Quality of Tissue Samples Obtained by Endoscopic Ultrasound-Guided Liver Biopsy: A Randomized, Controlled Clinical Trial.

INTRODUCTION: Liver biopsy (LB) remains essential for the diagnosis and staging of parenchymal liver diseases. Endoscopic ultrasound-guided LB (EUS-LB) has emerged as an attractive alternative to percutaneous and transjugular routes. We aimed at comparing the adequacy of samples obtained by EUS-LB with percutaneous LB. METHODS: A single-center, randomized, controlled clinical trial was designed. Patients undergoing LB were randomly assigned to EUS-LB or percutaneous LB groups. EUS-LB was performed with a 19-gauge Franseen core needle through a transduodenal and transgastric route. Percutaneous LB was performed with a 16-gauge Tru-Cut needle. The main outcome was the percentage of adequate samples obtained. Secondary outcomes were the percentage of accurate histologic diagnosis, number of complete portal tracts (CPT), total and longest specimen length (TSL and LSL), sample fragmentation, adverse events, and patients' satisfaction. An adequate specimen was defined as TSL ≥20 mm and including ≥11 CPT. RESULTS: Ninety patients were randomized (44 to EUS-LB and 46 to percutaneous LB) and included in the analysis. The percentage of adequate tissue samples was 32.6% and 70.4% for percutaneous LB and EUS-LB, respectively ( P < 0.001). A final histologic diagnosis was provided in all cases but one. TSL was longer after EUS-LB (23.5 vs 17.5 mm, P = 0.01), whereas the number of CPT was similar in both groups. Sample fragmentation occurred more often after EUS-LB ( P < 0.001). No differences in adverse events were found. Satisfaction reported with both procedures was high. DISCUSSION: EUS-LB is safe and accurate and may be considered an alternative to percutaneous LB for the evaluation of parenchymal liver diseases.

Recomendaciones de uso de everolimus en el trasplante hepático / Recommendations of everolimus use in liver transplant

Los fármacos inhibidores de la mTOR, everolimus (EVL) y sirolimus, son inmunosupresores con muy poco efecto nefrotóxico, limitado al desarrollo de proteinuria en algunos casos. En la prevención del rechazo agudo EVL combinado con tacrolimus a dosis reducidas tiene una eficacia y seguridad comparables a la inmunosupresión estándar con tacrolimus. La aplicación temprana de una inmunosupresión basada en EVL con minimización de la exposición al inmunosupresor calcineurínico en trasplantados hepáticos permite mejorar los resultados de la función renal, con tasas similares de eficacia y seguridad, tanto en el período de novo como de mantenimiento. En pacientes con disfunción renal establecida la introducción de EVL permite minimizar la exposición al inmunosupresor calcineurínico, con la consiguiente mejoría en la función renal. Aunque no hay evidencia suficiente para recomendar su uso para prevenir la recurrencia del hepatocarcinoma y la progresión de tumores de novo, es práctica clínica habitual utilizarlos en este contexto (AU)

Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice (AU)

The ART-SCORE is not an effective tool for optimizing patient selection for DEB-TACE retreatment. A multicentre Spanish study / El ART-SCORE no es una herramienta eficaz para optimizar la selección de pacientes para el tratamiento con DEB-TACE. Estudio multicéntrico español

Introduction: The appropriate selection of hepatocellular carcinoma (HCC) patients who are eligible for transarterial chemoembolization (TACE) remains a challenge. The ART score has recently been proposed as a method of identifying patients who are eligible or not for a second TACE procedure. Objective: To assess the validity of the Assessment for Retreatment with TACE (ART) score in a cohort of patients treated with drug-eluting bead TACE (DEB-TACE). Secondary objective: to identify clinical determinants associated with overall survival (OS). Method: A retrospective, multicentre study conducted in Spain in patients with HCC having undergone two or more DEB-TACE procedures between January 2009 and December 2014. The clinical characteristics and OS from the day before the second DEB-TACE of patients with a high ART score (ART≥2.5) and a low ART score (ART 0-1) were compared. Risk factors for mortality were identified using Cox's proportional hazards model. Results: Of the 102 patients included, 51 scored 0-1.5 and 51 scored ≥2.5. Hepatitis C was more frequent in patients scoring ≥2.5. Median OS from the day before the second DEB-TACE was 21 months (95% CI, 15-28) in the group scoring 0-1.5, and 17 months (95% CI, 10-25) in the group scoring ≥2.5 (P=0.3562). Platelet count and tumour size, but not the ART score, were independent baseline predictors of OS. Conclusions: The ART score is not suitable for guiding DEB-TACE retreatment according to Spanish clinical practice standards (AU)

