RESUMEN
BACKGROUND & AIMS: Patients with acute decompensation of cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands. METHODS: We conducted a nationwide observational cohort study, including patients with a history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier survival curves and an adjusted Cox proportional hazard model. RESULTS: Out of the 3,035 patients, 1,819 (59.9%) had ACLF-3. 1,420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71; 95% CI 0.66-0.76) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (log-rank p <0.0001). However, after adjusting for age, malignancy status and MELD score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within 1 year after hospital discharge. CONCLUSION: In this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge. IMPACT AND IMPLICATIONS: Patients with acute-on-chronic liver failure often require intensive care unit (ICU) admission for organ support. In these patients, short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of acute-on-chronic liver failure at ICU admission does not influence 1-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.
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Insuficiencia Hepática Crónica Agudizada , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Alta del Paciente , Humanos , Países Bajos/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/epidemiología , Anciano , Trasplante de Hígado/estadística & datos numéricos , Estudios de Cohortes , Adulto , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicacionesRESUMEN
No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = - 0.874, P < 0.001), AST (R = - 0.812, P = 0.004) and ALT (R = - 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.
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Citocromo P-450 CYP1A2/genética , Trasplante de Hígado/métodos , Hígado/fisiología , Preservación de Órganos/instrumentación , Perfusión/instrumentación , Adulto , Anciano , Isquemia Fría , Supervivencia de Injerto , Humanos , Ácido Láctico/metabolismo , Hígado/cirugía , Hepatopatías/patología , Donadores Vivos , Persona de Mediana Edad , Probabilidad , Prueba de Estudio Conceptual , Daño por ReperfusiónAsunto(s)
Trasplante de Hígado/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Aloinjertos/metabolismo , Animales , Femenino , Humanos , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-8/análisis , Interleucina-8/metabolismo , Hígado/metabolismo , Células Madre Mesenquimatosas/metabolismo , Modelos Animales , Comunicación Paracrina , Sus scrofa , Trasplante Heterólogo/métodosRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a frequent complication after liver transplantation. Although numerous risk factors for AKI have been identified, their cumulative impact remains unclear. Our aim was therefore to design a new model to predict post-transplant AKI. METHODS: Risk analysis was performed in patients undergoing liver transplantation in two centres (n = 1230). A model to predict severe AKI was calculated, based on weight of donor and recipient risk factors in a multivariable regression analysis according to the Framingham risk-scheme. RESULTS: Overall, 34% developed severe AKI, including 18% requiring postoperative renal replacement therapy (RRT). Five factors were identified as strongest predictors: donor and recipient BMI, DCD grafts, FFP requirements, and recipient warm ischemia time, leading to a range of 0-25 score points with an AUC of 0.70. Three risk classes were identified: low, intermediate and high-risk. Severe AKI was less frequently observed if recipients with an intermediate or high-risk were treated with a renal-sparing immunosuppression regimen (29 vs. 45%; p = 0.007). CONCLUSION: The AKI Prediction Score is a new instrument to identify recipients at risk for severe post-transplant AKI. This score is readily available at end of the transplant procedure, as a tool to timely decide on the use of kidney-sparing immunosuppression and early RRT.
