Efficacy of Sofosbuvir and Velpatasvir, With and Without Ribavirin, in Patients With Hepatitis C Virus Genotype 3 Infection and Cirrhosis.

BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51 ± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

Clinical Significance of Environmental Mycobacteria Isolated From Respiratory Specimens of Patients With and Without Silicosis.

OBJECTIVE: To describe the clinical, functional and radiographic differences of respiratory disease caused by environmental mycobacteria (EM) in patients with and without silicosis. METHOD: Retrospective, observational study in patients with nontuberculous mycobacteria isolated in the Hospital Meixoeiro (University Hospital of Vigo) microbiology laboratory between January 2007 and December 2013. Patients were grouped according to the presence or absence of silicosis and mycobacterial lung disease, using American Thoracic Society criteria. RESULTS: In 156 cases, at least one species of EM had been isolated from the respiratory culture. A total of 71% were identified in men, 40 (25.6%) of whom had silicosis. Sixty patients (38.5%) met American Thoracic Society microbiological criteria: 62.5% of the silicosis group and 30.2% of the non-silicosis group. The most common species were Mycobacterium avium complex, Mycobacterium genavense and Mycobacterium chelonae. American Thoracic Society criteria for environmental mycobacterial disease were met in 34 (22.7%) patients: 14 in the silicosis group and 20 in the non-silicosis group. Treatment was administered in 24 cases, with better bacteriological eradication levels in the non-silicosis group. CONCLUSIONS: In our series, a history of silicosis was related with a higher incidence of environmental mycobacterial disease. The causative species in the majority of cases in our setting was Mycobacterium avium complex, followed by Mycobacterium genavense. Patients with silicosis showed lower cure rates after treatment.

Regimenes antivirales basados en sofosbuvir: presente y futuro en hepatitis C / Sofosbuvir-based regimens: the present and future in hepatitis C treatment

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Significado clínico de las micobacterias ambientales aisladas en muestras respiratorias en pacientes con silicosis y sin silicosis / Clinical Significance of Environmental Mycobacteria Isolated From Respiratory Specimens of Patients With and Without Silicosis

Objetivo: Describir las diferencias clínicas, funcionales y radiográficas de la enfermedad respiratoria por micobacterias ambientales (MA) en pacientes con silicosis y sin silicosis. Método: Estudio observacional retrospectivo en pacientes a los que se les había aislado una micobacteria no tuberculosa en el laboratorio de Microbiología del hospital de O Meixoeiro (CHU de Vigo) desde enero 2007 hasta diciembre 2013. Se diferenció a los pacientes según presentaran o no silicosis y enfermedad pulmonar por MA utilizando los criterios de la American Thoracic Society. Resultados: Se identificaron 156 casos con aislamiento respiratorio de al menos una especie de MA. El 71% eran varones, de los cuales 40 (25,6%) tenían silicosis. En 60 pacientes (38,5%), el 62,5% del grupo de silicosis y el 30,2% del grupo sin silicosis, se cumplían los criterios microbiológicos recomendados por la American Thoracic Society siendo las especies más comunes Mycobacterium avium complex, Mycobacterium genavense y Mycobacterium chelonae. En 34 pacientes (22,7%), 14 del grupo de silicosis y 20 del grupo sin silicosis, se cumplían los criterios de la American Thoracic Society de enfermedad pulmonar por MA. Se realizó tratamiento en 24 casos, con mayores niveles de erradicación bacteriológica en el grupo sin silicosis. Conclusiones: En nuestros pacientes el antecedente de silicosis se relacionó con mayor incidencia de enfermedad por MA. La especie causante de la mayor parte de los casos de de enfermedad en nuestro medio por MA es Mycobacterium avium complex, seguido de Mycobacterium genavense. Los pacientes con silicosis presentaron menores niveles de curación tras el tratamiento