Introducción: La selección de los candidatos ideales con carcinoma hepatocelular (CHC) que más se benefician de realizar quimioembolización transarterial (TACE) sigue siendo un reto. Recientemente se ha propuesto el índice ART para seleccionar a aquellos pacientes tributarios o no de realizar un segundo procedimiento de TACE. Objetivo: Evaluar la validez del índice ART en una cohorte tratada con TACE con partículas cargadas (DEB-TACE). Objetivo secundario: identificar los factores clínicos asociados con la supervivencia global. Método: Estudio retrospectivo multicéntrico español en pacientes con CHC tratados con≥2 DEB-TACE entre enero del 2009 y diciembre del 2014. Se compararon las características clínicas y la supervivencia global desde el día previo a la segunda DEB-TACE entre los pacientes con ART alto (ART≥2,5) y bajo (ART 0-1). Los factores de riesgo de mortalidad se identificaron usando el modelo de riesgos proporcionales de Cox. Resultados: De los 102 pacientes incluidos, 51 obtuvieron puntuación de 0-1,5 y 51 ≥ 2,5. La hepatitis C fue más frecuente en pacientes con puntuación ≥ 2,5. La supervivencia global mediana desde el día previo a DEB-TACE-2 fue de 21 meses (IC del 95%, 15-28) y de 17 meses (IC del 95%, 10-25) en los pacientes con ART 0-1,5 y ≥ 2,5, respectivamente (p=0,3562). Los factores basales predictores independientes de supervivencia fueron el recuento de plaquetas y el tamaño del tumor, pero no el índice ART. Conclusiones: El índice ART no es adecuado para guiar el retratamiento con DEB-TACE según los estándares de práctica clínica español (AU)

Recommendations of everolimus use in liver transplant. / Recomendaciones de uso de everolimus en el trasplante hepático.

Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice.

The ART-SCORE is not an effective tool for optimizing patient selection for DEB-TACE retreatment. A multicentre Spanish study.

INTRODUCTION: The appropriate selection of hepatocellular carcinoma (HCC) patients who are eligible for transarterial chemoembolization (TACE) remains a challenge. The ART score has recently been proposed as a method of identifying patients who are eligible or not for a second TACE procedure. OBJECTIVE: To assess the validity of the Assessment for Retreatment with TACE (ART) score in a cohort of patients treated with drug-eluting bead TACE (DEB-TACE). SECONDARY OBJECTIVE: to identify clinical determinants associated with overall survival (OS). METHOD: A retrospective, multicentre study conducted in Spain in patients with HCC having undergone two or more DEB-TACE procedures between January 2009 and December 2014. The clinical characteristics and OS from the day before the second DEB-TACE of patients with a high ART score (ART≥2.5) and a low ART score (ART 0-1) were compared. Risk factors for mortality were identified using Cox's proportional hazards model. RESULTS: Of the 102 patients included, 51 scored 0-1.5 and 51 scored ≥2.5. Hepatitis C was more frequent in patients scoring ≥2.5. Median OS from the day before the second DEB-TACE was 21 months (95% CI, 15-28) in the group scoring 0-1.5, and 17 months (95% CI, 10-25) in the group scoring ≥2.5 (P=0.3562). Platelet count and tumour size, but not the ART score, were independent baseline predictors of OS. CONCLUSIONS: The ART score is not suitable for guiding DEB-TACE retreatment according to Spanish clinical practice standards.

Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España / Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain

INTRODUCCIÓN: GIDEON es un estudio internacional prospectivo, no intervencionista, que evaluó la seguridad de sorafenib en pacientes con carcinoma hepatocelular (CHC) no resecable en la práctica clínica diaria, incluidos pacientes Child-Pugh B. OBJETIVOS: Análisis de datos recogidos en España sobre seguridad y efectividad de sorafenib y los patrones de tratamiento. Métodos Se recogieron los datos demográficos y de la enfermedad, la dosis inicial usada, los acontecimientos adversos emergentes del tratamiento (AA) y las modificaciones de dosis a lo largo del seguimiento. Se valoraron la supervivencia global y el tiempo hasta la progresión de la enfermedad. La eficacia y la seguridad se analizaron en función de la clasificación Child-Pugh y la dosis inicial. RESULTADOS: Se incluyó a 143 pacientes de 19 hospitales españoles. El 24,5% eran pacientes Child-Pugh B. El 90,9% de los pacientes recibió una dosis inicial de 400 mg/12 h. En pacientes Child-Pugh A se modificó más frecuentemente la dosis y la duración del tratamiento fue más larga. La incidencia de AA y de aquellos relacionados con el fármaco fue similar en los pacientes Child-Pugh A y B, aunque los AA graves fueron más frecuentes en los pacientes Child-Pugh B. Los más frecuentes fueron diarrea, fatiga y eritrodisestesia palmo-plantar. La mediana de supervivencia global fue de 384 días, y superior en pacientes Child-Pugh A (593 vs. 211 días en Child-Pugh B); la mediana hasta la progresión de la enfermedad fue de 177 días, similar en ambos subgrupos. CONCLUSIÓN: El perfil de seguridad de sorafenib en pacientes españoles con CHC no resecable es independiente de la función hepática. El estado Child-Pugh no parece influir en el enfoque de dosificación de sorafenib ni en el tiempo hasta la progresión, pero sí parece ser un fuerte predictor de la supervivencia

INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. Methods Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival

[Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain]. / Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España.

INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS: Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.

Comienzo de hepatitis aguda grave autoinmune refractaria a tratamiento convencional, rescatada con infliximab / Onset of severe acute autoimmune hepatitis refractory to conventional treatment, rescued with infliximab

No disponible

[Strategies for preventing de novo hepatitis B infection after liver transplantation (II)]. / Estrategias para evitar la hepatitis B de novo postrasplante hepático (II).

Although active immunization against the hepatitis B virus (HBV) through vaccination constitutes a fundamental strategy in the prevention of infection by this virus, it is not effective in isolation for preventing de novo HBV infections in recipients of liver grafts from core antigen antibody (anti-HBc) positive donors. In this situation, the risk of developing de novo hepatitis B depends on the recipient's serological status. It has been shown that, for vaccinated patients and in the absence of prophylaxis with nucleoside/nucleotide analogues and/or hyperimmune gamma globulin, the prevalence and cumulative incidence of HBV infection after transplantation is an intermediate risk. The absence of a surface antigen antibody (anti-HBs) titer cutoff considered protective, the gradual reduction of these titers after vaccination, the presence of false positives for anti-HBs in patients undergoing infusion of blood products and escape mutations of the hepatitis B surface antigen (HBsAg) could explain this lack of efficacy. For this reason, it is recommended that vaccination protocols be implemented universally, along with the follow-up of the level of protection in patients with cirrhosis, adding prophylaxis with analogues when receiving a graft from an anti-HBc-positive donor. Clinical and serological surveillance alone can be considered for patients with anti-HBs levels greater than 200 mUI/mL after vaccination.

Estrategias para evitar la hepatitis B de novo postrasplante hepático (II) / Strategies for preventing de novo hepatitis B infection after liver transplantation (II)

Aunque la inmunización activa frente al virus de la hepatitis B (VHB) mediante la vacunación constituye una estrategia fundamental en la prevención de la infección por este virus, no resulta eficaz, de forma aislada, para la prevención de la infección por VHB de novo en receptores de un injerto hepático proveniente de un donante con positividad para el anticuerpo contra el antígeno del core (anti-HBc). En esta situación, el riesgo de desarrollar hepatitis B de novo depende del estatus serológico del receptor, y se ha comprobado que en vacunados, y en ausencia de profilaxis con análogos de nucleót(s) idos y/o gammaglobulina hiperinmune, la prevalencia y la incidencia acumuladas de la infección por VHB postrasplante los sitúan en una posición de riesgo intermedio. La ausencia de un punto de corte de títulos de anticuerpos contra el antígeno de superficie (anti-HBs) considerado protector, la disminución paulatina de estos títulos tras la vacunación, la presencia de falsos positivos para anti-HBs en sujetos sometidos a infusión de hemoderivados y mutaciones de escape del antígeno de superficie de la hepatitis B (HBsAg) podrían explicar esta ausencia de eficacia. Por este motivo, se recomienda la aplicación universal de los protocolos de vacunación y seguimiento del nivel de protección en los pacientes cirróticos, añadiendo profilaxis con análogos en caso de recibir un injerto proveniente de un donante anti-HBc positivo, y pudiendo considerarse únicamente vigilancia clínica y serológica en aquellos sujetos con niveles de anti-HBs superiores a 200 mUI/ml tras la vacunación

Although active immunization against the hepatitis B virus (HBV) through vaccination constitutes a fundamental strategy in the prevention of infection by this virus, it is not effective in isolation for preventing de novo HBV infections in recipients of liver grafts from core antigen antibody (anti-HBc) positive donors. In this situation, the risk of developing de novo hepatitis B depends on the recipient’s serological status. It has been shown that, for vaccinated patients and in the absence of prophylaxis with nucleoside/nucleotide analogues and/or hyperimmune gamma globulin, the prevalence and cumulative incidence of HBV infection after transplantation is an intermediate risk. The absence of a surface antigen antibody (anti-HBs) titer cutoff considered protective, the gradual reduction of these titers after vaccination, the presence of false positives for anti-HBs in patients undergoing infusion of blood products and escape mutations of the hepatitis B surface antigen (HBsAg) could explain this lack of efficacy. For this reason, it is recommended that vaccination protocols be implemented universally, along with the follow-up of the level of protection in patients with cirrhosis, adding prophylaxis with analogues when receiving a graft from an anti-HBc-positive donor. Clinical and serological surveillance alone can be considered for patients with anti-HBs levels greater than 200 mUI/mL after vaccination

Cholangitis and multiple liver abscesses after percutaneous ethanol injection (PEI) for recurrent hepatocellular carcinoma (HCC).

