Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of Rapanea ferruginea

Juarana Dal Mas,1 Tailyn Zermiani,1 Liliani C Thiesen,1 Joana LM Silveira,2 Kathryn ABS da Silva,1 Márcia M de Souza,1 Angela Malheiros,1 Tania MB Bresolin,1 Ruth M Lucinda-Silva1 1NIQFAR, Graduate Program in Pharmaceutical Sciences, University of Vale do Itajaí, Itajaí, Santa Catarina, Brazil; 2Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, Brazil Abstract: The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88±8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was -34.7±1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10±0.08 and 53.03 µg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity. Keywords: nanotechnology, nanoemulsion, Rapanea ferruginea, anti-inflammatory, phytomedicin

Anti-phospholipid antibody prevalence and association with subclinical atherosclerosis and atherothrombosis in the general population

Background: There is no agreement on the prevalence of anti-phospholipid antibodies (aPLs) and the correlation with atherosclerosis and cardiovascular (CV) events in the general population. Methods: We performed a cross-sectional study on 1712 randomly enrolled subjects from a Northern Italian city to investigate the presence of aPLs and the association with subclinical atherosclerosis (using the carotid artery intima media thickness measured as inter-adventitia common carotid artery diameters - ICCAD) and retrospectively collected CV factors and events (i.e. acute myocardial infarction, stroke, and peripheral obliterans arterial vasculopathy) using physician-assisted questionnaires. We tested serum IgG, IgM, and IgA anti-cardiolipin, anti-beta2glycoprotein I (aGPI), and anti-phosphatidylserine-prothrombin antibodies. Results: Positive aPLs were found in 15.1% of the subjects, with no differences between sex but with higher rates in older subjects. Carotid subclinical atherosclerosis was more frequent in aPL positive subjects; more specifically, aGPI IgA were associated with higher ICCAD average (adjusted beta 0.51, 95% confidence interval (CI)0.17–0.84; p = 0.003). A positive history of CV events was also more frequent in aPL positive subjects (odds ratio (OR) 1.67, 95%CI 1.08–2.54; p = 0.012), particularly peripheral obliterans arterial vasculopathy (OR 2.02; 95%CI 1.14–3.57; p = 0.015). Among subjects with a Framingham risk score >20, and/or diabetes, and/or body mass index >35 kg/m2, aPL positivity was associated to the highest risk of CV events (OR 2.52, 95%CI 1.24–5.11; p = 0.011). Conclusions: APL prevalence in the general population is higher than previously reported. CV events and subclinical atherosclerosis are more frequent in the presence of aPL, particularly when a high CV risk coexists

High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting

In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n = 168, 46%) and 3 (n = 59, 16.2%). DAA was discontinued a median of 1 (IQR 1–4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2 weeks before the planned schedule. In patients with F0–F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n = 2/4) vs. 99.1% (n = 109/110) for ≥4 weeks, p = 0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) for ≥8 weeks, p = 0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real-life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0–F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials