirubin groups were 73.5%, 56.4%, and 29.2%, respectively. No significant differences were found in 3-month and 3-year graft survival between groups. Donors with high bilirubin had superior 3-year graft survival compared to DCD (hazard ratio .83, p = .02). Factors associated with inferior short-term graft survival included recipient medical condition in intensive care unit (ICU) and longer cold ischemic time; factors associated with inferior long-term graft survival included older donor age, recipient medical condition in ICU, older recipient age, and longer cold ischemic time. Donors with ≥10% macrosteatosis in the very high bilirubin group were also associated with worse 3-year graft survival (p = .04). DISCUSSION: The study suggests that despite many grafts with hyperbilirubinemia being non-utilized, acceptable post-LT outcomes can be achieved using donors with hyperbilirubinemia. Careful selection may increase utilization and expand the donor pool without negatively affecting graft outcome.
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Hígado , Obtención de Tejidos y Órganos , Adulto , Humanos , Pronóstico , Donantes de Tejidos , Supervivencia de Injerto , Hiperbilirrubinemia/etiología , Bilirrubina , Estudios RetrospectivosRESUMEN
In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.
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COVID-19 , Hepatopatías Alcohólicas , Neoplasias Hepáticas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto , Niño , Humanos , Estados Unidos/epidemiología , Donadores Vivos , Pandemias , Supervivencia de Injerto , COVID-19/epidemiología , Donantes de Tejidos , Listas de EsperaRESUMEN
Standard eligibility criteria for simultaneous liver-kidney transplantation (SLK) are in place in the United States. We hypothesize that the benefit associated with SLK over liver transplant alone differs by patient, depending on the specific SLK criteria met. We analyzed a retrospective US cohort of 5446 adult liver transplant or SLK recipients between January 1, 2015, and December 31, 2018, who are potentially qualified for SLK. Exposure was a receipt of SLK. We tested effect modification by the specific SLK eligibility criteria met (end-stage kidney disease, acute kidney injury, chronic kidney disease, or unknown). The primary outcome was death within 1 year of a liver transplant. We used a modified Cox regression analysis containing an interaction term of SLK * time from transplant. Two hundred ten (9%) SLK recipients and 351 (11%) liver-alone recipients died in 1 year. In the overall population, SLK was associated with a mortality benefit over liver transplant on the day of the transplant, without adjustment [HR: 0.59 (95% CI, 0.46-0.76)] and with adjustment [aHR: 0.50 (95% CI, 0.35-0.71)]. However, when SLK eligibility criteria were included, only in patients with end-stage kidney disease was SLK associated with a sustained survival benefit at day 0 [HR: 0.17 (0.08-0.35)] up to 288 (95% CI, 120-649) days post-transplant. Benefit within the first year post-transplant associated with SLK over liver-alone transplantation was only pronounced in patients with end-stage kidney disease but not present in patients meeting other criteria for SLK. A "strict SLK liberal Safety Net" strategy may warrant consideration at the national policy level.
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Fallo Renal Crónico , Trasplante de Riñón , Trasplante de Hígado , Adulto , Humanos , Estados Unidos/epidemiología , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , HígadoRESUMEN
In this review article, we discuss the model for end-stage liver disease (MELD) score and its dual purpose in general and transplant hepatology. As the landscape of liver disease and transplantation has evolved considerably since the advent of the MELD score, we summarise emerging concepts, methodologies, and technologies that may improve mortality prognostication in the future. Finally, we explore how these novel concepts and technologies may be incorporated into clinical practice.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Índice de Severidad de la Enfermedad , Listas de EsperaRESUMEN
BACKGROUND & AIMS: Policy changes in the United States have lengthened overall waiting times for patients with hepatocellular carcinoma (HCC). We investigated temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the United States. METHODS: Data for primary adult LT candidates listed from 2003 to 2018 who received HCC exception were extracted from the Organ Procurement and Transplantation Network database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout. RESULTS: There were 31,609 eligible patients with at least 1 approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least 1 LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. An increased incidence of LRT was observed among patients with tumor burden beyond Milan criteria, higher α-fetoprotein level, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there was no significant difference by number of LRTs. In inverse probability of treatment weighting-adjusted analysis, radioembolization or ablation as the first LRT was associated with a reduced risk of waitlist dropout compared with chemoembolization. CONCLUSIONS: In a large nationwide cohort of LT candidates with HCC, LRT, and in particular radioembolization, increasingly was used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Carga Tumoral , Estados Unidos/epidemiología , Listas de EsperaRESUMEN
BACKGROUND & AIMS: The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. METHODS: All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. RESULTS: The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02). CONCLUSION: MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.
