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Background Treatment of GT3 remains challenging compared to other genotypes. Aims To explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4). Methods Between May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics. Results Of 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04-19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58-47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64-18.95.96, P = 0.006). Conclusions Our real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).

Background and objectivesThe pangenotypic single tablet regimen of NS5B inhibitor sofobuvir (SOF) and NS5A inhibitor velpatasvir (VEL) is advised for 12 weeks in HCV-infected patients including those with compensated cirrhosis. Addition of ribavirin (RBV) may be considered in genotype 3 (GT3) with compensated and is recommended in decompensated cirrhosis. Real-life results with SOF/VEL are limited. To evaluate efficacy and safety in a large real-world-cohort including patients with different GTs and various fibrosis stages.DesignIn total, 1429 patients were treated with SOF/VEL 400/100 mg for 12 weeks in the Puglia registry between June 2017 and May 2018. 1319 (92.3%) reached week 12 post-treatment (SVR12) at the moment. Only 41 received RBV. Diagnosis of cirrhosis was based on transient elastography and/or APRI or FIB-4 scores. Sensitivity analysis in the population including all patients except non virological failure was conducted. Primary efficacy endpoint was the percentage of patients with SVR12.ResultsPatients' mean age was 63.8 years, 42.3% had GT1. The majority were naïve and 735 (55.5%) F0/F2. Of the remaining 587, 282 had cirrhosis. SVR12 was 98.5%, 98.0% in GT1, 99.4% in GT2, 97.1% in GT3, 100% in GT4. Overall, SVR12 by sensitivity analysis was 99.4%; 99.7% among F0-F1. Among 218 PWID, SVR12 was 94.5%. Discontinuation rates were 3.7% among PWID and 0.7% among non-PWID (p = 0.004).ConclusionsSOF/VEL treatment of chronic HCV infection reaches very high cure rates in a variety of patients; including those with F0/F1 and PWID.

BACKGROUND:Atherosclerosis is a complex multifactorial disease and the apolipoprotein E (APOE) polymorphism has been associated to vascular complications of atherosclerosis. OBJECTIVES:To investigate the relationship between the APOE genotypes and advanced peripheral vascular disease. MATERIALS AND METHODS:258 consecutive patients (201 males and 57 females, mean age 70.83 ± 7.89 years) with severe PVD were enrolled in a 42-months longitudinal study (mean 31.65 ± 21.11 months) for major adverse cardiovascular events. At follow-up genotypes of the APOE polymorphism were investigated in blinded fashion. RESULTS:As compared with ε3/ε3, in ε4-carriers a significant higher incidence of major adverse cardiovascular events (35.58% vs. 20.79%; p = 0.025) and total peripheral revascularization (22.64% vs. 5.06%; p < 0.001) was observed. Prospective analysis, showed that ε4-carriers have an increased hazard ratio for major adverse cardiovascular events (adjusted HR 1.829, 95% CI 1.017-3.287; p = 0.044) and total peripheral revascularization (adjusted HR = 5.916, 95% CI 2.405-14.554, p