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.

[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.