Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen.

OBJECTIVES: To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. METHODS: Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. RESULTS: We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. CONCLUSIONS: One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.

Prospective validation of two models for ultrasonographic diagnosis of cirrhosis.

OBJECTIVE: To perform a prospective validation and comparative analysis of two ultrasonographic diagnostic scores of cirrhosis in patients with silent liver disease. DESIGN: cross-sectional study, prospective and blind. ROC curves evaluated the diagnostic utility of: a) Bologna score (BS): assessment of liver surface nodularity and portal flow velocity, and b) Cadiz score (CS): assessment of liver echo structure, portal vein caliber and spleen area. Liver biopsy was considered the gold standard for the diagnosis of cirrhosis. PATIENTS: One hundred and thirteen patients, 76 men and 37 women, mean age 44 years old (range 18-73 years) referred for evaluation of chronic liver disease without clinical or biochemical evidence of advanced disease (absence of jaundice, ascites, encephalopathy, malnutrition or coagulopathy). RESULTS: Cirrhosis was diagnosed in 25 patients (22.1%). BS: sensitivity 84%, specificity 79.5%, area under the ROC curve 86.7%. CS: sensitivity 84%, specificity 89.8%, area under the ROC curve 92.4%. Portal vein was not displayed in 7 patients(6%) and portal flow velocity was not recorded in 13 (11.5%). These results agree with those obtained in the original articles developing both scores. There were no statistically significant differences between the two scores. Specificity reached 97% with joint use of both models, but sensitivity decreased to 72%. CONCLUSIONS: Presence or absence of cirrhosis in patients with silent liver disease can be established by Doppler ultrasound with high diagnostic accuracy. The joint use of both scores has high diagnostic specificity. Both diagnostic models are highly re-producible.

Validación prospectiva de dos modelos de diagnóstico de cirrosis hepática mediante ultrasonografía / Prospective validation of two models for ultrasonographic diagnosis of cirrhosis

Objetivo: realizar una validación prospectiva y un análisis comparativo de dos escalas de diagnóstico ecográfico de cirrosis en pacientes con enfermedad hepática silente. Diseño experimental: estudio transversal, prospectivo y ciego. Mediante curvas ROC se evaluó la utilidad diagnóstica de: a) escala de Bolonia (EB): valoración de la nodularidad de la superficie hepática y la velocidad de flujo portal; y b) escala de Cádiz (EC): valoración de la ecoestructura hepática, calibre portal y área esplénica. La biopsia hepática se consideró el estándar para el diagnóstico de cirrosis. Pacientes: ciento trece pacientes, 76 varones y 37 mujeres con edad media de 44 años (18-73) remitidos para estudio de una hepatopatía crónica sin indicios clínicos ni bioquímicos de enfermedad avanzada (ausencia de ictericia, ascitis, encefalopatía, malnutrición ni coagulopatía, actuales ni previas). Resultados: veinticinco pacientes (22,1%) fueron diagnosticados de cirrosis. EB: sensibilidad 84%, especificidad 79,5%, área bajo la curva ROC 86,7%. EC: sensibilidad 84%, especificidad 89,8%, área bajo la curva ROC 92,4%. La vena porta no se visualizó en 7 pacientes (6%) y la velocidad de flujo portal no se determinó en 13 (11,5%). Estos resultados son superponibles a los obtenidos en los artículos originales. No se encontraron diferencias estadísticamente significativas entre ambas escalas. El empleo conjunto de los dos modelos incrementó la especificidad diagnóstica hasta el 97% con una sensibilidad del 72%. Conclusiones: la presencia o ausencia de cirrosis en pacientes con enfermedad hepática silente puede ser establecida mediante ecografía con una elevada precisión diagnóstica. El empleo conjunto de ambas escalas alcanza una elevada especificidad diagnóstica. La reproducibilidad de ambas escalas es excelente(AU)