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Lesión Renal Aguda/etiología , Trasplante de Hígado/efectos adversos , Medición de Riesgo , Lesión Renal Aguda/terapia , Adulto , Índice de Masa Corporal , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Plasma , Complicaciones Posoperatorias , Terapia de Reemplazo Renal , Factores de Riesgo , Sensibilidad y Especificidad , Isquemia TibiaRESUMEN
The aim of this study was to investigate the impact of hypoxia and hypotension during the agonal phase of donor warm ischemia time (DWIT) on hepatic ischemia/reperfusion injury (IRI) and complications in donation after circulatory death (DCD) liver transplantation. A retrospective single-center study of 93 DCD liver transplants (Maastricht type III) was performed. DWIT was divided into 2 periods: the agonal phase (from withdrawal of treatment [WoT] until circulatory arrest) and the asystolic phase (circulatory arrest until cold perfusion). A drop to <80% in peripheral oxygenation (SpO2 ) was considered as hypoxia in the agonal phase (SpO2 -agonal) and a drop to <50 mm Hg as hypotension in the agonal phase (SBP-agonal). Peak postoperative aspartate transaminase level >3000 U/L was considered as severe hepatic IRI. SpO2 dropped within 2 minutes after WoT <80%, whereas the systolic blood pressure dropped to <50 mm Hg after 9 minutes, resulting in a longer SpO2 -agonal (13 minutes) than SBP-agonal (6 minutes). In multiple logistic regression analysis, only duration of SpO2 -agonal was associated with severe hepatic IRI (P = 0.006) and not SBP-agonal (P = 0.32). Also, recipients with long SpO2 -agonal (>13 minutes) had more complications with a higher Comprehensive Complication Index during hospital admission (43.0 versus 32.0; P = 0.002) and 90-day graft loss (26% versus 6%; P = 0.01), compared with recipients with a short SpO2 -agonal (≤13 minutes). Furthermore, Cox proportional hazard modeling identified a long SpO2 -agonal as a risk factor for longterm graft loss (hazard ratio, 3.30; 95% confidence interval, 1.15-9.48; P = 0.03). In conclusion, the onset of hypoxia during the agonal phase is related to the severity of hepatic IRI and postoperative complications. Therefore, SpO2 <80% should be considered as the start of functional DWIT in DCD liver transplantation.
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Hepatectomía/efectos adversos , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/epidemiología , Daño por Reperfusión/etiología , Isquemia Tibia/efectos adversos , Adulto , Aloinjertos/irrigación sanguínea , Aloinjertos/patología , Selección de Donante , Femenino , Supervivencia de Injerto , Humanos , Hipotensión/complicaciones , Hipoxia/complicaciones , Hígado/irrigación sanguínea , Hígado/patología , Hígado/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Daño por Reperfusión/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation and more frequently observed when high-risk grafts, such as donation after circulatory death (DCD) grafts are used. Our aim was to investigate the impact of the ischemia periods on development of AKI in DCD liver transplantation. METHODS: We performed a 2-center retrospective study with 368 DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac arrest-start cold perfusion). We introduced a new period of warm ischemia: the combined warm ischemia time (combined WIT), which was defined as the sum of DWIT and recipient WIT. RESULTS: AKI was observed in 65% of the recipients and severe AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in recipients with the most severe form of AKI (P < 0.001). On multivariable analysis, increasing duration of the combined WIT was associated with an increased risk of developing severe AKI (odds ratio, 1.032 per every extra minute; 95% confidence interval, 1.014-1.051; P < 0.001). No relation was observed between length of cold ischemia time and severe AKI. CONCLUSIONS: Combined WIT is a newly defined period of warm ischemia in DCD liver transplantation. Length of combined WIT is associated with severity of postoperative AKI and should ideally not exceed 60 minutes.
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Lesión Renal Aguda/etiología , Trasplante de Hígado/efectos adversos , Donantes de Tejidos , Isquemia Tibia/efectos adversos , Lesión Renal Aguda/diagnóstico , Adulto , Isquemia Fría , Inglaterra , Femenino , Humanos , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Heat stroke is a life-threatening condition characterised by hyperthermia leading to multiple organ dysfunction. Acute liver failure is a rare and potentially fatal consequence of heat stroke. Management of heat stroke is mainly supportive but liver transplantation can be considered as the treatment of acute liver failure in heat stroke. However, literature on liver transplantation as a treatment for acute liver failure in heat stroke is scarce. Until now, no cases of liver transplantation for acute liver failure in non-exertional heat stroke have been reported. Here, we present the first case report of a successful liver transplantation in a patient with acute liver failure caused by non-exertional heat stroke after a sauna visit.
