Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials / Factor estimulante de colonias de granulocitos en el fallo hepático agudo sobre crónico: revisión sistemática y metaanálisis de estudios aleatorizados controlados

Background and aims: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. Methods: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. Results: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. Conclusion. In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF...(AU)

Antecedentes y objetivos: La respuesta inmune disfuncional es clave en la patogénesis del fallo hepático agudo sobre crónico (ACLF). Se ha sugerido que la utilización de factor estimulante de colonias de granulocitos (G-CSF) aumenta la supervivencia de los pacientes con ACLF al mejorar la disfunción inmune y promover la regeneración hepática. El objetivo del estudio es evaluar el beneficio en supervivencia que proporciona la administración de G-CSF en comparación con el tratamiento médico estándar (SMT) en pacientes con ACLF. Métodos: Se llevó a cabo una revisión sistemática y meta-análisis de estudios aleatorizados y controlados. El objetivo principal fue analizar la supervivencia a los 60-90 días. Se realizó una búsqueda en Ovid Medline, EMBASE, y el registro central de estudios controlados de Cochrane desde su inicio hasta agosto 2021. También se realizaron búsquedas manuales en la bibliografía de artículos relevantes y presentaciones a congresos. Se utilizó la herramienta revisada de Cochrane para analizar la calidad y el riesgo de sesgos. Los datos fueron extraídos por dos investigadores independientes y las discrepancias fueron resueltas por un tercer investigador. Resultados: La búsqueda inicial identificó 142 estudios. De estos, 4 aleatorizados y controlados fueron elegidos para el análisis cuantitativo, incluyendo un total de 310 pacientes (154 G-CSF y 156 SMT). Se objetivó un alto grado de heterogeneidad entre los estudios (I2 = 74%, Chi 2 = 11.57, p = 0.009). La administración de G-CSF no aumentó la supervivencia en el grupo de pacientes con ACLF (modelo de efectos aleatorios, risk ratio = 0.64 [95% CI 0.39, 1.07]). Sin embargo, cuando se analizó el subgrupo de estudios realizados en Asia, sí se objetivó una disminución significativa de la mortalidad (risk ratio = 0.53 [95% CI 0.35, 0.81]). Las escalas de gravedad (MELD y Child) y la movilización de células CD34+ periféricas no mejoró significativamente tras la administración de G-CSF....(AU)

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. METHODS: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. RESULTS: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. CONCLUSION: In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.

Evolución de los pacientes con enfermedad hepática crítica / Prognosis of patients with critical hepatic disease

INTRODUCTION: The acute liver failure on chronic (ACLF), is an entity, whose recognition is increasing. The ACLF and CLIF OF indexes have been recently presented with the objective of predicting mortality in this kind of patients. MATERIAL AND METHODS: All patients admitted to the Ramón y Cajal University Hospital diagnosed of acute liver failure on chronic during 2016 and 2017 were collected. We collect the scores: SOFA, CLIF, APACHE II, SAPS II and ACLF score in patients admitted to the ICU by comparing them with each other and define which stages have worse prognosis. RESULTS: A total of 46 patients were collected. The study presents an intra ICU mortality of 31% (15/46) and a six-month mortality of 59.6% (28/46). Patients classified as death, present ACLF values ​​at admission (49.5 vs 60 p = 0.001), and at three days (46.66 vs 59.4 p = 0.001) higher than survivors. In the analysis of the ROC curve, the area under the curve in relation to six-month mortality is higher in the ACLF index (0.8) compared to the MELD (0.69) SOFA (0.66) SAPS II (0.69) or APACHE II (0.65). Patients with ACLF indexes above 65 had an intra UCI mortality of 54%, however, mortality at 6 months is 90%. Patients with ACLF values ​​greater than 65 present mean values ​​of lactic acid, leukocytes, INR or bilirubin higher than those under 65 in a statistically significant manner. CONCLUSIONS: The data presented in this study suggest that the ACLF index works as an adequate predictor of intra-ICU mortality and at 6 months.

INTRODUCCIÓN: El fallo hepático agudo sobre crónico es una entidad cuyo reconocimiento va en aumento. Los índices ACLF y CLIF OF, han sido presentados recientemente con el objetivo de predecir la mortalidad en este tipo de enfermos. MATERIAL Y MÉTODOS: Se recogen todos los pacientes ingresados en una unidad de cuidados intensivos (UCI) de un hospital terciario universitario, diagnosticados de fallo hepático agudo sobre crónico durante 2016 y 2017. Recogemos los índices SOFA, CLIF, APACHE II, SAPS II Y ACLF en pacientes ingresados en UCI comparándolos entre sí. Definimos que estadios presentan peor pronóstico. RESULTADOS: Se analizan un total de 46 pacientes. El estudio presenta una mortalidad intra-UCI del 31% (15/46) y una mortalidad a los seis meses de 59,6% (28/46). Los pacientes clasificados como éxitus presentan valores ACLF al ingreso (49,5 vs 60 p = 0,001), a los tres días (46,66 vs 59,4 p = 0,001) superiores a los supervivientes. En el análisis de la curva COR, el área bajo la curva en relación a la mortalidad a los seis meses, es superior en el índice ACLF (0,8) en comparación con el MELD (0,69) SOFA (0,66) SAPS II (0,69) o APACHE II (0,65). Los pacientes con índices ACLF superiores a 65 presentaban una mortalidad intra-UCI del 54% sin embargo, la mortalidad a los 6 meses es del 90%. Los pacientes con valores ACLF superiores a 65 presentan a su vez valores medios de láctico, leucocitos, INR o bilirrubina mayores de forma estadísticamente significativa. CONCLUSIONES: Los datos presentados en este estudio sugieren que el índice ACLF funciona como un adecuado predictor de mortalidad intra-UCI y a los 6 meses.