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1.
Proc Natl Acad Sci U S A ; 120(40): e2305075120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748069

RESUMO

Enforcement is a challenge for effective international cooperation. In human rights and environmental law, along with many other domains of international cooperation, "naming and shaming" is often used as an enforcement mechanism in the absence of stronger alternatives. Naming and shaming hinges on the ability to identify countries whose efforts are inadequate and effectively shame them toward better behavior. Research on this approach has struggled to identify factors that explain when it influences state behavior in ways that lead to more cooperation. Via survey of a large (N = 910) novel sample of experienced diplomats involved in the design of the Paris Agreement, we find support for the proposition that naming and shaming is most accepted and effective in influencing the behavior of countries that have high-quality political institutions, strong internal concern about climate change, and ambitious and credible international climate commitments. Naming and shaming appears less effective in other countries, so further enforcement mechanisms will be needed for truly global cooperation. We also find that the climate diplomacy experts favor a process of naming and shaming that relies on official intergovernmental actors, in contrast with studies suggesting that NGOs, media, and other private actors are more effective at naming and shaming. We suggest that these tensions-the inability for naming and shaming to work effectively within the countries least motivated for climate action and the preference for namers and shamers that seem least likely to be effective-will become central policy debates around making cooperation on climate change more enforceable.


Assuntos
Mudança Climática , Empregados do Governo , Humanos , Cooperação Internacional , Paris , Vergonha
2.
Liver Transpl ; 30(5): 544-554, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38240602

RESUMO

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.


Assuntos
Transplante de Fígado , Criança , Humanos , Terapia de Imunossupressão , Doadores Vivos
3.
Curr Opin Organ Transplant ; 29(1): 3-9, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38032256

RESUMO

PURPOSE OF REVIEW: We review existing and newer strategies for treatment and surveillance of hepatocellular carcinoma (HCC) both pre and postliver transplantation. SUMMARY: HCC is rising in incidence and patients are often diagnosed at later stages. Consequently, there is a need for treatment strategies which include collaboration of multiple specialties. Combinations of locoregional, systemic, and surgical therapies are yielding better postliver transplantation (post-LT) outcomes for patients with HCC than previously seen. Tumor biology (tumor size, number, location, serum markers, response to therapy) can help identify patients who are at high risk for HCC recurrence posttransplantation and may expand transplant eligibility for some patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Incidência , Recidiva Local de Neoplasia
4.
Artigo em Inglês | MEDLINE | ID: mdl-37949334

RESUMO

Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD).1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g).1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD).1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States.

5.
J Clin Gastroenterol ; 57(10): 1016-1023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36226999

RESUMO

GOALS: Determine factors associated with Irritable bowel syndrome (IBS) in nonalcoholic fatty liver disease (NAFLD) patients. BACKGROUND: IBS affects 10% to 15% of the adult population worldwide and is linked to anxiety and depression. The impact of IBS-type symptoms in NAFLD patients is not well described. STUDY: A cross-sectional study of patients in the hepatology clinic at Houston Methodist Hospital was performed based on a respondent postal survey. IBS was defined by the Rome IV questionnaire, anxiety and depression were assessed with the Hospital Anxiety Depression scale. Patients with inflammatory bowel disease, colorectal carcinoma, or small bowel tumors were excluded. Patients were divided based on Rome IV diagnostic criteria for IBS and Hospital Anxiety Depression scale. RESULTS: 130 patients were included in the analysis, 38 satisfied Rome IV criteria for IBS (IBS group) versus 92 who did not (non-IBS group). Depression was more prevalent in the IBS group (18.4% vs 5.4%, P =0.01). Anxiety was also greater in the IBS group (31.6% vs 9.8%, P =0.002). Female sex, depression, and body mass index (BMI)>30 were independent predictors of IBS in NAFLD in 4 multiple logistic regression models. In newly diagnosed IBS patients, gamma-glutamyl transferase levels were lower (67.5 vs 28, P =0.04). Current abdominal pain was higher than 100% versus 81.3% ( P =0.045), as was pain associated with the change in stool frequency (96.3% vs 50%; P <0.001). CONCLUSION: Our study highlights the increased rate of IBS symptoms, depression, and anxiety in patients with NAFLD. Clinicians should be alert when IBS symptoms are reported by a NAFLD patient and be aware of the impact of these comorbidities on quality of life and response to therapy.