Objective: to perform a prospective validation and comparative analysis of two ultrasonographic diagnostic scores of cirrhosis in patients with silent liver disease. Design: cross-sectional study, prospective and blind. ROC curves evaluated the diagnostic utility of: a) Bologna score (BS): assessment of liver surface nodularity and portal flow velocity, and b) Cadiz score (CS): assessment of liver echostructure, portal vein caliber and spleen area. Liver biopsy was considered the gold standard for the diagnosis of cirrhosis. Patients: one hundred and thirteen patients, 76 men and 37 women, mean age 44 years old (range 18-73 years) referred for evaluation of chronic liver disease without clinical or biochemi - cal evidence of advanced disease (absence of jaundice, ascites, encephalopathy, malnutrition or coagulopathy) . Results: cirrhosis was diagnosed in 25 patients (22.1%). BS: sensitivity 84%, specificity 79.5%, area under the ROC curve 86.7%. CS: sensitivity 84%, specificity 89.8%, area under the ROC curve 92.4%. Portal vein was not displayed in 7 patients (6%) and portal flow velocity was not recorded in 13 (11.5%). These results agree with those obtained in the original articles developing both scores. There were no statistically significant differences between the two scores. Specificity reached 97% with joint use of both models, but sensitivity decreased to 72%. Conclusions: presence or absence of cirrhosis in patients with silent liver disease can be established by Doppler ultrasound with high diagnostic accuracy. The joint use of both scores has high diagnostic specificity. Both diagnostic models are highly reproducible(AU)

[Effectiveness of percutaneous drainage in the treatment of abdominal fluid collections in inflammatory pancreatic disease]. / Efectividad del drenaje percutáneo en el tratamiento de las colecciones abdominales asociadas con una enfermedad inflamatoria del páncreas.

AIMS: To assess the effectiveness of ultrasonography-guided percutaneous drainage (UGPD) in the management of fluid collections (FC) in acute and chronic pancreatitis, and to evaluate factors associated with treatment results. METHOD: Seventy-two patients with pancreatic fluid collections ranging from 5 to 20 cm (median 9 cm) were studied. There were 27 type I pseudocysts (PC), 12 type II PC, 13 type III PC, 16 abscesses, and 4 acute fluid collections. Catheters were placed in 60 patients and simple aspiration was performed in 8 patients. UGPD could not be performed in 4 patients. RESULTS: UGPD was curative in 39 patients (54.1%): 44.4% in type I PC, 83% in type II PC, 30.7% in type III PC, 62.5% in abscesses, and 75% in acute FC. Resolution was achieved in 35.7% of patients with pancreatic duct communication and in 71.4% of those with non-communicated FC. No differences in effectiveness were observed according to the etiology of pancreatitis, pancreatic duct obstruction, drainage method, or the number or size of FC. UGPD was effective in 45.8% of the procedures performed before 1993, in 58.3% of those performed between 1993 and 1999, and in 63.6% of those performed after 2000. The complication rate was 37.5% and all complications were mild. CONCLUSIONS: UGPD is an effective treatment for pancreatic FC. The effectiveness of this method depends on appropriate patient selection and careful management of acute pancreatitis. Outcomes were less favorable in patients with type III PC and in those with duct communication.

Efectividad del drenaje percutáneo en el tratamiento de las colecciones abdominales asociadas con una enfermedad inflamatoria del páncreas / Effectiveness of percutaneous drainage in the treatment of abdominal fluid collections in inflammatory pancreatic disease

