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1.
Hepatology ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255519

RESUMEN

BACKGROUND AND AIMS: While transjugular intrahepatic portosystemic shunt (TIPS) is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes. APPROACH AND RESULTS: Adult TIPS recipients in the multicenter Advancing Liver Therapeutic Approaches retrospective cohort study were included (N=1,127 patients; 2,040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at time of procedure and at 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (sHR of death 1.1 [p=0.42], 1.3 [p=0.04], and 1.7 [p<0.01] for MELD-Na 15-19, 20-24, and ≥25 relative to MELD-Na <15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6 mo) post-TIPS TFS, rates of long-term TFS were 88% at 1-year and 57% at 3-years post-TIPS. Additionally, a within-individual increase in MELD-Na score of >3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (sHR of death 1.8, p<0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low. CONCLUSIONS: Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by post-procedure changes in MELD-Na and clinical status. For selected patients, "destination TIPS" without LT may offer long-term survival with freedom from portal hypertensive complications.

2.
Hepatology ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39325984

RESUMEN

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) is associated with very high mortality despite abstinence from alcohol; up to 40% of patients die within 6 months of diagnosis. Patients with AH are especially prone to infections, which can lead to multiorgan dysfunction and poorer prognosis. APPROACH AND RESULTS: We performed comprehensive serological profiling of the viral and bacterial infection history of 36 healthy controls, 48 patients with alcohol use disorder, and 224 patients with AH from 2 multicenter observational studies. We used systematic viral and bacterial epitope scanning by VirScan, a phage-display immunoprecipitation and sequencing technology that detects the peptides recognized by antibodies in patient sera, to comprehensively analyze antiviral and antibacterial antibodies and identify serologic biomarkers to predict patient outcomes. We found significant differences in the serological profiles of the 3 populations. The number of serum antibody epitopes in patients with alcohol use disorder during abstinence was increased compared with during active alcohol use. A decreased number and diversity of viral and bacterial antibody targets were detected in the sera of patients with AH, particularly those with a higher Child-Pugh score. In patients with AH, a decrease in the serum antiviral, but not antibacterial, antibody repertoire was associated with decompensation and mortality. Ninety-day mortality in AH could be predicted using a serum viral epitope signature. CONCLUSIONS: Abstinence from alcohol is associated with a significant increase in serum viral and bacterial antibody response. Decreased serum antiviral antibody repertoire is predictive of decompensation of liver disease and mortality in patients with AH.

4.
Hepatol Commun ; 8(8)2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39082963

RESUMEN

BACKGROUND: Alcohol-associated hepatitis (AH) is associated with significant mortality. Model for End-Stage Liver Disease (MELD) score is used to predict short-term mortality and aid in treatment decisions. MELD is frequently updated in the course of AH. However, once the most updated MELD is known, it is uncertain if previous ones still have prognostic value, which might be relevant for transplant allocation and trial design. We aimed to investigate the predictive performance of updated MELDs in a prospectively collected cohort of patients with AH by the InTeam consortium. METHODS: Three hundred seven patients (with 859 MELD values within 60 d of admission) fulfilled the inclusion criteria. The main endpoint was time to death or transplant up to 90 days. We used a joint model approach to assess the predictive value of updated MELDs. RESULTS: Updated MELD measurements had a strong prognostic value for death/transplant (HR: 1.20, 95% CI: 1.14-1.27) (p < 0.0001). Previous MELD values did not add predictive value to the most current MELD. We also showed that MELD at day 28 (MELD28) had a significant predictive value for subsequent mortality/transplant in a landmark analysis (HR: 1.18, 95% CI: 1.12-1.23). We show that the use of an ordinal scale including death, transplant, and MELD28 as a trial outcome could substantially reduce the sample size required to demonstrate short-term benefit of an intervention. CONCLUSION: We show that updated MELDs during the trajectory of AH predict subsequent mortality or the need for transplant. MELD28 inclusion in an ordinal outcome (together with death or transplant) could increase the efficiency of randomized controlled trials.


Asunto(s)
Hepatitis Alcohólica , Trasplante de Hígado , Índice de Severidad de la Enfermedad , Humanos , Hepatitis Alcohólica/mortalidad , Hepatitis Alcohólica/tratamiento farmacológico , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Valor Predictivo de las Pruebas
5.
Gut ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033024

RESUMEN

OBJECTIVE: Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils. DESIGN: In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet). RESULT: Faecal proteomic profiles were overall significantly different between controls, patients with AUD and AH (principal component analysis p=0.001, dissimilarity index calculated by the method of Bray-Curtis). Proteins that showed notable differences across all three groups and displayed a progressive increase in accordance with the severity of alcohol-associated liver disease were predominantly those located in neutrophil granules. Over-representation and Reactome analyses confirmed that differentially regulated proteins are part of granules in neutrophils and the neutrophil degranulation pathway. Myeloperoxidase (MPO), the marker protein of neutrophil granules, correlates with disease severity and predicts 60-day mortality. Using an independent validation cohort, we confirmed that faecal MPO levels can predict short-term survival at 60 days. CONCLUSIONS: We found an increased abundance of faecal proteins linked to neutrophil degranulation in patients with AH, which is predictive of short-term survival and could serve as a prognostic non-invasive marker.

6.
Am J Gastroenterol ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018024

RESUMEN

INTRODUCTION: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. METHODS: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. RESULTS: The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified. DISCUSSION: The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion. REGISTRATION: NCT05740358.

7.
Liver Transpl ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39041923

RESUMEN

Among patients with decompensated cirrhosis, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We found that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCr diff ) would quantify this bias and be independently associated with outcomes. We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCr diff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCr diff , divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCr diff and waitlist mortality. In Cox regression, cysC was significantly more associated with waitlist mortality than sCr ( p < 0.001). We found that as compared to those with a low cysCsCr diff , those with an intermediate or high cysCsCr diff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores ( p < 0.05 for all). Compared to those with a low cysCsCr diff , we found that those in the intermediate and high groups were more likely to die during follow-up (low: 6% vs. intermediate: 8% vs. high: 11%, p = 0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCr diff was associated with 1.72× (1.27-2.32) the hazard of waitlist mortality. Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCr diff represents a novel independent metric associated with waitlist mortality.

8.
Hepatology ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39047086

RESUMEN

BACKGROUND AND AIMS: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify the net survival benefit with LT by liver frailty index (LFI). APPROACH AND RESULTS: We analyzed data in the multicenter Functional Assessment in LT (FrAILT) study from 2012 to 2021. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without HCC; the post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. We computed 1-, 3-, and 5-year restricted mean survival times (RMSTs) from adjusted Cox models. The survival benefit was calculated as a net gain in life-years with LT. Pre-LT cohort included 2628 patients: median Model for End-Stage Liver Disease-Sodium was 18 (IQR: 14-22); 731 (28%) were frail; 440 (17%) died before LT. Post-LT cohort included 1335 patients: median Model for End-Stage Liver Disease-Sodium was 20 (IQR: 14-24); 325 (24%) were frail; 103 (8%) died after LT. Pre-LT RMST decreased substantially as LFI increased. Post-LT RMST also decreased as LFI increased but only modestly. There was no LFI threshold at which pre-LT and post-LT RMST intersected-patients had net survival benefits at all LFI values. CONCLUSIONS: Pre-LT and, to a lesser degree, post-LT mortality increased as LFI increased. Transplant offered a survival benefit at all LFI values, driven by a reduction in pre-LT mortality. No threshold of LFI was identified at which the risk of post-LT mortality exceeded pre-LT mortality. LT offers net survival benefits even in the presence of advanced frailty among those selected for LT.

10.
Nat Rev Gastroenterol Hepatol ; 21(9): 626-645, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38849555

RESUMEN

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.