6.
Nature ; 609(7928): 673-675, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36114304
7.
Am J Transplant ; 22(3): 823-832, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34856069

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Transplante de Fígado , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Terapia Neoadjuvante/métodos
8.
Clin Gastroenterol Hepatol ; 20(2): 409-418.e5, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33279780

RESUMO

BACKGROUND & AIMS: Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. METHODS: Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006-2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. RESULTS: Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. CONCLUSIONS: A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.


Assuntos
Hepatite Alcoólica , Transplante de Fígado , Abstinência de Álcool , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Hepatite Alcoólica/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Recidiva , Estudos Retrospectivos
9.
Am J Gastroenterol ; 117(12): 1990-1998, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35853462

RESUMO

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.


Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Hepatite Alcoólica , Transplante de Fígado , Humanos , Adulto , Doença Hepática Terminal/cirurgia , Hemorragia Gastrointestinal , Índice de Gravidade de Doença , Hepatite Alcoólica/cirurgia , Estudos Retrospectivos
10.
Hepatology ; 73(6): 2110-2123, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32926749

RESUMO

BACKGROUND AND AIMS: Organs from hepatitis C virus (HCV)-viremic donors have been used in HCV-uninfected recipients (D+/R-), but the optimal treatment approach has not been defined. We evaluated the kinetics of HCV infection following transplant in D+/R- kidney-transplant (KT) and liver-transplant (LT) recipients when a preemptive antiviral strategy was used. APPROACH AND RESULTS: Six US transplant programs prospectively treated D+/R- primary LT and KT recipients with sofosbuvir-velpastasvir for 12 weeks starting once viremia was confirmed following transplant and the patients were judged to be clinically stable, including estimated glomerular filtration rate >30 mL/min. Primary endpoints were sustained virologic response at 12 weeks following transplant and safety (assessed by proportion of treatment-related adverse and serious adverse events). Of the 24 patients transplanted (13 liver, of whom 2 had prior-treated HCV infection; 11 kidney), 23 became viremic after transplant. The median (interquartile range) time from transplant to start of antiviral therapy was 7.0 (6.0, 12.0) versus 16.5 (9.8, 24.5) days, and the median (interquartile range) HCV-RNA level 3 days after transplant was 6.5 (3.9, 7.1) versus 3.6 (2.9, 4.0) log10  IU/mL in LT versus KT recipients, respectively. By week 4 of treatment, 10 of 13 (77%) LT, but only 2 of 10 (20%) KT, had undetectable HCV RNA (P = 0.01). At the end of treatment, all LT recipients were HCV RNA-undetectable, whereas 3 (30%) of the kidney recipients still had detectable, but not quantifiable, viremia. All achieved sustained virologic response at 12 weeks following transplant (lower 95% confidence interval bound: 85%). Serious adverse events considered possibly related to treatment were antibody-mediated rejection, biliary sclerosis, cardiomyopathy, and graft-versus-host disease, with the latter associated with multiorgan failure, premature treatment discontinuation, and death. CONCLUSIONS: Despite differing kinetics of early HCV infection in liver versus non-liver recipients, a preemptive antiviral strategy is effective. Vigilance for adverse immunologic events is warranted.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C/prevenção & controle , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Carbamatos/administração & dosagem , Esquema de Medicação , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Rim/virologia , Modelos Lineares , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Doadores de Tecidos , Transplantados , Carga Viral/efeitos dos fármacos , Viremia
11.
Clin Transplant ; 36(10): e14647, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35303370

RESUMO

BACKGROUND: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients. OBJECTIVES: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT. SECONDARY OBJECTIVES: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as if weight loss in obese patients affects short-term outcomes after LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 RESULTS: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. CONCLUSIONS: We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.


