Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.

BACKGROUND: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis. METHODS: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan® <9.5 kPa and Fibrotest®  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). FINDINGS: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. INTERPRETATION: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks.

Food matrix and isoflavones bioavailability in early post menopausal women: a European clinical study.

The estrogenic effects of soy isoflavones (IF) on symptoms of menopause are of particular interest. The aim of the present study was to improve compliance of IF in two IF-enriched foods providing the same IF circulating levels in postmenopausal women. Forty-two healthy postmenopausal women (mean age: 53.28 years) were recruited for a randomized, crossover, multicenter trial conducted in the Netherlands, Italy and France. Over 18 days, volunteers were assigned to two groups and supplemented with two different IF-enriched foods (100 mg IF aglycones/two servings). The first group had to eat two biscuits daily for three days. After a wash-out period (11 d), they received cereal bars for three days. The second group started with the cereal bars and finished with biscuits. After IF intake, plasma and urinary levels of genistein, daidzein, O desmethyl angolensin and equol significantly increased and returned to baseline level after the washout period. There was no difference between biscuits and cereals bars intake, as shown by group values at each end of experimental period (day 4 or day 18). Both matrixes are comparable in terms of IF-circulating levels and could be used independently.

Isoflavone consumption does not increase the bone mass in osteopenic obese female zucker rats.

Some controversy exists in the literature concerning the effects of leptin on bone metabolism. Thus we have compared femoral bone density and biochemical markers of bone metabolism in male and female fatty (leptin-resistant) Zucker rats and their lean homozygous controls at 3 and 6 months of age. At 3 months, no differences concerning total, diaphyseal (cortical bone), and distal metaphyseal (trabecular bone) femoral bone densities, plasma osteocalcin concentrations, and urinary deoxypyridinoline excretion were observed between fatty and lean rats. On the opposite, at 6 months of age, in both males and females, total, diaphyseal, and distal metaphyseal femoral bone densities and plasma osteocalcin concentrations were lower in Zucker than in lean rats. Soybean isoflavone consumption (40 microg/g body weight/day for 90 days, a dose which prevents osteopenia following ovariectomy both in lean Zucker homozygous controls and in Wistar rats) by obese female Zucker rats had no significant effect upon their bone mass.