Percutaneous ablation procedures are minimally invasive treatments for unresectable early stage hepatocellular carcinoma (HCC). These techniques are usually safe, but rare and even fatal complications have been described. We present a fatal result after percutaneous ethanol injection (PEI) for the treatment of a recurrent HCC in a non-cirrhotic liver, with subsequent development of diffuse cholangitis and multiple liver abscesses. Although percutaneous drainage and intensive antibiotic treatment were employed, the patient finally died. We discuss about the etiology and the physiopathology of this rare complication in which the therapeutic options are limited and usually unsuccessful.

Cholangitis and multiple liver abscesses after percutaneous ethanol injection (PEI) for recurrent hepatocellular carcinoma (HCC) / Colangitis y abscesos hepáticos múltiples tras la inyección percutánea de etanol (IPE) en el tratamiento del carcinoma hepatocelular recurrente

Percutaneous ablation procedures are minimally invasive treatments for unresectable early stage hepatocellular carcinoma (HCC). These techniques are usually safe, but rare and even fatal complications have been described. We present a fatal result after percutaneous ethanol injection (PEI) for the treatment of a recurrent HCC in a non-cirrhotic liver, with subsequent development of diffuse cholangitis and multiple liver abscesses. Although percutaneous drainage and intensive antibiotic treatment were employed, the patient finally died. We discuss about the etiology and the physiopathology of this rare complication in which the therapeutic options are limited and usually unsuccessful(AU)

Estudios volumétricos y anatómicos en el donante vivo / No disponible

No disponible

Indicaciones actuales de tratamiento triple para la hepatitis C / Current indications for triple therapy in hepatitis C virus infection

Resumen La infección crónica por el virus de la hepatitis C (VHC) es la principal causa de cirrosis hepática y hepatocarcinoma en los países occidentales. Existe evidencia para afirmar que el aclaramiento del VHC inducido por la terapia antiviral proporciona beneficio con incremento de la supervivencia y disminución de las complicaciones derivadas de la cirrosis. La triple terapia con boceprevir o telaprevir asociados a interferón pegilado y ribavirina ha incrementado las tasas de respuesta viral sostenida tanto en pacientes no tratados previamente como en aquellos en los que ha fallado una pauta previa de tratamiento. El manejo del tratamiento con estas nuevas moléculas requiere familiarizarse con las indicaciones y pautas a emplear, así como con los eventos adversos y la monitorización del desarrollo de resistencias. Los objetivos fundamentales son una selección cuidadosa del paciente y del régimen terapéutico que se va a emplear, así como lograr una adherencia adecuada que permita obtener óptimos resultados de eficacia (AU)

Abstract Chronic hepatitis C virus (HCV) infection is the main cause of liver cirrhosis and liver carcinoma in western countries. There is evidence that HCV clearance induced by antiviral therapy is beneficial, increasing survival and reducing the complications of cirrhosis. Triple therapy with boceprevir or telaprevir associated with pegylated interferon and ribavirin has increased rates of sustained viral response both in treatment-naïve patients and in those failing previous regimens. Before treating patients with these new molecules, physicians should be familiar with their indications and the regimens to be used. Furthermore, both adverse events and the development of resistances must be monitored. The main aims are careful selection of patients and of the regimen to be used, and achieving adequate adherence to obtain optimal results (AU)

[Current indications for triple therapy in hepatitis C virus infection]. / Indicaciones actuales de tratamiento triple para la hepatitis C.

Chronic hepatitis C virus (HCV) infection is the main cause of liver cirrhosis and liver carcinoma in western countries. There is evidence that HCV clearance induced by antiviral therapy is beneficial, increasing survival and reducing the complications of cirrhosis. Triple therapy with boceprevir or telaprevir associated with pegylated interferon and ribavirin has increased rates of sustained viral response both in treatment-naïve patients and in those failing previous regimens. Before treating patients with these new molecules, physicians should be familiar with their indications and the regimens to be used. Furthermore, both adverse events and the development of resistances must be monitored. The main aims are careful selection of patients and of the regimen to be used, and achieving adequate adherence to obtain optimal results.