Assuntos
Transplante de Fígado , Estado Nutricional , Humanos , Estudos Retrospectivos , Obesidade , Estudos Observacionais como Assunto
13.
Ann Surg ; 274(3): 411-418, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34132702

RESUMO

OBJECTIVE: This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT). SUMMARY BACKGROUND DATA: Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation. METHODS: Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48 hours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables. RESULTS: Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12 months post-LT, respectively, when compared to recipients with lower (<0.072) clonality. T-cell repertoire clonality was the only predictor of sepsis 3 months post-LT in multivariate analysis (C-Statistic, 0.75). Adequate treatment resulted in equivalent survival rates between both groups: (93.4% vs 96.2%, respectively, P = 0.41) at 12 months post-LT. CONCLUSIONS: T-cell repertoire clonality is a novel biomarker predictor of sepsis before development of clinical symptoms. Early sepsis monitoring and management may reduce post-LT mortality. These findings have implications for developing sepsis-prevention protocols in transplantation and potentially other populations.


Assuntos
Hematopoiese Clonal/imunologia , Transplante de Fígado , Receptores de Antígenos de Linfócitos T/imunologia , Sepse/diagnóstico , Idoso , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Sepse/imunologia
14.
J Clin Immunol ; 41(8): 1733-1744, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34570326

RESUMO

BACKGROUND: It is important to predict which patients infected by SARS-CoV-2 are at higher risk of life-threatening COVID-19. Several studies suggest that neutralizing auto-antibodies (auto-Abs) against type I interferons (IFNs) are predictive of critical COVID-19 pneumonia. OBJECTIVES: We aimed to test for auto-Abs to type I IFN and describe the main characteristics of COVID-19 patients admitted to intensive care depending on whether or not these auto-Abs are present. METHODS: Retrospective analysis of all COVID-19 patients admitted to an intensive care unit (ICU) in whom samples were available, from March 2020 to March 2021, in Barcelona, Spain. RESULTS: A total of 275 (70.5%) out of 390 patients admitted to ICU were tested for type I IFNs auto-antibodies (α2 and/or ω) by ELISA, being positive in 49 (17.8%) of them. Blocking activity of plasma diluted 1/10 for high concentrations (10 ng/mL) of IFNs was proven in 26 (9.5%) patients. Almost all the patients with neutralizing auto-Abs were men (92.3%). ICU patients with positive results for neutralizing IFNs auto-Abs did not show relevant differences in demographic, comorbidities, clinical features, and mortality, when compared with those with negative results. Nevertheless, some laboratory tests (leukocytosis, neutrophilia, thrombocytosis) related with COVID-19 severity, as well as acute kidney injury (17 [65.4%] vs. 100 [40.2%]; p = 0.013) were significantly higher in patients with auto-Abs. CONCLUSION: Auto-Abs neutralizing high concentrations of type I IFNs were found in 9.5% of patients admitted to the ICU for COVID-19 pneumonia in a hospital in Barcelona. These auto-Abs should be tested early upon diagnosis of SARS-CoV-2 infection, as they account for a significant proportion of life-threatening cases.


Assuntos
Anticorpos Neutralizantes/sangue , Autoanticorpos/sangue , COVID-19/imunologia , Interferon Tipo I/imunologia , SARS-CoV-2 , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Gastroenterology ; 157(2): 472-480.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30998988

RESUMO

BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.