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Técnicas de Apoyo para la Decisión , Enfermedad Hepática en Estado Terminal/diagnóstico , Trasplante de Hígado , Listas de Espera , Bilirrubina/sangre , Biomarcadores/sangre , Toma de Decisiones Clínicas , Creatinina/sangre , Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Disparidades en Atención de Salud , Humanos , Relación Normalizada Internacional , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Sodio/sangre , Factores de Tiempo , Estados Unidos , Listas de Espera/mortalidadRESUMEN
INTRODUCTION: Alcohol-related liver disease (ALD) is now the leading indication for liver transplantation (LT) in the United States (US). It remains unclear how centers are managing the medical and psychosocial issues associated with these patients. METHODS: We conducted a web-based survey of LT centers in the United States to identify center-level details on peri-LT management of ALD and related issues. RESULTS: Of the 117 adult LT centers, 100 responses (85.5%) were collected, representing all Organ Procurement and Transplantation Network regions. For alcohol-associated cirrhosis, 70.0% of the centers reported no minimum sobriety requirement while 21.0% required 6 months of sobriety. LT for severe alcohol-associated hepatitis was performed at 85.0% of the centers. Monitoring protocols for pre-LT and post-LT alcohol use varied among centers. DISCUSSION: Our findings highlight a change in center attitudes toward LT for ALD, particularly for severe alcohol-associated hepatitis.
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Hepatitis Alcohólica , Hepatopatías Alcohólicas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/cirugía , Humanos , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/cirugía , Recurrencia , Estados Unidos/epidemiologíaRESUMEN
Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1ß in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.
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Alcoholismo/sangre , Infecciones por VIH/sangre , Hepatitis C/sangre , Factor de Necrosis Tumoral alfa/sangre , Sustancia Blanca/patología , Alcoholismo/complicaciones , Comorbilidad , Femenino , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Análisis de Componente Principal , SolubilidadRESUMEN
In the United States, centers performing liver transplant (LT) are primarily evaluated by patient survival within 1 year after LT, but tight clustering of outcomes allows only a narrow window for evaluation of center variation for quality improvement. Alternate measures more relevant to patients and the transplant community are needed. We examined adults listed for LT in the United States, using data submitted to the Scientific Registry of Transplant Recipients. Intention-to-treat (ITT) survival was defined as survival within 1 year from listing, regardless of transplant. Mixed effects/frailty models were used to assess center variation in ITT survival. Between January 2010 and December 2016, there were 66,428 new listings at 113 centers. Overall, median 1-year ITT survival was 79.8% (interquartile range [IQR], 76.1%-83.4%), whereas 1-year waiting-list (WL) survival was 75.8% (IQR, 71.2%-79.4%), and 1-year post-LT survival was 90.0% (IQR, 87.9%-91.8%). Higher rates of ITT mortality were correlated with increased WL mortality (correlation, r = 0.76), increased post-LT mortality (r = 0.31), lower volume centers (r = -0.34), and lower transplant rate ratio (r = -0.25). Similar patterns were observed in the subgroup of WL candidates listed with Model for End-Stage Liver Disease (MELD) ≥25: median 1-year ITT survival was 65.2% (IQR, 60.2%-72.6%), whereas 1-year post-LT survival was 87.5% (IQR, 84.0%-90.9%), and 1-year WL survival was 36.6% (IQR, 27.9%-47.0%). In mixed effects modeling, the transplant center was an independent predictor of ITT survival even after adjustment for age, sex, MELD, and sociodemographic variables. Center variation for ITT survival was larger compared with post-LT survival. The measurement of ITT outcome offers a complementary method to assess center performance. This is a first step toward understanding differences in program quality beyond patient and graft survival after LT.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Análisis de Intención de Tratar , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología , Listas de EsperaRESUMEN
The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Anciano , Enfermedad Hepática en Estado Terminal/epidemiología , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Hígado/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Although most large nonpedunculated colorectal lesions can be safely and efficaciously removed using EMR, the use of colectomy for benign colorectal lesions appears to be increasing. The reason(s) is unclear. We aimed to determine the use and adverse events of EMR in the United States. METHODS: We used Optum's de-identified Clinformatics Data Mart Database (2003-2016), a database from a large national insurance provider, to identify all colonoscopies performed with either EMR or simple polypectomy on adult patients from January 1, 2011 to December 31, 2015. We measured time trends, regional variation, and adverse event rates. We assessed risk factors for adverse events using multivariate logistic regression. RESULTS: The rate of EMR use in the US increased from 1.62% of all colonoscopies in 2011 to 2.48% of colonoscopies in 2015 (P < .001). There were, however, significant regional differences in the use of EMRs, from 2.4% of colonoscopies in the western United States to 2.0% of colonoscopies in the southern United States. Between 2011 and 2015, we found stable rates of perforation, GI bleeding (GIB), infections, and cardiac adverse events and decreasing rates of admissions after EMR. In our multivariate model, EMR was an independent risk factor for adverse events, albeit the rates of adverse events were low (1.35% GIB, .22% perforation). CONCLUSIONS: Use of EMR is rising in the United States, although there is significant regional variation. The rates of adverse events after EMR and polypectomies were low and stable, confirming the continued safety of EMR procedures. A better understanding of the regional barriers and facilitators may improve the use of EMR as the standard management for benign colorectal lesions throughout the United States.
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Pólipos del Colon/cirugía , Colonoscopía/estadística & datos numéricos , Resección Endoscópica de la Mucosa/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Pólipos del Colon/patología , Colonoscopía/efectos adversos , Bases de Datos Factuales , Resección Endoscópica de la Mucosa/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Utilización de Procedimientos y Técnicas , Estudios Retrospectivos , Factores de Tiempo , Estados UnidosRESUMEN
In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.