Objective: To describe the clinical, functional and radiographic differences of respiratory disease caused by environmental mycobacteria (EM) in patients with and without silicosis. Method: Retrospective, observational study in patients with nontuberculous mycobacteria isolated in the Hospital Meixoeiro (University Hospital of Vigo) microbiology laboratory between January 2007 and December 2013. Patients were grouped according to the presence or absence of silicosis and mycobacterial lung disease, using American Thoracic Society criteria. Results: In 156 cases, at least one species of EM had been isolated from the respiratory culture. A total of 71% were identified in men, 40 (25.6%) of whom had silicosis. Sixty patients (38.5%) met American Thoracic Society microbiological criteria: 62.5% of the silicosis group and 30.2% of the non-silicosis group. The most common species were Mycobacterium avium complex, Mycobacterium genavense and Mycobacterium chelonae. American Thoracic Society criteria for environmental mycobacterial disease were met in 34 (22.7%) patients: 14 in the silicosis group and 20 in the non-silicosis group. Treatment was administered in 24 cases, with better bacteriological eradication levels in the non-silicosis group. Conclusions: In our series, a history of silicosis was related with a higher incidence of environmental mycobacterial disease. The causative species in the majority of cases in our setting wasMycobacterium avium complex, followed by Mycobacterium genavense. Patients with silicosis showed lower cure rates after treatment

Patología orgánica en adicciones: otras infecciones asociadas al consumo de drogas / Organic pathology in addictions: other infections associated with drugs dependence

Las infecciones constituyen una de las complicaciones mas graves asociadas al uso de drogas. Los drogadictos además de la adquisición del virus de la inmunodeficiencia humana (VIH) y de las hepatitis virales, están en riesgo de adquirir una amplia variedad de infecciones bacterianas y enfermedades de transmisión sexual. La mayoría de las infecciones que adquieren los adictos a drogas por vía parenteral, se producen por la flora comensal del propio individuo o por microorganismos que contaminan la droga, los adulterantes, o la parafernalia utilizada. La presencia de fiebre en esta población constituye un desafió diagnostico, por lo que se esquematiza el abordaje de este cuadro. Las infecciones cutáneas y de partes blandas, las infecciones óseas y articulares, la afectación ocular, las infecciones intravasculares especialmente la endocarditis, las infecciones pulmonares con inclusión de la tuberculosis, las enfermedades de transmisión sexual, y otras de menor relevancia como el tétanos, botulismo y paludismo constituyen las principales infecciones asociadas a la drogadicción parenteral. En el presente trabajo se ofrece una revisión dirigida a aquellas personas que ven o no con frecuencia infecciones en el colectivo de adictos, y se resume la información mas reciente sobre las infecciones bacterianas asociadas con el uso de drogas por vía intravenosa. Además se analiza la patogenia de las infecciones en este colectivo y el manejo del paciente adicto a drogas por vía parenteral que consulta por fiebre

The infections constitute one of the complications more serious associated to the use of drugs. The injection drug user besides the acquisition of the virus of the human (HIV) immunodeficiency and of the viral hepatitis, they are in risk of acquiring to comprehensive variety of bacterial infections and illnesses of sexual transmission. Most of the infections that the addicts acquire to drugs for via parenteral, they take place for the own individual's flora commensal or for microorganisms that infect the drug, the adulterants, or the used paraphernalia. The presence of fever in this population constitutes a challenge diagnosis, for what the boarding of this bolster is schematized. The skin and soft tissue infections, the bone and joint infections, the eye infections, the intravascular infections especially the endocarditis, the lung infections with inclusion of the tuberculosis, the illnesses of sexual transmission, and others of smaller relevance like the tetanus, botulism and paludism constitute the main infections associated to the parenteral drug abuses. This article reviews the infections among IV drug users, and summarizes the most recent information on bacterial infections associated to the use of IV drugs. Pathogenetic mechanisms are analysed, as well as the management of Intravenous Drug Users patients presenting with fever