Asunto(s)
Consumo de Bebidas Alcohólicas , Ensayos Clínicos como Asunto , Hepatopatías Alcohólicas , Humanos , Hepatopatías Alcohólicas/terapia , Consumo de Bebidas Alcohólicas/efectos adversos , Consenso , Proyectos de Investigación , Alcoholismo/complicaciones , Alcoholismo/terapia
11.
Liver Transpl ; 30(10): 991-1001, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38900010

RESUMEN

Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI), which is potentially modifiable. We aimed to identify LFI cut-points associated with waitlist mortality. Ambulatory adults with cirrhosis without HCC awaiting liver transplantation from 9 centers from 2012 to 2021 for ≥3 months with ≥2 pre-liver transplantation LFI assessments were included. The primary explanatory variable was the change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick), with transplant considered as a competing event. Among 1029 patients, the median (IQR) age was 58 (51-63) years; 42% were female; and the median lab Model for End-Stage Liver Disease-Sodium at first assessment was 18 (15-22). For each 0.1 improvement in ∆LFI, the risk of overall mortality decreased by 6% (cause-specific hazard ratio: 0.94, 95% CI: 0.92-0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cause-specific hazard ratio: 0.63, 95% CI: 0.46-0.87) and 0.2 (HR: 0.61, 95% CI: 0.42-0.87). An improvement in LFI per 3 months as small as 0.1 in the pre-liver transplantation period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess the effectiveness of interventions targeting physical frailty in patients with cirrhosis.


Asunto(s)
Fragilidad , Cirrosis Hepática , Trasplante de Hígado , Listas de Espera , Humanos , Listas de Espera/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Fragilidad/diagnóstico , Fragilidad/mortalidad , Fragilidad/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/complicaciones , Factores de Riesgo , Índice de Severidad de la Enfermedad , Medición de Riesgo/estadística & datos numéricos , Medición de Riesgo/métodos , Estudios Retrospectivos , Hígado/cirugía
12.
Transplantation ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771067

RESUMEN

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

13.
Hepatol Commun ; 8(5)2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38696374

RESUMEN

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.


Asunto(s)
Continuidad de la Atención al Paciente , Disparidades en Atención de Salud , Hepatopatías , Humanos , Hepatopatías/terapia , Enfermedad Crónica , Trasplante de Hígado , Equidad en Salud , Accesibilidad a los Servicios de Salud , Cirrosis Hepática/terapia
14.
Res Sq ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38765962

RESUMEN

A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.

15.
Transplantation ; 108(10): 2100-2108, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38622762

RESUMEN

BACKGROUND: Although post liver transplant survival rates have significantly improved during the past 2-3 decades, the trend in intention-to-treat (ITT) survival (survival from waitlist addition) has not been well studied. METHODS: We conducted a retrospective analysis of Scientific Registry of Transplant Recipients data to determine the trend in ITT survival in liver transplant candidates. Adult (age ≧ 18 y) patients who were on the waitlist between the time period of March 1, 2002, to December 31, 2019 (n = 200 816) and deceased liver donors that were registered between the same time period (n = 152 593) were analyzed. RESULTS: We found a constant increase in posttransplant survival rates; however, the ITT survival rates showed no statistically significant improvement through the study period. We observed significant linear increase in waitlist dropout rates over time. We also observed linear increase in liver nonutilization rate in both entire cases and brain-dead cases. Donor risk index increased significantly over the years; however, it was mostly driven by increase in donation after circulatory death cases; without donation after circulatory death cases, donor risk index was stable throughout the 17 y we observed. CONCLUSIONS: The reason of the increased liver nonutilization rate is unclear; however, it is possible that reluctance to use high-risk organ to maintain better posttransplant outcomes contributed to this increase, which also could have led to increase in waitlist dropout rates and no improvements in ITT survival. Further investigation is warranted on the increased nonutilization rates to improve over all contribution of liver transplant to patient care.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Análisis de Intención de Tratar , Trasplante de Hígado , Sistema de Registros , Listas de Espera , Humanos , Trasplante de Hígado/mortalidad , Trasplante de Hígado/tendencias , Estudios Retrospectivos , Listas de Espera/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/diagnóstico , Donantes de Tejidos/provisión & distribución , Donantes de Tejidos/estadística & datos numéricos , Resultado del Tratamiento , Factores de Tiempo , Factores de Riesgo , Medición de Riesgo , Anciano , Obtención de Tejidos y Órganos/tendencias , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Tasa de Supervivencia/tendencias , Selección de Donante/tendencias , Supervivencia de Injerto
16.
J Hepatol ; 81(1): 163-183, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38527522

RESUMEN

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.


