Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring" in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease

Acúmulo e formas de cobre e zinco no solo após aplicações sucessivas de dejeto líquido de suínos

As aplicações sucessivas de dejeto líquido de suínos no solo podem aumentar os teores e alterar as formas de Cu e Zn no solo. O presente trabalho teve como objetivo estimar o acúmulo de Cu e Zn e suas formas em solo submetido a aplicações sucessivas de dejeto líquido de suínos, em sistema plantio direto com rotação de culturas. O trabalho foi desenvolvido em um Argissolo Vermelho distrófico arênico na área experimental do Departamento de Engenharia Agrícola da Universidade Federal de Santa Maria (RS). Os tratamentos consistiram na aplicação de 0, 20, 40 e 80 m³ ha-1 de dejeto líquido de suínos. Foram realizadas 17 aplicações de dejetos de maio de 2000 até o momento da coleta do solo, em outubro de 2006. Amostras de solo foram coletadas nas camadas de 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-25, 25-30, 30-35, 35-40, 40-50 e 50-60 cm, secas ao ar, passadas em peneiras de 2 mm e moídas em grau de ágata. Em seguida, foram preparadas e analisados os teores pseudototais após extração pelo método 3050B da EPA, disponíveis por meio da extração com HCl 0,1 mol L-1, além do fracionamento químico do Cu e do Zn. Nos dejetos de suínos foram determinados os teores pseudototais de Cu e Zn. As aplicações sucessivas de dejeto líquido de suínos no solo aumentaram os teores de Cu e Zn das camadas superficiais, com migração até 12 e 10 cm de profundidade, respectivamente. O Cu e Zn adicionados são acumulados no solo em formas biodisponíveis, sendo preferencialmente ligados às frações orgânica e mineral, respectivamente.Successive applications of pig slurry in the soil can increase the levels and change the forms of copper (Cu) and zinc (Zn). The objective of this study was to evaluate Cu and Zn accumulation and forms in the soil of areas with successive pig slurry applications under no tillage crop rotation. The experiment was carried out in a Typic Hapludalf in the experimental area of the Department of Agricultural Engineering of the Federal University of Santa Maria, Santa Maria (RS), Brazil. Pig slurry was applied at rates of 0, 20, 40 and 80 m³ ha-1. A total of 17 applications were applied to the soil surface between May 2000 and October 2006. The soil samples were collected in the layers 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-25, 25-30, 30-35, 35-40, 40-50, and 50-60 cm. The soil was dried, ground, sieved (2 mm) and the pseudo-total levels, available (HCl 0.1 mol L-1) and chemical fractions of Cu and Zn were determined. The pseudo-total contents of copper and zinc in the slurry were analyzed. Successive applications of pig slurry increased the pseudo-total content of copper and zinc in soil (surface layers), with migration to 12 and 10 cm depths, respectively. The Cu and Zn applied were accumulated in the soil in bioavailable forms, and preferentially associated with the organic and mineral fraction, respectively

FATTY LIVER AND GUT MICROBIOTA: A NEW MULTI-DIMENSIONAL APPROACH FOR PERSONALIZED PREVENTIVE MEDICINE

Cardiovascular, degenerative, hepato-digestive, metabolic and neoplastic diseases are major causes of death; all of them are beckoned years before by fatty liver that can quantify by non-invasive ultrasound methods. Such a measure is sensitive and reproducible and qualifies as mirror of general health to monitor the efficacy of preventive care in pre-symptomatic subjects. One major determinant of alimentary and general health is the gut microbiota that regulates hepatic gene expression, lipid metabolism and contributes to hepatic inflammation and obesity. The microbiota can be dynamically modified by probiotic/ prebiotic supplementation, however a direct gut microbiota profiling by stool metagenomics is limited by sampling error. The study of blood and/or saliva metabolites (metabolomics) and circulating antimicrobial antibodies provide an indirect microbiota profiling. Studies need to be performed to test whether variation of metabolomics and antimicrobial antibody levels correlate with the in vivo bacteria dynamics. The non-invasive measure of fatty liver in combination with of the gut microbiota characterization by metagenomics, metabolomics and anti-microbial enzyme immune assays will provide an innovative technological approach to stratify individuals with fatty liver for both prevention, outcome prediction and personalized treatment and to identify new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets</jats:p