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Golpe de Calor/diagnóstico , Fallo Hepático Agudo/diagnóstico , Anciano , Diagnóstico Diferencial , Golpe de Calor/complicaciones , Calor , Humanos , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Masculino , Baño de Vapor/efectos adversosRESUMEN
OBJECTIVE: To test the total burden of complications in the early postoperative period after liver transplantation (LT) between donation after circulatory death (DCD) and donation after brain death (DBD) grafts with the novel Comprehensive Complication Index (CCI). BACKGROUND: LT is complex surgery and the increasing use of high-risk grafts is pressuring current postoperative outcomes. DCD grafts in particular are associated with ischemic-type biliary lesions (ITBL) with subsequent impaired graft survival rates. METHODS: Retrospective single-center study of all LT since the start of DCD program (2001-2015). CCI (at hospital discharge and after 6 months) was the result of all complications weighted by their Clavien-Dindo grade. A multiple logistic regression model was used to identify factors associated with a complex postoperative course (CCI at 6 months >60). RESULTS: In total, 441 cases were included: 115 DCD and 326 DBD grafts. Median in-hospital CCI was comparable for both groups (DCD 38.2; DBD 36.7; P = 0.429). Six-month postoperative median CCI was significantly higher for DCD grafts (53.4 vs 47.2; P = 0.041). Moreover, more DCD recipients underwent retransplantation for ITBL in this period (4% vs 1%; P = 0.031). Logistic regression identified recipient BMI (P = 0.046), recipient warm ischemia time (odds ratio, OR, 1.032; 95% CI, 1.008-1.056; P = 0.008), and DCD graft (OR 3.913; 95% CI 1.200-12.767; P = 0.024) as risk factors for a CCI >60. CONCLUSIONS: This analysis shows a comparable complication rate during the index hospital stay for DCD and DBD LT, but the CCI increases significantly for DCD recipients in 6 months after transplantation. Reduction of biliary complications, especially ITBL, is needed to improve the outcomes for DCD grafts.
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Muerte Encefálica , Selección de Donante/métodos , Trasplante de Hígado , Complicaciones Posoperatorias/etiología , Donantes de Tejidos , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Trasplante de Hígado/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/epidemiología , Estudios RetrospectivosRESUMEN
Acute kidney injury (AKI) is a common postoperative complication after liver transplantation (LT). The occurrence of postoperative AKI after LT (Post-LT AKI) is associated with inferior patient and graft outcomes. Post-LT AKI is multifactorial in origin and has been related to the severity of liver disease, pre-LT renal dysfunction, graft quality, perioperative events and toxicity of immunosuppressive therapy. Furthermore it is thought that hepatic ischaemia reperfusion injury might be a driving force in the aetiology of post-LT AKI. Novel biomarkers for AKI are emerging and can be useful for early identification and characterization of AKI. There is a clear need for strategies aimed at preventing or treating post-LT AKI. Several pharmacological and non-pharmacological interventions have been studied, but so far failed to show any benefit in the prevention of post-LT AKI. Further studies are needed to develop and evaluate new interventions aimed at preventing post-LT AKI and improve patient outcomes.
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Lesión Renal Aguda/etiología , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Lesión Renal Aguda/patología , Femenino , Humanos , Hepatopatías/patología , Masculino , Factores de RiesgoRESUMEN
Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.
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Lesión Renal Aguda/etiología , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Daño por Reperfusión/etiología , Lesión Renal Aguda/fisiopatología , Adulto , Aspartato Aminotransferasas/sangre , Presión Sanguínea , Muerte Encefálica , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Daño por Reperfusión/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Síndrome , Donantes de TejidosRESUMEN
miRNAs have emerged as promising biomarkers because of their association with cell stress and diseases and their easy detection and stability in many body fluids. Because of the sensitivity, the method of choice to detect miRNAs is quantitative RT-PCR (RT-qPCR). Therapeutics, in particular circulating anticoagulants, are notorious for their inhibitory effect on RT-qPCR-based measurements. The effect of heparin contamination on inhibition of RT-qPCR from miRNAs isolated from urine has, however, never been investigated. We obtained urine samples from healthy controls and from heparinized patients undergoing major surgery (live kidney donation or liver transplantation) (n = 27). Samples were spiked with synthetic miRNAs to monitor RNA loss during workup, and levels of endogenous and spiked-in miRNAs were quantified by RT-qPCR. Endogenous miRNAs in urine were protected from degradation, but levels differed substantially within surgery groups. Variability in detection levels of spiked-in miRNAs was low in nonhospitalized controls, but was high in both surgery groups, and the difference in miRNA levels correlated well with the heparin concentration in urinary samples. Treatment of urinary RNA with heparinase I during RT-qPCR strongly reduced this variation in a dose-dependent manner. Heparinase I should therefore be considered as standard step for detection of miRNA in urine from hospitalized individuals.