Assuntos
Doença Hepática Terminal/cirurgia , Hepatite Alcoólica/cirurgia , Transplante de Fígado/métodos , Modelos Biológicos , Tempo para o Tratamento , Adulto , Abstinência de Álcool , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/prevenção & controle , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Hepatite Alcoólica/complicações , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Expectativa de Vida , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Listas de Espera
17.
Hepatology ; 69(4): 1477-1487, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30561766

RESUMO

Early liver transplant (LT) for alcohol-associated disease (i.e., without a specific sobriety period) is controversial but increasingly used. Using the multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) cohort, we aimed to develop a predictive tool to identify patients pretransplant with low risk for sustained alcohol use posttransplant to inform selection of candidates for early LT. We included consecutive ACCELERATE-AH LT recipients between 2012 and 2017. All had clinically diagnosed severe alcoholic hepatitis (AH), no prior diagnosis of liver disease or AH, and underwent LT without a specific sobriety period. Logistic and Cox regression, classification and regression trees (CARTs), and least absolute shrinkage and selection operator (LASSO) regression were used to identify variables associated with sustained alcohol use post-LT. Among 134 LT recipients for AH with median period of alcohol abstinence pre-LT of 54 days, 74% were abstinent, 16% had slips only, and 10% had sustained alcohol use after a median 1.6 (interquartile range [IQR]: 0.7-2.8) years follow-up post-LT. Four variables were associated with sustained use of alcohol post-LT, forming the Sustained Alcohol Use Post-LT (SALT) score (range: 0-11): >10 drinks per day at initial hospitalization (+4 points), multiple prior rehabilitation attempts (+4 points), prior alcohol-related legal issues (+2 points), and prior illicit substance abuse (+1 point). The C statistic was 0.76 (95% confidence interval [CI]: 0.68-0.83). A SALT score ≥5 had a 25% positive predictive value (95% CI: 10%-47%) and a SALT score of <5 had a 95% negative predictive value (95% CI: 89%-98%) for sustained alcohol use post-LT. In internal cross-validation, the average C statistic was 0.74. Conclusion: A prognostic score, the SALT score, using four objective pretransplant variables identifies candidates with AH for early LT who are at low risk for sustained alcohol use posttransplant. This tool may assist in the selection of patients with AH for early LT or in guiding risk-based interventions post-LT.


Assuntos
Consumo de Bebidas Alcoólicas , Hepatite Alcoólica/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias , Adulto , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco
18.
Proc Natl Acad Sci U S A ; 114(26): 6722-6727, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28630353

RESUMO

A number of analyses, meta-analyses, and assessments, including those performed by the Intergovernmental Panel on Climate Change, the National Oceanic and Atmospheric Administration, the National Renewable Energy Laboratory, and the International Energy Agency, have concluded that deployment of a diverse portfolio of clean energy technologies makes a transition to a low-carbon-emission energy system both more feasible and less costly than other pathways. In contrast, Jacobson et al. [Jacobson MZ, Delucchi MA, Cameron MA, Frew BA (2015) Proc Natl Acad Sci USA 112(49):15060-15065] argue that it is feasible to provide "low-cost solutions to the grid reliability problem with 100% penetration of WWS [wind, water and solar power] across all energy sectors in the continental United States between 2050 and 2055", with only electricity and hydrogen as energy carriers. In this paper, we evaluate that study and find significant shortcomings in the analysis. In particular, we point out that this work used invalid modeling tools, contained modeling errors, and made implausible and inadequately supported assumptions. Policy makers should treat with caution any visions of a rapid, reliable, and low-cost transition to entire energy systems that relies almost exclusively on wind, solar, and hydroelectric power.

19.
Am J Transplant ; 19(10): 2900-2909, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31152491

RESUMO

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.


Assuntos
Amiloidose/mortalidade , Cardiomiopatias/mortalidade , Transplante de Coração/mortalidade , Transplante de Células-Tronco/mortalidade , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Amiloidose/complicações , Amiloidose/patologia , Amiloidose/terapia , Cardiomiopatias/complicações , Cardiomiopatias/patologia , Cardiomiopatias/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento
20.
Gastroenterology ; 155(2): 422-430.e1, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29655837

RESUMO

BACKGROUND & AIMS: The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. METHODS: We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. RESULTS: Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01). CONCLUSIONS: In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.


Assuntos
Abstinência de Álcool/estatística & dados numéricos , Consumo de Bebidas Alcoólicas/epidemiologia , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Seleção de Pacientes , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/mortalidade , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
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