Asunto(s)
Lesión Renal Aguda , Síndrome Hepatorrenal , Cirrosis Hepática , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Cirrosis Hepática/complicaciones , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/diagnóstico , Ascitis/etiología , Ascitis/terapia , Ascitis/diagnóstico , Consenso
17.
Hepatology ; 80(2): 403-417, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-38377466

RESUMEN

BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group. CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.


Asunto(s)
Hepatitis Alcohólica , Receptores de Hidrocarburo de Aril , Humanos , Receptores de Hidrocarburo de Aril/sangre , Receptores de Hidrocarburo de Aril/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Hepatitis Alcohólica/mortalidad , Hepatitis Alcohólica/sangre , Adulto , Estudios de Casos y Controles , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Tasa de Supervivencia , Células Hep G2 , Anciano , Biomarcadores/sangre
18.
Eur J Gastroenterol Hepatol ; 36(3): 318-325, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38179871

RESUMEN

BACKGROUND AND AIMS: Patients with alcohol use disorder (AUD) can develop alcohol-associated fatty liver disease (AFLD). However, the impact of AFLD on outcomes remains unclear. We studied the impact of AFLD on readmission, 30-day mortality, and overall mortality in patients admitted with AUD. METHODS: Hospitalized patients with AUD between 2011 and 2019 at a tertiary medical center were retrospectively evaluated. Our population included patients with AUD with AFLD: AST and ALT elevation and serum bilirubin <3 mg/dl. Patients with AUD without evidence of liver disease served as control and were labeled as no ALD. Patients with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) were included for comparison. Kaplan-Meier survival analysis and multivariable regression for predictors of mortality and survival were performed. RESULTS: There were 7522 patients of which 32.44% were female with mean age of 51.86 ±â€…14.41 years. Patient distribution included no ALD (n = 3775), AFLD (n = 2192), AC (n = 1017) and AH (n = 538) groups. Compared to no ALD group, AFLD group was associated with significantly higher 30-day mortality [4.43% vs. 1.56%, hazard ratio (HR): 2.84; P  < 0.001], overall mortality [15.97% vs. 12.69%, HR 1.40, P  < 0.001], and 30-day readmission [21.85% vs. 18.49%, odds ratio: 1.21; P  < 0.01]. CONCLUSION: We demonstrated that AFLD is not a benign entity and poses significant mortality risk. Our results suggest that AFLD may be under-recognized and highlight the need for focused management and close follow-up after discharge.


Asunto(s)
Alcoholismo , Hígado Graso Alcohólico , Hepatitis Alcohólica , Hepatopatías Alcohólicas , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Readmisión del Paciente , Estudios Retrospectivos , Hepatopatías Alcohólicas/complicaciones , Hígado Graso Alcohólico/complicaciones , Cirrosis Hepática Alcohólica/diagnóstico , Cirrosis Hepática Alcohólica/complicaciones , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Hepatitis Alcohólica/complicaciones
19.
Am J Transplant ; 24(3): 468-478, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37871798

RESUMEN

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.


Asunto(s)
Hepatitis C , Ácidos Nucleicos , Trasplante de Órganos , Humanos , Hepacivirus/genética , Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico
20.
Clin Transplant ; 38(1): e15205, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38041450

RESUMEN

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.


Asunto(s)
Trasplante de Hígado , Trombosis de la Vena , Humanos , Índice de Masa Corporal , Trasplante de Hígado/efectos adversos , Obesidad/etiología , Complicaciones Posoperatorias/etiología , Trombosis de la Vena/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Riesgo
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