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1.
Artigo em Inglês | MEDLINE | ID: mdl-38969073

RESUMO

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS: The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

2.
Liver Transpl ; 30(2): 192-199, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146168

RESUMO

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.


Assuntos
Metabolismo Energético , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Aumento de Peso , Obesidade , Ácidos Graxos
3.
Dig Dis Sci ; 69(5): 1844-1851, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499735

RESUMO

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.


Assuntos
Algoritmos , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Transplante de Fígado , Vibração , Humanos , Técnicas de Imagem por Elasticidade/métodos , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Feminino , Masculino , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Adulto , Biópsia , Idoso , Fígado/patologia , Fígado/diagnóstico por imagem , Estudos Retrospectivos
4.
Clin Gastroenterol Hepatol ; 21(4): 1100-1102.e2, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35181567

RESUMO

Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.


Assuntos
Regras de Decisão Clínica , Técnicas de Imagem por Elasticidade , Transplante de Fígado , Transplantados , Vibração , Fígado/patologia , Modelos Estatísticos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso
5.
Liver Transpl ; 29(2): 196-205, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36036790

RESUMO

Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.


Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Fibrose , Curva ROC , Técnicas de Imagem por Elasticidade/métodos , Biópsia
6.
Liver Transpl ; : 196-205, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37160063

RESUMO

ABSTRACT: Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n  = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.

7.
Liver Int ; 42(6): 1401-1409, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35129295

RESUMO

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Carboidratos , Humanos , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações
8.
Environ Geochem Health ; 42(11): 3753-3764, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32583130

RESUMO

Rice production in floodplain deltas is currently vulnerable to climate change and contamination from anthropogenic activities. The relocation of rice production to upland regions could be an option for increasing the sustainability of rice production. Our study evaluated the spatial patterning of heavy metals, i.e., copper (Cu) and cadmium (Cd), in rice along a topogradient from terrace to lowland areas in the Red River basin. The dataset obtained from the analysis of 61 farm sites throughout the whole basin indicated a large discrepancy in the Cu and Cd contents in rice grains from terrace and lowland paddies. While Cu and Cd were not found in most of the rice grain samples from the terrace paddies, the median Cu and Cd contents of the lowland paddy rice were 1.895 and 0.033 mg kg-1, respectively. Assessing the relationship of Cu and Cd in the soil-rice system to soil properties revealed possible correlations between soil available silicon (Si) and the Cu and Cd contents in rice grain. The enrichment of Si in rice plants likely reduces the translocation of Cu and Cd from soil to grain. Therefore, management of the Si supply, particularly in lowland paddies, should be highlighted as a way to reduce dietary intake of Cu and Cd.


Assuntos
Cádmio/análise , Cobre/análise , Oryza/química , Silício/farmacocinética , Poluentes do Solo/análise , Disponibilidade Biológica , Cádmio/farmacocinética , Cobre/farmacocinética , Contaminação de Alimentos/análise , Sementes/química , Silício/análise , Solo/química , Poluentes do Solo/farmacocinética , Vietnã
9.
Environ Monit Assess ; 188(9): 525, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27542667

RESUMO

The effect of environmental pollution on the safety of vegetable crops is a serious global public health issue. This study was conducted to assess heavy metal concentrations in soil, irrigation water, and 21 local vegetable species collected from four sites near mining activities and one control site in Northern Vietnam. Soils from vegetable fields in the mining areas were contaminated with cadmium (Cd), lead (Pb), and arsenic (As), while irrigation water was contaminated with Pb. Average concentrations of Pb and As in fresh vegetable samples collected at the four mining sites exceeded maximum levels (MLs) set by international food standards for Pb (70.6 % of vegetable samples) and As (44.1 % of vegetable samples), while average Cd concentrations in vegetables at all sites were below the MLs of 0.2. The average total target hazard quotient (TTHQ) across all vegetable species sampled was higher than the safety threshold of 1.0, indicating a health risk. Based on the weight of evidence, we find that cultivation of vegetables in the studied mining sites is an important risk contributor for local residents' health.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Mineração , Poluentes do Solo/análise , Verduras/química , Poluentes Químicos da Água/análise , Irrigação Agrícola , Arsênio/análise , Arsênio/metabolismo , Cádmio/análise , Cádmio/metabolismo , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Contaminação de Alimentos/análise , Chumbo/análise , Chumbo/metabolismo , Metais Pesados/metabolismo , Medição de Risco , Solo/química , Poluentes do Solo/metabolismo , Verduras/crescimento & desenvolvimento , Verduras/metabolismo , Vietnã , Poluentes Químicos da Água/metabolismo
10.
Neuron ; 100(4): 816-830.e7, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30344044

RESUMO

Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and to inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. VIDEO ABSTRACT.


Assuntos
Esclerose Lateral Amiotrófica/genética , Axônios/fisiologia , Demência Frontotemporal/genética , Mutação com Perda de Função/genética , Biossíntese de Proteínas/fisiologia , Proteína FUS de Ligação a RNA/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Axônios/patologia , Células Cultivadas , Feminino , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Proteína FUS de Ligação a RNA/biossíntese
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