Objetivos: Evaluar la efectividad del drenaje percutáneo (DP) guiado por ecografía en el tratamiento de las colecciones asociadas a pancreatitis y la existencia de factores determinantes de la utilidad de dicho tratamiento. Método: 72 pacientes con colecciones pancreáticas de 5-20 cm (mediana, 9 cm): 27 seudoquistes (SQ) tipo I, 12 tipo II y 13 tipo III, 16 abscesos y 4 colecciones agudas. Sesenta pacientes fueron tratados mediante la colocación de catéteres y 8 mediante aspiración simple. En 4 no se consiguió el DP. Resultados: En 39 casos (54,1%), el DP fue curativo: el 44,4% de los SQ tipo I, el 83% de los tipo II, el 30,7% de los tipo III, el 62,5% de los abscesos pancreáticos, el 75% de las colecciones agudas, el 35,7% de las comunicadas con el conducto pancreático y el 71,4% de las no comunicadas. No se observaron diferencias en función de la etiología de la pancreatitis, la presencia de obstrucción ductal, la técnica de drenaje, el número de colecciones ni el tamaño de éstas. El DP fue resolutivo en el 45,8% de los realizados antes de 1993, en el 58,3% de los llevados a cabo entre 1993 y 1999 y en el 63,6% de los realizados desde el año 2000. Se registró un 37,5% de complicaciones, todas leves. Conclusiones: El DP es una alternativa útil en el tratamiento de las colecciones asociadas a una enfermedad pancreática, cuya efectividad depende de una correcta selección de los pacientes y de una cuidadosa atención a las medidas asociadas al tratamiento de la pancreatitis aguda. Cabe esperar peores resultados en pacientes con SQ tipo III y otros comunicados con el conducto pancreático

Aims: To assess the effectiveness of ultrasonography-guided percutaneous drainage (UGPD) in the management of fluid collections (FC) in acute and chronic pancreatitis, and to evaluate factors associated with treatment results. Method: Seventy-two patients with pancreatic fluid collections ranging from 5 to 20 cm (median 9 cm) were studied. There were 27 type I pseudocysts (PC), 12 type II PC, 13 type III PC, 16 abscesses, and 4 acute fluid collections. Catheters were placed in 60 patients and simple aspiration was performed in 8 patients. UGPD could not be performed in 4 patients. Results: UGPD was curative in 39 patients (54.1%): 44.4% in type I PC, 83% in type II PC, 30.7% in type III PC, 62.5% in abscesses, and 75% in acute FC. Resolution was achieved in 35.7% of patients with pancreatic duct communication and in 71.4% of those with non-communicated FC. No differences in effectiveness were observed according to the etiology of pancreatitis, pancreatic duct obstruction, drainage method, or the number or size of FC. UGPD was effective in 45.8% of the procedures performed before 1993, in 58.3% of those performed between 1993 and 1999, and in 63.6% of those performed after 2000. The complication rate was 37.5% and all complications were mild. Conclusions: UGPD is an effective treatment for pancreatic FC. The effectiveness of this method depends on appropriate patient selection and careful management of acute pancreatitis. Outcomes were less favorable in patients with type III PC and in those with duct communication

Ecografía Doppler renal y su relación con la función renal en pacientes con cirrosis hepática / Renal Doppler ultrasonography and its relationship with the renal function in patients with liver cirrhosis

FUNDAMENTO: Relacionar los cambios hemodinámicos renales, valorados por ecografía Doppler, con el desarrollo de ascitis, función renal y sistemas vasoactivos endógenos en pacientes con cirrosis hepática. PACIENTES Y MÉTODO: Se estudiaron de formas prospectiva 60 pacientes cirróticos, 31 compensados y 29 con ascitis. Se determinaron el índice de resistencia renal, la función renal y los valores plasmáticos de actividad de renina, aldosterona, noradrenalina y hormona antidiurética. RESULTADOS: El índice de resistencia renal fue significativamente superior en los pacientes cirróticos con ascitis (0,68) que en los cirróticos compensados (0,63) y se correlacionó significativamente con las concentraciones séricas de creatinina, excreción urinaria de sodio, actividad de renina plasmática y concentración plasmática de aldosterona. CONCLUSIONES: El índice de resistencia renal, determinado por ecografía Doppler, se eleva progresivamente con la evolución de la cirrosis hepática, con el empeoramiento de la función renal y con la activación de los sistemas vasoactivos endógenos (AU)